Fall 2013 by McMahon Group

Bridging the gap between the hospital and alternate-site care Volume 2 • Number 4 • Fall 2013 • specialtypharmacycontinuum.com

In This Issue 30-Minute Interview

McKesson’s Douglas Moeller on the power of informatics in cost containment.

Affordable Care Act:

Expect It To Expand Specialty’s Inﬂuence

Policy

A bioethicist’s view on the ethical hazards of high-cost drugs.

2012 spending trend stayed low, but pressure is building.

Another Move Into Specialty From Hospitals UHC, a network of 116 nonprofit academic medical center and 298 affiliated hospital members, announced that it will launch a program by late 2013 or early 2014 to help those facilities gain access to limited distribution specialty medications and contracts. To be eligible, UHC members will need to sign a letter stating they will adhere to care protocols and guidelines being established by UHC to ensure consistent system-wide conformance to specialty pharmacy quality standards, according to Jake Groenewold, MBA, the senior vice

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Technology

IVIG FAQ: Can IVIG cause aseptic meningitis?

Educational Review

A hassle for health systems?

Smartphone apps, remote monitoring: “waves of the present.”

Clinical

Ensuring Temperature Integrity of Specialty Drugs

San Antonio—The specialty pharmacy industry will be front and center in the transition to a health care system shaped by the Affordable Care Act (ACA), experts believe. Speaking at the National Association of Specialty Pharmacy’s (NASP) Strategic Business Exchange, David Calabrese, RPh, MHP, the vice president and chief pharmacy officer at Catamaran, in Lisle, Ill., said that as forecasted spending on specialty drugs starts to exceed what is currently allocated to traditional medications, specialty pharmacies will be expected to help get the most out of a health care dollar. “Specialty pharmacy is a key area of focus across the board for all health care systems and stakeholders,” Mr. Calabrese told NASP attendees. He said specialty pharmacies need a “comprehensive and well-rounded set of strategies to ensure appropriate use and ensure patients gain the most value out of these drugs.”

What manufacturers look for when designing pharmacy networks.

‘White Bagging’ Of SP Medications Draws Some Ire

Mr. Calabrese said the payment reform portion of the ACA is shifting more financial risk onto providers, payors and health systems as they are reimbursed based on metrics of quality and cost-efficiency. Because specialty drugs are one of the fastest and most consistently growing portions of spending, specialty pharmacies will be called on to play a more involved role in managing patients and costs, he said. Management will include services already in place, such as disease and medication

Boston—With the growing number of patients using specialty pharmacy medications, hospitals and clinics face serious challenges from the practice of “white bagging,” where a specialty pharmacy delivers the product directly to a clinic or practice for use by a specific patient. Stakeholders say the practice can result in the loss of a significant amount of potential revenue for an institution, not to mention the operational hassles it can cause. “Health care systems that are not participating in specialty pharmacy are caught in a funnel of missed opportunities, where profit leaks from a health care system,” said Jim Smeeding, RPh, MBA,

see AFFORDABLE CARE, page 5

see WHITE BAGGING, page 9

Expect More Responsibility

Operations & Mgmt

see HOSPITALS, page 25

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FDA Watch Perjeta approved for breast cancer.

Stelara, Cimzia approved for psoriatic arthritis.

See page 26.

Evidence based. Patient proven.

Product Features FDA approved indications1 : s Chronic inﬂammatory demyelinating polyneuropathy (CIDP) s Primary immunodeﬁciency (PI) for both IV and SC administration s Idiopathic thrombocytopenic purpura (ITP)

Product properties1 : s No sugar s Optimal pH of: (4.0-4.5) s IgA content: average of 46μg/mL s Only trace amounts of sodium s Close to physiologic osmolality: (258 mOsm/kg)

Easy to use1 : s Latex-free packaging s Tamper-evident vials (cap overwrap) s Vials available in 1, 2.5, 5, 10, and 20 g s Long 3-year shelf life; room temperature storage* * Up to 6 months at any time during 36-month shelf life.

Important Safety Information Gamunex-C, Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified, is indicated for the treatment of primary humoral immunodeficiency disease (PI), idiopathic thrombocytopenic purpura (ITP), and chronic inflammatory demyelinating polyneuropathy (CIDP). Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin intravenous (IGIV) products in predisposed patients. Patients predisposed to renal dysfunction include those with any degree of preexisting renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. Gamunex-C does not contain sucrose. For patients at risk of renal dysfunction or failure, administer Gamunex-C at the minimum concentration available and the minimum infusion rate practicable. Gamunex-C is contraindicated in individuals with acute severe hypersensitivity reactions to Immune Globulin (Human). It is contraindicated in IgA deficient patients with antibodies against IgA and history of hypersensitivity. Gamunex-C is not approved for subcutaneous use in patients with ITP or CIDP. Due to the potential risk of hematoma formation, Gamunex-C should not be administered subcutaneously in patients with ITP. Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IGIV therapy. Thrombotic events have been reported in association with IGIV. Patients at risk for thrombotic events may include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization and/or known or suspected hyperviscosity. There have been reports of noncardiogenic pulmonary edema [Transfusion-Related Acute Lung Injury (TRALI)], hemolytic anemia, and aseptic meningitis in patients administered with IGIV. The high dose regimen (1g/kg x 1-2 days) is not recommended for individuals with expanded fluid volumes or where fluid volume may be a concern. Gamunex-C is made from human plasma. Because this product is made from human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. After infusion of IgG, the transitory rise of the various passively transferred antibodies in the patient’s blood may yield positive serological testing results, with the potential for misleading interpretation. In clinical studies, the most common adverse reactions with Gamunex-C were headache, fever, chills, hypertension, rash, nausea, and asthenia (in CIDP); headache, cough, injection site reaction, nausea, pharyngitis, and urticaria with intravenous use (in PI) and infusion site reactions, headache, fatigue, arthralgia and pyrexia with subcutaneous use (in PI); and headache, vomiting, fever, nausea, back pain, and rash (in ITP). The most serious adverse reactions in clinical studies were pulmonary embolism (PE) in one subject with a history of PE (in CIDP), an exacerbation of autoimmune pure red cell aplasia in one subject (in PI), and myocarditis in one subject that occurred 50 days post-study-drug infusion and was not considered drug related (in ITP). Please see adjacent page for brief summary of Gamunex-C full prescribing information. 1. GAMUNEX-C package insert. Research Triangle Park, NC: Grifols Therapeutics Inc.; 2010.

For more information: Grifols, Inc. Customer Service: 888 325 8579 Fax: 323 441 7968

Grifols, Inc. 5555 Valley Boulevard, Los Angeles, 90032 CA - USA Tel. 888-GRIFOLS (888 474 3657) www.grifolsusa.com

Printed in USA.

September 2012

GX116-0912

GAMUNEX® X®-C

• Thrombotic events have occurred in patients receiving IGIV therapy. Monitor patients with known risk factors for thrombotic events; consider baseline assessment of blood viscosity for Immune Globulin Injection (Human) 10% those at risk of hyperviscosity.

Caprylate/Chromatography Puriﬁed

• Aseptic Meningitis Syndrome (AMS) has been reported with GAMUNEX-C and other IGIV treatments, especially with high doses or rapid infusion.

HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to • Hemolytic anemia can develop subsequent to IGIV therapy due use GAMUNEX®-C safely and effectively. See full prescribing to enhanced RBC sequestration. Monitor patients for hemolysis information for GAMUNEX-C. and hemolytic anemia. GAMUNEX-C, [Immune Globulin Injection (Human) 10% • Monitor patients for pulmonary adverse reactions (transfusionCaprylate/Chromatography Puriﬁed] related acute lung injury [TRALI]). Initial U.S. Approval: 2003 • Volume overload WARNING: ACUTE RENAL DYSFUNCTION and FAILURE See full prescribing information for complete boxed warning. • Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin intravenous (IGIV) products in predisposed patients. • Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. GAMUNEX-C does not contain sucrose. • For patients at risk of renal dysfunction or failure, administer GAMUNEX-C at the minimum concentration available and the minimum infusion rate practicable.

• GAMUNEX-C is made from human plasma and may contain infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease agent. • Passive transfer of antibodies may confound serologic testing. ----------------------------ADVERSE REACTIONS---------------------------• PI – The most common adverse reactions (ⱖ5%) with intravenous use of GAMUNEX-C were headache, cough, injection site reaction, nausea, pharyngitis and urticaria. The most common adverse reactions (ⱖ5%) with subcutaneous use of GAMUNEX-C were infusion site reactions, headache, fatigue, arthralgia and pyrexia.

• ITP – The most common adverse reactions during clinical trials (reported in ⱖ5% of subjects) were headache, vomiting, fever, -------------------------INDICATIONS AND USAGE------------------------nausea, back pain and rash. GAMUNEX-C is an immune globulin injection (human) 10% liquid • CIDP – The most common adverse reactions during clinical indicated for treatment of: trials (reported in ⱖ5% of subjects) were headache, fever, chills, hypertension, rash, nausea and asthenia. • Primary Humoral Immunodeficiency (PI) To report SUSPECTED ADVERSE REACTIONS, contact Talecris • Idiopathic Thrombocytopenic Purpura (ITP) Biotherapeutics, Inc. at 1-800-520-2807 or FDA at • Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) 1-800-FDA-1088 or www.fda.gov/medwatch. ----------------------------CONTRAINDICATIONS-------------------------------------------------------DRUG INTERACTIONS---------------------------• Anaphylactic or severe systemic reactions to human • The passive transfer of antibodies may transiently interfere with immunoglobulin the response to live viral vaccines, such as measles, mumps • IgA deficient patients with antibodies against IgA and a history and rubella. Passive transfer of antibodies may confound of hypersensitivity serologic testing. ---------------------WARNINGS AND PRECAUTIONS--------------------• IgA deficient patients with antibodies against IgA are at greater risk of developing severe hypersensitivity and anaphylactic reactions. Have epinephrine available immediately to treat any acute severe hypersensitivity reactions. • Monitor renal function, including blood urea nitrogen, serum creatinine, and urine output in patients at risk of developing acute renal failure. • GAMUNEX-C is not approved for subcutaneous use in ITP patients. Due to a potential risk of hematoma formation, do not administer GAMUNEX-C subcutaneously in patients with ITP. • Hyperproteinemia, with resultant changes in serum viscosity and electrolyte imbalances may occur in patients receiving IGIV therapy.

--------------------USE IN SPECIFIC POPULATIONS -------------------• Pregnancy: no human or animal data. Use only if clearly needed. • Geriatric: In patients over 65 years of age do not exceed the recommended dose, and infuse GAMUNEX-C at the minimum infusion rate practicable.

Talecris Biotherapeutics, Inc. Research Triangle Park, NC 27709 USA U.S. License No. 1716

08939771/08939782-BS Revised: October 2010

Specialty Pharmacy Continuum • Fall 2013

THE 30-MINUTE INTERVIEW

Douglas Moeller, MD

Balancing Cost and Outomes Using IT Strategies Dr. Douglas Moeller, medical director of McKesson Health Solutions, discusses how his early years as an internist shaped his approach to cost management today, and why he feels medical informatics is one of the most important tools for detecting and then taking waste out of the clinical care equation.

Q: You bring the perspective of a physician to managed care. How has that played out?

A: I was in clinical practice for about 13 years before I migrated into managed care and medical informatics in various health care settings. Then I came to McKesson, and I’ve been here for about a decade, working on software technology that does indeed give me the opportunity to draw on my clinical and managed care background and apply both to cost-containment. What we’re primarily focused on is whether people have the data they need to make correct decisions regarding drug utilization, policy management, step-therapy recommendations and so on. It’s not up to us to dictate those decisions or to say there is a right way and a wrong way; rather, do

our end-users have enough information to be thoughtful in their determinations? It’s been fascinating to me to be an advocate for good decisions and good quality and to try to take the waste out of medication therapy, which is one of our primary tactics in developing tools that our clients can use to manage costs. Q: Medical informatics sounds like a new trend, but it’s been around for some time. Have you always had a strong interest in it?

A: Absolutely. I was using physician order entry when I was an intern in the early 1980s; we had one of the early light-pen systems and I ordered about 98% of my medications online. Here we are nearly 30 years later and we’re still pushing for more widespread

adoption of e-prescribing. After all that time, why can’t we get this done? It’s hard to fathom. Still, I’m optimistic, in part because I saw firsthand as a physician the potential benefits of informatics. Because of that experience, I always knew I needed to be attached to electronic systems that help us do our work better, and I think analytics is the “secret sauce” in any solution for thoughtful care management. Q: Do you have some real-world examples of how analytics—or the lack thereof—can affect efforts to improve care and control costs?

A: I used to practice with a core group of six general internists, and at one point we tried to look at our hypertension management efforts for some clues as to how we were doing. Well, it turned out that the frequency and intensity of patient visits, the number of drugs we prescribed, the number of lab tests we ordered and our patients’ actual blood pressure control had almost nothing to do with each other. That was my first inkling that I didn’t really know what my partners were doing, and that was because we did not have explicit, comparative feedback on our own patient care habits or results. Sure, we all went

to Grand Rounds and had access to the same educational material, and so we thought we assumed we all were following the same general care plan. But when you actually look at and measure physician behavior, it turns out that there is quite significant variation. And I found then, as I still do today, that if you present physicians with this type of information, in a non-accusatory or non-critical way, they actually see it as a problem—they’ll say, wow, this is not okay; I need to do better. And they will work hard to fix it. Q: I see how that can work on a small scale. But how about large payors and providers?

A: A number of health plans have struggled with the fact that it is indeed hard to provide feedback to individual physicians on the scale that you need. Some of what McKesson Health Solutions is working on is focused in this direction. We use analytics in an effort to find where the prescriber variations are, and what adjustments or interventions are needed to improve care and control costs. And it works: I have found that physicians do not like to be outliers for reasons they cannot explain. If you show

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see DR. MOELLER, page 6

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Volume 2 • Number 4 • Fall 2013

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Specialty Pharmacy Continuum • Fall 2013

POLICY

Ethical Hazards of High-Cost Drugs Need Study San Antonio—Bioethicist Norman Daniels, PhD, worries that the increased use of expensive specialty drugs may be coming at a high cost to society. He told attendees of the National Association of Specialty Pharmacy’s Strategic Business Exchange that the Affordable Care Act will likely increase equity and drug access overall but could still leave some patient access gaps. “We know there are industry efforts to address gaps based on financial need, but we don’t have any good studies on their impact as well as on potential access gaps left by these programs,” Dr. Daniels, a professor in the Department of Global Health and Population at Harvard School of Public Health, in Boston, told Specialty Pharmacy Continuum. A substantial body of research examining access gaps to the broader health care system has found that even when economic barriers are addressed, there is a racial disparity in access. The disparity “shows up, in every income level, over and above the effects of economic status,” Dr. Daniels noted. Copay-offset programs and foundation subsidies reach some, but Dr. Daniels said they probably leave some historically excluded minorities–including blacks and Hispanics–without effective treatments. “We’re likely to find very serious race disparities in access to costly specialty drugs,” Dr. Daniels said. “The problem again is that we don’t have good data.” The specialty pharmacy industry

AFFORDABLE CARE continued from page 1

education for patients, drug administration training, and medication adherence monitoring and intervention, Mr. Calabrese said, but they also will be expanded to include a broader complement of clinical care. “This means meeting quality metrics in the management of patients with key chronic conditions, many of whom will be treated with these specialty products,” he said. The additional services could include screening for comorbidities, conducting qualityof-life assessments, soliciting subjective patient-reported safety and effectiveness information, capturing key lab findings and documenting disease exacerbation and adverse events that may not require hospital or clinic care, he said. Atheer Kaddis, PharmD, the senior vice president of sales and business development at Diplomat Specialty Pharmacy, in Flint Mich., agreed that specialty pharmacies will have to offer more clinical services and measure more outcomes. However, with greater responsibility will come greater influence, he said. “The formation of ACOs [accountable care organizations] will

‘We’re likely to find very serious erio er ious io us race rac ace e disparities in access to costly tly tl y specialty drugs. The problem em is is that we don’t have good data.’ ata ta.’ .’’ —Norman Daniels, PhD hD faces an ethical imperative to investigate the question of drug access, Dr. Daniels said. Moreover, he said that the industry’s increasing use off data warehouses places it in a good position to undertake such an effort. “One very constructive project for specialty pharmacies would be to ask what a good registry to collect these data would look like and how open individual databases could be to researchers,” Dr. Daniels said. There is another ethical dilemma that the industry needs to confront, given the increasing use of high-cost specialty pharmaceuticals, Dr. Daniels noted. “There are clear budgetary impacts and opportunity costs associated with the

provide specialty pharmacies with the opportunity to partner with health systems, health plans [and] provider groups, and this can potentially position specialty pharmacies to be part of the solution in providing value-based care to patients,” said Dr. Kaddis, who was not involved in the NASP panel discussion. According to Dr. Kaddis, another factor that could draw specialty pharmacies into a more central role in the new health care environment will be the availability of biosimilars. “As biosimilars become available, specialty pharmacies will have the opportunity to participate in decision-making on formularies, benefit design and educational efforts with physicians, payors and patients,” Dr. Kaddis told Specialty Pharmacy Continuum.

Can Pharmacy Coverage Keep Up With Growing Demand? James Smeeding, RPh, MBA, the executive director of the NASP, told meeting attendees the specialty pharmacy industry is bound for growth. He added that the expanding pool of insured individuals will place an increased demand for a wide range of new specialty medications. “The rate-limiting variable will be wheth-

rising prices of specialty drugs,” he said. “It’s not clear what other services could be provided at a similar cost and are not being provided when an expensive specialty drug is administered.” He used the example of a high-cost oncology drug that might provide “a very modest life extension, on average, for a segment of patients.” He said that a decision to use this type of drug must be weighed against the cost and efficacy of other treatments that could

be provided in their place using those funds. “At the moment, there is no good mechanism to make a decision taking these opportunity costs into account,” Dr. Daniels said, reiterating that specialty cial ci a tyy pharmacy al ph stakeholders need to do so s me deep thinking about the e hi et h cs of o the industry. N L N. Lois Adams, B.Pharm, MBA, CR C RP Ph h, h the president and CEO of HHCS Health Group, in OrlanHH do o, Fla., seconded Dr. Daniels’ concerns and also added her own. Ms. Adams predicted tthat the increasing costs of special ci alty al tyy car aree ccould push specialty drugs further th eerr out of reach for some patients. Sh he su s ggested g that manufacturers shou uld co onsider the many specialty pharmacies phar arrma maci c e with expertise at treating a ci given disease when they are considering their distribution networks, rather than limiting them to the larger chains. She told Specialty Pharmacy Continuum that pharmacies with disease-specific expertise will often have “far better results” and “less costly waste” than some of the larger, more generalized operations. —David Wild Dr. Daniels and Ms. Adams reported no relevant ﬁnancial conﬂicts of interest.

‘Pharmacy benefit coverage under the ... health insurance exchanges are not well defined at this point and will evolve as the impact of the ACA is realized.’

—James Smeeding, RPh, MBA

er these individuals will have adequate pharmacy coverage” under the ACA, Mr. Smeeding said. “Pharmacy benefit coverage under the individual plans in the health insurance exchanges are not well defined at this point and will evolve as the impact of the ACA is realized.” Mr. Smeeding said anticipated approvals of a number of biosimilar drugs could mitigate some of the costs of specialty pharmacy care and narrow access gaps, but the extent of discount is another unknown. Yet another unknown is how the growing volume of specialty drugs will be distributed to the increasing number of insured individuals, he added. The restrictions on distribution are expected to be looser for biosimilars, and they could become available through a broader range of outlets, but there is a “yin-and-yang to this,” he said. “Since many of the anticipated bio-

similars are used as supportive care, if a patient’s primary drug is restricted for distribution only through certain specialty pharmacies, then the accompanying biosimilar used along with that product could also be limited to distribution from the same pharmacy channels,” Mr. Smeeding explained. As the myriad of possibilities in what Mr. Smeeding referred to as “the grand experiment” of affordable care take shape in the coming months and years, specialty pharmacy experts will be watching carefully. “As the ACA plays forward,” he concluded, “we’ll start getting good examples of the impact of the ACA and the positive benefits of the new health care environment.” —David Wild Mr. Calabrese, Dr. Kaddis and Mr. Smeeding reported no relevant ﬁnancial conﬂicts of interest.

Specialty Pharmacy Continuum • Fall 2013

POLICY

Surveying the SP Reimbursement Landscape Las Vegas—Specialty pharmacy reimbursement benchmarks and physician contracts vary widely across the country, even within payors, according to John Aforismo, BScPharm, RPh, FASCP, the chief executive officer of the Connecticut-based pharmaceutical consulting firm RJ Health Systems International LLC, which contracts with more than 170 payors across the country. “You’ll find physician contracts that are based on ASP [average sales price] plus, AWP [average wholesale price] plus, AWP minus, WAC [wholesale acquisition cost] plus, WAC minus and a hybrid, depending on the drug being utilized,” Mr. Alforismo said at the 2013 Armada Specialty Pharmacy Summit. But “the majority of payors had a reimbursement policy hovering somewhere near ASP plus 15%.” The majority of commercial contracts remain tied to AWP, he noted, but the WAC model has gained some traction because it is more stable—something that pleases providers and payors alike. Pharmacies dispensing to Medicaid patients, on the other hand, are now reimbursed based on yet another, relatively new formula—the average actual acquisition cost (AAC). “This reflects the final drug price paid by the pharmacy after subtracting discounts,” Mr. Aforismo said. “If this eventually becomes an accepted point of reference without much pushback, payors will take a leap of faith and go forward using this benchmark. Just as with ASP plus 6%, it was first introduced within Medicare, but commercial payors waited until they saw little pushback and then slowly integrated it into their models.” And then there’s the National Average Drug Acquisition Cost, a system developed by the Centers for Medicare & Medicaid Services in response to First Databank’s ceasing publication of AWP. “Is a new national benchmark needed?” asked Mr. Aforismo. “I truly don’t believe it is. If I hear one more person say AWP ‘Ain’t What’s Paid’—yes, it isn’t. Neither is the sticker price on a car. But it’s a reference point accepted since the 1970s. I honestly haven’t seen contracts deviating that much from

DR. MOELLER continued from page 4

them how they are diverging from other practitioners, some with better outcomes, they respond almost immediately. Q: How does current McKesson software address this concept of variation, and does it have application in the specialty pharmacy arena?

A: Much of my role at McKesson has been focused on claims auditing. So we are looking primarily at deviations from payor policy and from coding guidance.

Reimbursement by Segmenta Brand-name retail drugs: AWP minus 14% to 16% plus dispensing fee. AWP technically is no more, because its source, First Databank, ceased publishing that formula in its drug price data two years ago after challenges to the formula’s validity. (AWP was sometimes criticized as “Ain’t What’s Paid.”) But it survives nonetheless: “You can take the WAC and multiply by 1.2, and there’s your AWP,” said Mr. Aforismo.

Generic drugs: MAC plus dispensing fee. But generic drugs can have more than one MAC price, further complicating the picture. Each pharmacy benefit manager (PBM) chooses generics to add to their MAC lists and establishes pricing criteria for those drugs, using their own methodology. And most PBMs offer an AWP discount alternative for generics purchased from their own mail-order pharmacy to incentivize use.

Table. Reimbursement Formulas AAC

average actual acquisition cost

ASP

average sales price

AWP

average wholesale price

MAC

maximum allowable cost

NADAC

national average drug acquisition cost

WAC

wholesale acquisition cost

Specialty pharmacy drugs: An AWP discount that can vary substantially by drug, ranging from AWP minus 2% to AWP minus 35%. Home infusion is most commonly calculated using an AWP- or WAC-based formula. a

Based on 170 payors contracted with RJ Health Systems International LLC.

‘With specialty medications, you really need to take a look at what the treatment is to figure out the best cost equation.’ —Michael White, PharmD AWP.” What is really needed, he suggested, is for someone to coin an entirely new term for AWP—such as “PPP” (product purchase price). As more entries have come into specif-

ic therapeutic class areas, Mr. Aforismo said, payors are taking the opportunity to develop formularies in these classes. He said that of the health plans he works with, 63% have formularies for certain

On the specialty pharmaceutical portion of our business, our focus has been related to the HCPCS [Healthcare Common Procedure Coding System] J codes for specialty drugs, which can be very confusing. And that is because sometimes there are multiple codes based on the amount of drug that is prescribed and dispensed with a given product. So part of the content we put into our most recently released auditing logic was a ceiling on the number of units allowed for particular drugs. This helps avoid billing errors that result when a facility submits a code for 1,000 units of a drug

rather than one 1,000-mg dose, which can result in paying for 1,000 times too much drug. Without a ceiling on that unit field for that particular J code, those errors are going to get through automated claims processing. If you are processing a million claims a day, as many of our customers do, there is no way to look at the accuracy of those claims without automation. So without the type of deviation checks that our software can bring to the adjudication process, those errors might go undetected and would quickly add up. We’re also applying analytics and audit-

“specialty classes,” which may include at least some, if not necessarily all, of the following: biologic response modifiers, drugs to treat chemotherapy-induced nausea and vomiting, colony-stimulating agents, erythropoiesis-stimulating agents, growth hormones, hemophilia treatments, IV immune globulin products and multiple sclerosis treatments.

ACOs, Medical Homes in Play With the rise of accountable care organizations and medical homes, it should not be surprising that pricing models that are tied directly to the treatment guidelines for certain diseases also are being developed. “They’re based on episodes of care,” Mr. Aforismo said. In essence, a blanket monthly reimbursement—based on AWP, WAC or another formula—may be given based on treatment guidelines for a particular condition, including both primary therapies and ancillary medications. Payors now also are looking at reimbursement models that focus on frameworks such as average cost per treatment-day, average cost per duration of treatment and average annual cost per member per year, said Michael White, PharmD, the director of clinical pharmacy for Blue Cross and Blue Shield of Tennessee, who also spoke at the Armada Summit. This potentially means a more customized approach to reimbursement modeling. “Let’s use hepatitis C as an example,” Dr. White said. “The most important thing to consider with this disease is what is the cost per cure. For another condition, with other drugs, the equation might be different. With specialty medications, you really need to take a look at what the treatment is to figure out the best cost equation. Generally, cost per member per year is a robust way to look at it, but it will take a long time for the claims to accumulate so we can do that study.” —Gina Shaw

ing software to the utilization of oncology drugs (many of which are managed through specialty channels), because these agents can cost hundreds of thousands of dollars for a full course of treatment. We have software tools that can look for the approved diagnostic categories for these drugs, to ensure a very close match, and I am anticipating that we are going to see a lot better coding performance and reimbursement as health plans start to use this more extensively. —Interview conducted and condensed by David Bronstein

Specialty Pharmacy Continuum • Fall 2013

POLICY

Drug-benefit strategies a mixed bag for SPs

Employer Survey Reveals Cost-Cutting Toolls Specialty drug therapy for complex, chronic illnesses is the fastest-growing cost segment of employer-provided pharmacy plans, according to the results of a national survey by Towers Watson and the National Business Group on Health. As a result, employers are continuing to take a hard look at specialty drug utilization. “Continuing to pay for specialty drugs at an inflated rate of 30% to 40% year after year is not sustainable for most employers,” Nadina Rosier, PharmD, the North America pharmacy practice leader for Towers Watson, told Specialty Pharmacy Continuum. And there’s no fall-off in sight: Seven of the top 10 drugs that employers cover will be specialty drugs within the next two to three years, representing 40% to 50% of their total drug spend, she noted. (Other estimates say that eight of the top 10 drugs will go specialty in that timeframe.) Thus, it’s not surprising that employers are working hard to develop costcontrol strategies that can at least mitigate some of the financial bite of specialty drugs. To gain more insight into those strategies, Towers Watson and its survey partner polled employers with at least 1,000 workers and asked them for feedback on 10 financial and clinical management activities they’re exploring or currently using. The top activity on the list was “quantity or dose limits based on clinical evidence,” cited by 71% of respondents. Mark Zitter, the CEO of Zitter Health Insights, a health care research firm that was not involved in the Towers Watson survey, said that most specialty pharmacies would not object to this strategy because “no one wants to bump up against or exceed those maximum allowable limits.” However, other activities cited by the survey respondents may place some specialty pharmacy providers at risk. Mr. Zitter cited, as an example, the “carve-out of specialty drugs through a single vendor,” which ranked sixth on the list of cost-management activities and was mentioned by 37% of respondents. “If you’re not that preferred vendor or even one of a select few vendors, then you simply don’t have access to that drug—you’re on the outside looking in,” he said. Exclusion from those contracts can quickly add up in lost revenue opportunity, he noted. This trend of relying on a very limited network of specialty pharmacy providers is not going away anytime soon, Mr. Zitter added. “With more orphan drugs coming out, and more medica-

tions being approved that have significant safety issues, manufacturers often prefer to distribute through only a few specialty pharmacies,” he said.

second on the list of activities employers use to manage the drug benefit. This approach often means that self-administered drugs are encouraged as a first-line option in order to avoid infusion fees, Mr. Zitter said. And that’s a mixed bag for specialty pharmacy. On one hand, he explained, because specialty phar-

A Step in the Wrong Direction? Another potentially problematic strategy is “step therapy,” which was cited by 64% of the respondents and ranked

•

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Specialty Pharmacy Continuum • Fall 2013

POLICY

2012 Spend Stayed Low, but Pressure Building A brief, idyllic period of contracting growth in overall pharmacy spending is about to come to an unpleasant halt. That’s one of the main insights to be gleaned from 2012 trend reports released in June by two major pharmacy benefit managers, Prime Therapeutics and Catamaran Corporation. Both paint a very similar picture of the trajectory of pharmacy spending over the past year. Both pharmacy benefit managers (PBMs) saw low growth for overall pharmacy spending, with Catamaran’s growth at 2.6% and Prime’s, at 2.1%. Of course, the mass move to generics is the primary factor that has continued to push traditional pharmacy spending down, but there’s not a lot more to be squeezed from that fruit, said Peter Wickersham, Prime’s senior vice president of cost of care. “We expect that there will be in excess of an 85% generic dispensing rate for traditional pharmacy by the end of this year, and, ultimately, the traditional market will reach a steady state close to 90% generic and 10% brand. We are reaching the

peak of generic opportunity.” That means that the unabated—and increasing upward—pressure of specialty spending will have no release valve on the traditional pharmacy side, and, as a result, overall pharmacy spending is estimated to increase more dramatically, starting in 2015. Prime and Catamaran both boast aggressive specialty pharmacy management programs, and it is these programs, they said, that have kept their 2012 specialty spending growth relatively low: Prime’s at 19.1%, and Catamaran’s at 21%. By comparison, in a study of 60 employer clients presented at a March meeting of the National Business Group on Health,

‘For any specialty pharmacy to be successful ... [it] has to master pharmacy benefit claims communication ... [between] the payor and patient.’ —Albert Thigpen

Express Scripts reported that employers classified as “unmanaged” saw their specialty spend increase by 27.8% for 2012. When “unmanaged,” “somewhat managed” and “tightly managed” employers were taken together, Express Scripts reported an overall 18.4% increase in specialty spend. Increased use accounted for a modest chunk of Prime’s and Catamaran’s increases—4.8% and 6.7%, respectively. But the primary driver of the spending growth was a whopping 12% rate of price inflation. “That’s just not sustainable,” Mr. Wickersham said—particularly given that the current pipeline of drug development is 40% specialty. Some savings can be gleaned through aggressive management, according to both Prime and Catamaran’s trend reports. Catamaran reported that its “highly managed” clients saw a 1% spend increase compared with the company’s overall 2.6% increase. Prime, meanwhile, reported that its “active management” efforts saved the Blues plans that men own n the company $36 per member per yearr—or $720 million, when multiplied by 2 20 million members. Integration of medical benefit managgement with management of the pharmacy side is critical to keeping p th he specialty spend under control, said Alb bert Thigpen, Catamaran’s senior vice pressident of pharmacy operations and indu ustry relations. “If you think about the evolution of the pipeline and where cerrtain specialty pharmacy products arre going to evolve from, more and more are going to be covered under m thee medical benefit. For any specialty pharrmacy to be successful, including BriovaR Rx [Catamaran’s specialty pharmacy offerring, accredited by URAC earlier this yearr], the specialty pharmacy has to master p pharmacy benefit claims communication n, and, more importantly, bring the [med dical and pharmacy sides] together to b build a respectable picture of what’s goin ng on [with] the payor and [with] the patieent with respect to specialty care.”

Mr. Wickersham agreed. “You can’t just address half the problem …. all PBMs will be doing this. At Prime, we don’t have two separate approaches to managing utilization for a condition like rheumatoid arthritis, for example, which has an infused drug, Remicade, going through the medical benefit and others in the pharmacy benefit.” And even previously “hands-off” categories, such as oncology, will become much more closely watched with the growth of the oral oncolytics market, Mr. Wickersham and Mr. Thigpen agreed. But just as generics have applied the pressure needed to bring overall pharmacy spending down, many people are looking to biosimilars to alleviate the runaway growth of specialty spending. At this year’s Armada Specialty Pharmacy Summit, in Las Vegas, experts agreed that biosimilars must overcome a number of hurdles before they can become a real factor in the U.S. pharmacy market. In a session on the topic, Apogenics Healthcare founder David Galardi, PharmD, predicted a “bumpy road,” and said that he did not expect the first biosimilar to be approved for another two to four years. But Mr. Thigpen predicts a flurry of action sooner. “Catamaran suspects that there will be much activity around the entry of biosimilars in 2015, both from the regulatory side and the pharmaceutical industry side,” he said. “Many issues are currently being debated as to which proposed pathway governing substitutability and interchangeability against the innovator brands will prevail. We do know that the current biosimilar market in Europe has been successful and it is a relative proxy to what can happen in the U.S. market.” Ultimately, a very small number of drugs (and patients) will drive the majority of spend growth, Mr. Wickersham predicted. “I think we’ll get into a model where you have a couple of therapeutic classes on the specialty side that are really high-cost, that we will be managing very closely; 99% of the utilization is going to be relatively much lower cost than 1% of the market that will be driving the overall trend.” —Gina Shaw

Specialty Pharmacy Continuum TWEETS! Follow us @SpecPharmNews And send your Twitter handle to David Bronstein at davidb@mcmahonmed.com so we can follow you.

Specialty Pharmacy Continuum • Fall 2013

POLICY

WHITE BAGGING continued from page 1

executive director of the National Association of Specialty Pharmacy (NASP). Mr. Smeeding and Ernie Anderson Jr., MS, RPh, a Brockton, Mass.–based health care consultant, discussed the challenges posed by the white bagging of specialty medications during the recent Oncology Pharmacy Education Network meeting, held before the Association of Community Cancer Centers National Oncology Conference. Both agreed that one of the biggest challenges posed by white bagging is the complex nature of the specialty pharmaceuticals involved. The drugs, they noted, often require special handling, temperature-control monitoring and product-specific support services. As for the financial hit that health systems take as a result of white-bagging, Mr. Anderson cited a number of contributing factors. He noted, for example that when drugs come through specialty pharmacy, hospitals and clinics need to manage the logistics of acting as a courier service, often without compensation. Maintaining a patient-specific supply requires working with numerous specialty pharmacies, sometimes for the same drug, as well as dealing with varying requirements from different insurance companies. Moreover, health-system pharmacies bear the cost of providing ancillary supplies (e.g., needles, syringes) and managing unused drugs because a patient has died or a dose has changed. “When I was at Steward Health Care and Lahey Clinic, we had a whole section on the shelf that contained specialty medications,” said Mr. Anderson, who worked at both Massachusetts facilities. “It’s a lot of work to keep track of those drugs, and you don’t get any reimbursement for doing all the logistics.” (Mr. Anderson pointed out that white

bagging should not be confused with brown bagging, which occurs when a patient brings medicines to a clinic that they acquired through a specialty pharmacy or a store. Most hospitals don’t allow brown bagging, so it’s not a major financial or operation concern.)

Operational Hassles In addition to causing financial hardships for hospitals and clinics, white bagging can have a negative effect on continuity of patient care and patient safety if it becomes unclear who is taking responsibility for caring for the patient. Other challenges include biomedical verification of devices for medication administration; verification of drug integrity/pedigree; and ensuring that Risk Evaluation and Mitigation Strategies requirements are met. The issue of drug pedigree and liability can be particularly vexing for hospitals, Mr. Anderson noted. “Who is assuring the integrity of the specialty pharmacy and who is legally responsible if something is wrong with the drug?” he asked. “Institutions don’t get reimbursed for mixing the whitebagged specialty pharmacy drugs, but they assume all of the liability for it.” Mr. Anderson cited yet another concern: if a health-system stops buying drugs because of white bagging, under some wholesale distribution contracts, it may end up having to pay increased prices for other drugs.

Hospitals and Clinics Respond Some health-systems are responding to this trend by pushing back during the prior authorization process, when requested to use a specialty pharmacy, and have not allowed white bagging under any circumstances. Other pharmacies have told insurers that they want to be paid for managing white bagging, but

COST-CUTTING continued from page 7

macies work more often with self-administered drugs, steps that require such drugs to be used first will, in most cases, increase the use of specialty pharmacies. “However, if a step protocol requires one specific selfadministered therapy to be used first, and it is anything but the preferred drug, that could slow the process of specialty pharmacy delivering drugs to patients,” Mr. Zitter said. That strategy, he noted, “also defers [a specialty pharmacy’s] cash flow and adds extra cost to their operations—even if it does save money for the payor.” Towers Watson’s Dr. Rosier said that employers are not immune to concerns over delays in patient care, “and want to ensure there are limited barriers to access.” However, “with an excise tax looming for 2018, employers also want to aggressively manage the [pharmacy] benefit in more thoughtful ways.” Prior authorizations ran a close third in activities cited by employers, according to the survey. The costmanagement strategy, mentioned by 63% of respon-

few have been successful. Mr. Anderson emphasized that clinicians must bill zero dollars for the product along with an administration fee to collect a fee for administering specialty medications. For IV drugs, clinicians should mark down a start and stop time to be accurately reimbursed. If commercial insurance companies are using average sales price (ASP)-based reimbursement, pharmacies should request a fee of +25% to 30% over ASP to include pharmacy overhead, Mr. Anderson said. That number is supported by a 2005 Medicare Payment Advisory Commission study that revealed the actual costs of administering and preparing drugs. If a pharmacy ends up after negotiations with +15% or 20%, that is still a whole lot better than +6%, the current rate of payment set for hospitals. A few years ago, Blue Cross and Blue Shield of Massachusetts required that 30 self-injectable drugs come through specialty pharmacy. At the time, Mr. Anderson was system vice president at Steward. “Rather than say ‘we will not accept white bagging,’ what we said was, ‘if we are going to do white bagging, here are some of the criteria that we are looking for to make sure that we ensure the integrity of the product,’ ” he said. Alternatively, a hospital can take the plunge and become a specialty pharmacy provider. In Massachusetts, six hospitals have gained acces to specialty pharmacy contracts, and more are anticipated to do the same, Mr. Anderson noted. Elsewhere, hospitals and health systems throughout the country, including Cleveland Clinic, the University of Illinois at Chicago and Duke University have formed their own specialty pharmacies, either individually or as part of recently launched networks (see story, page 1). There is a checklist of several capabilities that hospitals have to master

dents, is a long-standing staple of most drug benefit plans, Mr. Zitter said, adding that he’s not surprised at its high ranking. “In some categories, payors perceive that most drugs are fairly similar from a safety and efficacy standpoint, so lots of them use this tactic to drive utilization to lower-cost therapies,” he said. “But it’s amplified even more now, because diseases being addressed are more serious and there aren’t inexpensive generic equivalents on the small-molecule side.” Formulary exclusions, tied for fifth place in the survey, “aren’t a hot button very often because pharmacists probably deal with many products within a category, and could suggest substitutes,” Mr. Zitter said. Nevertheless, Dr. Rosier was struck by the number of employers interested in employing this tactic: “We’ve seen a dramatic shift in the past year, likely spurred by marketplace events such as Express Scripts’ exclusion of Walgreens.” Limiting first-time prescriptions for oncology drugs to only partial fills was the least-cited cost-saving activity by health plans in the survey, at 17%. That low ranking represents a missed opportunity, Mr. Zit-

before establishing a specialty pharmacy, the speakers noted. They must, for example, have authorization by a third party and the ability to bill and adjudicate claims; maintain an inventory of specialty products; establish a variety of policies and procedures; and have a call center 24/7, 365 days per year. Becoming a specialty pharmacy also involves creating a delivery service with a tracking system, quality assurance, compliance and accreditation, provision of patient education materials, and meeting the standards from the FDA, National Comprehensive Cancer Network and compendia listing. If a hospital doesn’t want to become a specialty pharmacy, it should consider the partnership option, Mr. Smeeding suggested. “Partnering can offer some established care protocols, data management and infrastructure, payor contracting, pharma contracting and central distribution options.” Whether hospitals and clinics decide to get in the game or try to get paid for white bagging, they have to do something. Specialty pharmacy drugs represent a small percentage of prescriptions, perhaps 2%, but they can account for greater than 30% of expenditures, Mr. Smeeding pointed out. Moreover, “50% of the top 100 drugs and eight of the top 10 will be specialty pharmaceuticals by 2016.”

Help is at Hand Hospitals and clinics struggling with how to deal with specialty pharmacy will soon have help. The American Society of Health-System Pharmacists is expected to release guidelines on coordinating patient care with specialty pharmacy services in December 2013 or early 2014. —Kate O’Rourke Drs. Smeeding and Anderson have no relevant ﬁnancial disclosures.

ter stressed. A well-designed partial fill program can reduce waste and differentiate a specialty pharmacy with payors, and “can help you add value to what threatens to become a commodity business.” Most payors are aware of the waste issue and how costly it can be, Mr. Zitter noted. “If you ask them how much of first-time oncology prescriptions are wasted, they’ll say 20% to 30%,” he said. “This relates first to excessive care at end of life, and also to nonadherence of a therapy that’s delivered but not fully used. If a pharmacy ships $5,000 worth of product, and the person doesn’t take it because he or she doesn’t like the side effects or dies, it’s waste. “It’s smarter for a specialty pharmacy to ship 10 days’ worth to see how it works, and ship the rest after calling the patient to confirm it’s OK to do so,” he added. “Shipping smaller quantities of cancer drugs twice a month instead of larger quantities once a month can also help.” For the full report on the Towers Watson survey, visit bit.ly/GzKAx1. —Al Heller

Specialty Pharmacy Continuum • Fall 2013

TECHNOLOGY

Medication Adherence in the Palm of Your Hand “The smartphone will see you now.” That, declared noted cardiologist and technology guru Eric Topol, MD, might well be the motto for the next generation of health care. In a wide-ranging keynote address at the Armada Specialty Pharmacy Summit, in Las Vegas, Dr. Topol, the chief of innovative medicine at Scripps Research Institute, in La Jolla, Calif., described an array of new remote monitoring and diagnostic options that are either already available or coming soon to a smartphone, tablet or computer near you, including apps that measure and track lung function, blood sugar, heart rate and blood pressure, and can even perform an electrocardiogram. Such personalized digital intervention (PDI) tools enable health care providers to tailor care more specifically for individual patients, noted Al Babbington, CEO of PrescribeWellness, a company that provides cloud-based providerto-patient communications. Such PDI “technologies must be more effectively leveraged to provide patients the support necessary to improve outcomes,” Mr. Babbington said during the Centers for Disease Control and Prevention’s recent Conference on Health Communication, Marketing and Media. Remote monitoring via smartphone

and other technology tools is likely to transform the practice of pharmacy within the next few years, and holds particular promise for solving—or at least mitigating—a challenge that has long confounded pharmacists: patient nonadherence. One example: eMedonline, a “medication adherence telehealth platform” that already has secured multiple rounds of National Institutes of Health funding. It works on multiple devices—smartphones, BlackBerrys, and, for patients with no such devices, a basic Internet appliance from the company. This tool gives “the patient … a reminder on their phone or their device when it’s time to take a specific dose of medication,” said Kevin Clauson, PharmD, an associate professor of pharmacy practice at Nova Southeastern University, in Fort Lauderdale, Fla. “Then, they have to use the camera on their phone or a scanning app to scan the specific bottle or pill that they’re taking. The program then confirms that they’re getting the right drug, at the right dose, at the right time. time.”

In some cases, the patient then is prompted to answer a few questions about the medication via text, such as “How do you feel this drug is working for you?” and “What side effects have you noticed?” The data can be used to do predictive modeling, Dr. Clauson told Specialty Pharmacy Continuum. “For example, if the data shows that your patient is usually taking all of their doses correctly, but on Tuesday afternoons they often miss a dose, you can pinpoint what might be happening then. The patient might realize, ‘Oh, that’s when I take Ella to soccer, and there’s so much going on that I forget.’ So, you can develop nonpharmacologic interventions to help the pharmacologic piece.” AdhereTech’s patented “smart bottles” approach compliance from another direction. Somewhat akin to scales at the grocery store self-checkout lane that notice if you’ve pulled that two-ounce magazine back out of your bag, these vials measure the exact amount of pills or liquid in a bottle in real time and wirelessly send the information to a system that reminds patients to take their medication via automated phone calls or text messages. “If you don’t take the medication after tthat, the prompts become more

‘If you don’t take the th medication ... the prompts become beco more insistent. They’ll text, then they’ll t call, then maybe they’ll call ca your mom.’ —Kevin Clauson, PharmD —K insisteent. They’ll text, then they’ll call, then m maybe they’ll call your mom,” joked Dr. Clauson. “You can control how m much you want that to escalate.” Adh hereTech recently got funding throu ugh Pilot Health NYC, a project of the New York City Economic Developm ment Corporation and Health 2.0, forr a trial at Weill Cornell Medical Center, where it will be used tto assess patient adherence to an HIV drug regimen over a 12-week period and compare it with the usual standard of care. Maybe the most promising and the most controversial drug aadherence technology is Helius, tthe long-awaited ingestible bioseensor from Proteus Digital Health, which got the green light H fro om the FDA last year after four yeears of wrangling over exactly ho ow the agency would oversee it. (It was ultimately approved as a de

novo medical device because there is no comparable technology on the market.) An “ingestible event monitor” is embedded within a pill a patient takes; that monitor then communicates with a patch worn on the patient’s stomach. “The other devices are proxies— strong proxies, but still proxies,” said Dr. Clauson. “But with a biosensor, you know where and when the patient takes the drug; it also transmits basic physiologic data as well as drug disposition information. That’s not a proxy; that’s actual adherence.” Dr. Clauson noted that when the sensor was rolled out in the United Kingdom, it wasn’t piloted through clinics or hospitals. “They partnered with Lloyds, a pharmacy chain, to introduce Helius.” Some pharmacies are working to develop their own remote monitoring tools. Diplomat Specialty Pharmacy, the largest privately owned specialty pharmacy in the United States, is developing an interactive texting tool that uses decision-tree technology to allow automated two-way conversations based on the patient’s responses. Describing how the texting tool works, Gary Rice, RPh, Diplomat’s vice president of clinical services, said, “If you want to validate that a patient took their medication today, you can send them a text asking if they took it. If they did, then you’re done, and the system records that the patient has acknowledged taking their medication. If they say no, they’ll get another text message asking which of five reasons describes why they haven’t taken it.” If, for example, the patient selects “side effects,” the system will ask, “Which of the following side effects are you experiencing?” At some point, the patient can ask to be transferred to a live pharmacist for education on managing that particular side effect; if the side effects described are severe enough, they may be transferred directly to their physician’s office. Mr. Rice told Specialty Pharmacy Continuum that Diplomat plans to implement this program over the next year “to enhance [their] patient care management program.” The transition of the health care system from a fee-for-service to a “feefor-outcomes” model, the participatory medicine movement and quantum-leap advances in technology are converging to jump-start remote monitoring, said Dr. Clauson. “It’s not a wave of the future. It’s quickly becoming a wave of the present.” —Gina Shaw None of the sources reported any relevant ﬁnancial conﬂicts of interest.

Specialty Pharmacy Continuum • Fall 2013

TECHNOLOGY

Florida Pharmacists’ App Wins Microsoft Challenge

ealth eConnect, a prototype smartphone app created by research fellow Zaher Hajar, PharmD, and a team of colleagues at Nova Southeastern University’s College of Pharmacy’s Center for Consumer Health Informatics Research (CCHIR), has won an international contest seeking the most innovative apps to manage health. Sponsored by Microsoft, the contest, which called on innovators to design a next-generation health management app, awards a $10,000 first prize as well as what many smartphone app designers might regard as an even better bounty: inclusion as one of the Windows 8 “preferred partners” for 2013-2014, and a waiver of the standard $20,000 “golive” fee when the app is submitted to the Windows store. Dr. Hajar and his team, including CCHIR’s director, Kevin Clauson, PharmD, designed Health eConnect to leverage the individual health data that are stored on Microsoft’s HealthVault platform. The app uses a wireless interface to connect with devices such as

blood pressure cuffs, glucometers and activity trackers, and then gives patients a user-friendly, visually appealing assessment of their health status, along with reminders about what they need to do to actively manage their health. “The pharmacist is the most accessible health care provider nowadays, and we know what the patient needs in terms of engagement,” Dr. Hajar told Specialty Pharmacy Continuum. “We wanted to design an app that would

really help individuals with their dayto-day health management.” Because the Microsoft challenge was only one month long, Dr. Hajar and his team chose one piece of the app—the blood pressure section—to complete as a prototype. With the award secure, they now plan to design the medication section in a way that will sync with major pharmacy chains that are compatible with Microsoft HealthVault. “Then we can use this information to provide spe-

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Specialty Pharmacy Continuum • Fall 2013

CLINICAL

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Services in Deerfield, Ill. In a poster she presented at the Oncology Nursing Society’s 38th Annual Congress (abstract 363), Ms. Luszcz noted that the American Society of Parenteral and Enteral Nutrition recommends

BIVIGAM [Immune Globulin Intravenous (Human), 10% Liquid] Rx only Brief summary: Consult the full prescribing information for complete product information WARNING: ACUTE RENAL DYSFUNCTION AND ACUTE RENAL FAILURE Use of Immune Globulin Intravenous (IGIV) products, particularly those containing sucrose, has been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death1,2. Patients at risk of acute renal failure include those with any degree of pre-existing renal insufficiency, diabetes mellitus, advanced age (above 65 years of age), volume depletion, sepsis, paraproteinemia, or receiving known nephrotoxic drugs. Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. BIVIGAM does not contain sucrose. For patients at risk of renal dysfunction or failure, administer BIVIGAM at the minimum dose recommended and the minimum infusion rate practicable. Indication and Usage: BIVIGAM is an Immune Globulin Intravenous (Human), 10% Liquid, indicated for the treatment of primary humoral immunodeficiency (PI). Contraindications: BIVIGAM is contraindicated in patients who have had an anaphylactic or severe systemic reaction to the administration of human immune globulin. BIVIGAM is contraindicated in IgA deficiency patients with antibodies to IgA and a history of hypersensitivity. Warnings and Precautions: Thrombotic Events: Thrombotic events may occur following treatment with IGIV products. Patients at risk include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization, and/or known/suspected hyperviscosity. Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies. For patients judged to be at risk of developing thrombotic events, administer BIVIGAM at the minimum rate of infusion practicable. Hypersensitivity: Severe hypersensitivity reactions may occur with IGIV products, including BIVIGAM. In case of hypersensitivity, discontinue BIVIGAM infusion immediately and institute appropriate treatment. Medications such as epinephrine should be available for immediate treatment of acute hypersensitivity reactions. BIVIGAM contains trace amounts of IgA ( 200 micrograms per milliliter). Patients with known antibodies to IgA may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. BIVIGAM is contraindicated in IgA deficient patients with antibodies against IgA and a history of hypersensitivity reaction. Acute Renal Dysfunction and Acute Renal Failure: Acute renal dysfunction/failure, osmotic nephrosis, and death1,2 may occur upon use of human IGIV products. Ensure that patients are not volume depleted before administering BIVIGAM. Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure. Assess renal function, including measurement of blood urea nitrogen (BUN) and serum creatinine, before the initial infusion of BIVIGAM and at appropriate intervals thereafter. If renal function deteriorates, consider discontinuing BIVIGAM. In patients who are at risk of developing renal dysfunction, because of pre-existing renal insufficiency or predisposition to acute renal failure (such as diabetes mellitus, hypovolemia, overweight, use of concomitant nephrotoxic medicinal products or age of >65 years), administer BIVIGAM at the minimum infusion rate practicable. Hyperproteinemia, Increased Serum Viscosity, and Hyponatremia: Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IGIV therapy, including BIVIGAM. It is critical to clinically distinguish true hyponatremia from a pseudohyponatremia that is associated with or causally related to hyperproteinemia with concomitant decreased calculated serum osmolality or elevated osmolar gap, because treatment aimed at decreasing serum free water in patients with pseudohyponatremia may lead to volume depletion, a further increase in serum viscosity, and a possible predisposition to thrombotic events. Aseptic Meningitis Syndrome (AMS): AMS may occur infrequently with IGIV treatments including BIVIGAM. AMS usually begins within several hours to 2 days following IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae. AMS is characterized by the following signs and symptoms: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting. Cerebrospinal fluid (CSF) studies frequently reveal pleocytosis up to several thousand cells per cubic millimeter, predominantly from the granulocytic series, and elevated protein levels up to several hundred mg/dL, but negative culture results. Conduct a thorough neurological examination on patients exhibiting such signs and symptoms, including CSF studies, to rule out other causes of meningitis. AMS may occur more frequently in association with high doses (2 g/kg) and/or rapid infusion of IGIV. Hemolysis: IGIV products, including BIVIGAM, may contain blood group antibodies that can act as hemolysins and induce in vivo coating of red blood cells (RBCs) with immunoglobulin, causing a positive direct antiglobulin reaction and, rarely, hemolysis. Delayed hemolytic anemia can develop subsequent to IGIV therapy due to enhanced RBC sequestration,13 and acute hemolysis, consistent with intravascular hemolysis, has been reported. Monitor patients for clinical signs and symptoms of hemolysis. If these are present after BIVIGAM infusion, perform appropriate confirmatory laboratory testing. If transfusion is indicated for patients who develop hemolysis with clinically compromising anemia after receiving IGIV, perform adequate cross-matching to avoid exacerbating ongoing hemolysis. Transfusion-Related Acute Lung Injury (TRALI): Noncardiogenic pulmonary edema may occur in patients following IGIV treatment14including BIVIGAM. TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Symptoms typically appear within 1 to 6 hours following treatment. Monitor patients for pulmonary adverse reactions. If TRALI is suspected, perform appropriate tests for the presence of antineutrophil antibodies in both the product and the patient’s serum. TRALI may be managed using oxygen therapy with adequate ventilatory support. Transmissible Infectious Agents: Because BIVIGAM is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. No cases of transmission of viral diseases or CJD have been associated with the use of BIVIGAM. All infections suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Biotest

screening cancer patients for nutritional status frequently and intervening early if necessary (JPEN ( 2009;33:472-500). Nutritional support is more beneficial to patients when they are undernourished, with only minor weight loss, than when

Pharmaceuticals Corporation at 1-800-458-4244. Before prescribing BIVIGAM, the physician should discuss the risks and benefits of its use with the patient. Monitoring Laboratory Tests: Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk of developing acute renal failure. Assess renal function, including measurement of blood urea nitrogen (BUN) and serum creatinine, before the initial infusion of BIVIGAM and at appropriate intervals thereafter. Because of the potentially increased risk of thrombosis with IGIV treatment, consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies. If signs and/or symptoms of hemolysis are present after an infusion of BIVIGAM, perform appropriate laboratory testing for confirmation. If TRALI is suspected, perform appropriate tests for the presence of antineutrophil antibodies in both the product and patient’s serum. Interference with Laboratory Tests: After infusion of immunoglobulin, the transitory rise of the various passively transferred antibodies in the patient’s blood may yield positive serological testing results, with the potential for misleading interpretation. Passive transmission of antibodies to erythrocyte antigens (e.g., A, B, and D) may cause a positive direct or indirect antiglobulin (Coombs’) test. ADVERSE REACTIONS:Serious adverse reactions observed in clinical trial subjects receiving BIVIGAM were vomiting and dehydration in one subject. The most common adverse reactions to BIVIGAM (reported in 5% of clinical study subjects) were headache, fatigue, infusion site reaction, nausea, sinusitis, blood pressure increased, diarrhea, dizziness, and lethargy. Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials cannot be directly compared to rates in the clinical trials of another product and may not reflect the rates observed in clinical practice.In a multicenter, openlabel, non-randomized clinical trial, 63 subjects with PI, on regular IGIV replacement therapy, received doses of BIVIGAM ranging from 254 to 1029 mg/kg (median dose 462.8 mg/kg) every 3 weeks or 4 weeks for up to 12 months (mean 317.3 days; range 66 – 386 days). The use of pre-medication was discouraged; however, if subjects required pre-medication (antipyretic, antihistamine, or antiemetic agent) for recurrent reactions to immune globulins, they were allowed to continue those medications for this trial. Of the 746 infusions administered, 41 (65%) subjects received premedication prior to 415 (56%) infusions. Fifty-nine subjects (94%) had an adverse reaction at some time during the study. The proportion of subjects who had at least one adverse reaction was the same for both the 3- and 4-week cycles. The most common adverse reactions observed in this clinical trial were headache (32 subjects, 51%), sinusitis (24 subjects, 38%), fatigue (18 subjects, 29%), upper respiratory tract infection (16 subjects, 25%), diarrhea (13 subjects, 21%), cough (14 subjects, 22%), bronchitis (12 subjects, 19%), pyrexia (12 subjects, 19%), and nausea (9 subjects, 14%). Adverse reactions (ARs) are those occurring during or within 72 hours after the end of an infusion. In this study, the upper bound of the 1sided 95% confidence interval for the proportion of BIVIGAM infusions with one or more temporally associated adverse reactions was 31%. The total number of adverse reactions was 431 (a rate of 0.58 ARs per infusion). Seven subjects (11.1%) experienced 11 serious ARs. Two of these were related serious Table:Adverse Reactions (ARs) (within 72 hours after the end of a BIVIGAM infusion) in 5% of Subjects No. Subjects No. Infusions With ARs Reporting ARs ARs (% of Subjects) (% of Infusions) [n=63] [n=746] Headache 27 (43%) 115 (15.4%) Fatigue 15 (24%) 59 (7.9%) Infusion Site Reaction 5 (8%) 5 (0.7%) Nausea 5 (8%) 8 (1.1%) Sinusitis 5 (8%) 5 (0.7%) Blood Pressure Increased 4 (6%) 5 (0.7%) Diarrhea 4 (6%) 4 (0.5%) Dizziness 4 (6%) 4 (0.5%) Lethargy 4 (6%) 4 (0.5%) Back Pain 3 (5%) 3 (0.4%) Blood Pressure Diastolic 3 (5%) 5 (0.7%) Decreased a Fibromyalgia 3 (5%) 17 (2.3%) Migraine 3 (5%) 8 (1.1%) Myalgia 3 (5%) 4 (0.5%) Pharyngolaryngeal Pain 3 (5%) 3 (0.4%) a Symptoms occurring under pre-existing fibromyalgia ARs (vomiting and dehydration) that occurred in one subject. One subject withdrew from the study due to ARs related to BIVIGAM (lethargy, headache, tachycardia and pruritus). All 63 subjects enrolled in this study had a negative direct antiglobulin (Coombs’) test at baseline. During the study, no subjects showed clinical evidence of hemolytic anemia. No cases of transmission of viral diseases or CJD have been associated with the use of BIVIGAM. During the clinical trial no subjects tested positive for infection due to human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). There was a single positive finding for parvovirus (B19 virus) during the study. This subject came in contact with acute B19 virus from working at a school greeting children where a child was reported to have symptomatic Fifth's disease. There was no cluster (no other cases in other subjects) of B19 virus transmission with the IGIV batch concerned. DRUG INTERACTIONS Live Virus Vaccines: Immunoglobulin administration may transiently impair the efficacy of live attenuated virus vaccines such as measles, mumps, rubella, and varicella because the continued presence of high levels of passively acquired antibody may interfere with an active antibody response. The immunizing physician should be informed of recent therapy with BIVIGAM so that appropriate measures may be taken.

Table. Changes in Body Weight as Nutritional Intervention Triggers Significant Weight Loss, %

Severe Weight Loss, %

1-2

1 mo

3 mo

7.5

>7.5

6 mo

>10

Time

Source: Luszcz N, ONS abstract 363, adapted from Blackburn GL et al. J Parenter Enteral Nutr 1977;1:11-22. 1977;1:111 22.

‘A significant number of cancer patients have already experienced weight loss by the time they are diagnosed.’ —Noreen Luszcz, RD, MBA, CNSC they are severely malnourished, having experienced significant weight loss, she said (Clin Nutr 2009;28:445-454). “Every new patient admitted to Walgreens home infusion services by a nurse undergoes a complete nutrition evaluation, which includes a review of the patient’s diet, appetite, weight and a comprehensive gastrointestinal system review,” she told Specialty Pharmacy Continuum. If a patient is identified as being at risk for malnutrition, the nurse and a dietitian issue recommendations to the treating physician to improve the patient’s nutritional status. “The clinician may provide guidance to the patient as to how to increase calories and protein, as well as recommending use of oral supplements,” she said. “If the patient continues to deteriorate nutritionally, enteral [EN] or parenteral nutrition [PN] may be indicated.”

Screening Tools Available Nutritional assessment tools such as the Patient-Generated Subjective Global Assessment and the Malnutrition Screening Tool are widely available to clinicians, so it is not the absence of screening tools that accounts for untimely malnutrition screening and intervention. Furthermore, Ms. Luszcz said that clinicians who find these tools too cumbersome can simply use observed weight changes to decide on the necessity for a nutritional intervention and

Specialty Pharmacy Continuum • Fall 2013

CLINICAL

IVIG and Aseptic Meningitis

Jerry Siegel, PharmD, FASHP Clinical Associate Professor The Ohio State University College of Pharmacy Columbus, Ohio

’ve been involved with the development and management of intravenous immunoglobulin (IVIG) therapy for more than 30 years, and questions about the optimal use of IVIG are emailed to me on an almost daily basis. Many of those queries touch on safety issues, such as the review and monitoring of adverse reactions. I want to make this column as relevant as possible, so please send me your questions on IVIG therapy via email to Jerry.siegel.rx@gmail.com (cc: spceditor@mcmahonmed.com), and I will do my best to answer them. Each quarter, we’ll choose the most compelling question or patient case and use it as the basis for my column.

: Can IVIG cause aseptic meningitis and, if so, what can be done about it? A : Intravenous immunoglobulin (IVIG) is used as replacement therapy for patients with primary immune deficiencies and immunotherapy for patients diagnosed with idiopathic thrombocytopenic purpura (ITP) and numerous neuropathies. Patients often require large doses of IVIG to be given over several hours. A rare, but serious, side effect that can happen with IVIG therapy is aseptic meningitis. This adverse reaction was first reported in 1988.1 The term aseptic meningitis refers to a presentation of clinical and laboratory evidence for meningeal inflammation and negative bacterial cultures.2 The cerebrospinal fluid (CSF) white blood cell count ranges from 200 to 6,670 × 109/L (pleocytosis), and in most patients there is mildly to moderately elevated CSF protein with a normal CSF glucose concentration.3 Aseptic meningitis has been reported following administration of agents such as anti-inflammatory drugs (ibuprofen, naproxen), sulfonamides, allopurinol, methotrexate, and IVIG.2 The exact mechanism is not well known, but possible mechanisms include hypersensitivity reaction, reaction to stabilizing products, cytokines, cerebrovascular sensitivity, and direct meningeal irritation. In a majority of patients with IVIGassociated aseptic meningitis, signs and symptoms occurred within 48 hours of the IVIG infusion, while some cases presented as late as 10 days after the infusion.2 Most of the reported cases had ITP as the primary disease or received high-dose IVIG therapy. In a Japanese study, investigators found that

how aggressive it should be (Table).

Barriers to Best Practice One way to improve detection and intervention could be to educate clinicians on the benefits of adequate nutrition, including a lower mortality risk ((J Parenter Enteral Nutr 2007;31:451-455), according to Randy Fasnacht, RPh, the director of pharmacy at Advanced Infu-

Table. Recommended Steps for IVIG Rechallenge After Aseptic Meningitis Determine the osmolar load of the IVIG product used prior to the aseptic meningitis (see Siegel J. Pharmacy Practice News Special Edition 2011; http:// www.pharmacypracticenews.com/download/IVIG_safety_ppnse11_WM.pdf). Determine if lowering concentration or diluent will bring the osmotic load of IVIG to 300 mOsm/L. If changing the concentration is not possible, select a product that has an iso-osmolar concentration. Use a 3-stage escalation to titrate the infusion rate, but infuse at 50% of the maximum infusion rate of the previous infusion. Pre-medicate the patient with acetaminophen.

next question, then, is should the IVIG product be changed when rechallenging the patient? Because the exact mechanism of action for this adverse event is not understood, some general principles should be considered. To prevent an increase in meningeal pressure, it would be prudent to use a product and concentration of IVIG that is nearly isotonic. Some IVIG products can be very hyperosmolar when concentrated (1,250 mOsm/L), and when given at a rapid rate, they may decrease tolerability. This does not completely explain why aseptic meningitis usually does not appear for about 48 hours to up to 10 days after the infusion.

Instruct the patient to monitor for migraine and meningeal symptoms and to immediately report any problems.

References

If aseptic meningitis occurs on rechallenge, consider other treatment options.

1. Kato E, Shindo S, Eto Y, et al. Administration of immune globulin associated with aseptic meningitis. JAMA. 1988;259(22):3269-3271.

Subcutaneous administration of immunoglobulin may be considered to improve tolerance.8

over a 10-year period between 2000 and 2009, 384 patients with Kawasaki disease, developed aseptic meningitis after IVIG.4 Patients with a history of migraine are more likely to develop this adverse effect. Different immunoglobulin preparations had no significance on the incidence of aseptic meningitis.5 Risk factors for developing aseptic meningitis in this patient population include history of migraine headaches and high-dose IVIG therapy (2 g/kg per cycle). The symptoms of druginduced aseptic meningitis are selflimiting, with the majority of patients recovering within 5 days after the onset of symptoms. No specific therapy has been shown to decrease the duration of symptoms, although some patients have been treated with systemic corticosteroids.6 It has been advised that systemic therapy may not be indicated

and that supportive measures (fluid, electrolyte, and pain management) along with close observation may be the best approach.1 No deaths have been reported from aseptic meningitis associated with IVIG. Symptoms can recur with reinfusion.1,7 In one case, a patient who was diagnosed with ITP was treated with IVIG and 5 days later developed aseptic meningitis. Is it possible to give IVIG again since the patient has already experienced one of the rare side effects of IVIG therapy? Most of the patients who are being treated with IVIG are refractory and/ or high-risk patients, and since aseptic meningitis has not been shown to be fatal and the symptoms always resolve within a week of onset, it may be possible and necessary to rechallenge the patient with IVIG therapy (Table).8 The

sion Services in Akron, Ohio. “There are still those physicians who believe that if you feed the patient, you feed the tumor,” said Mr. Fasnacht, who was not involved in the abstract. Mr. Fasnach added that even those clinicians who know about the risks for malnutrition and use screening tools face administrative barriers to timely intervention. “Insurance companies and

Medicare and Medicaid are the thorn in everybody’s side,” he said. “You need to make sure you have reams and reams of documentation showing EN or PN are justified if you want to go ahead with it.” The need to overcome these educational and administrative barriers, as well as any others that prevent timely screening and nutritional intervention, is imperative, noted Mr. Fasnacht. “The

2. Kaarthigeyan K, Burli VV. Aseptic meningitis following intravenous immunoglobulin therapy of common variable immunodeficiency. J Pediatr Neurosci. 2011;6(2):160-161. 3. Al-Ghamdi H, Mustafa MM, Al-Fawaz I, Al-Dowaish A. Acute aseptic meningitis associated with administration of immunoglobulin in children: a case report and review of the literature. Ann Saudi Med. 1999;19(4):362-364. 4. Kemmosotu Y, Nakayama T, Matsuura H, Saji T. Clinical characteristics of aseptic meningitis induced by intravenous immunoglobulin in patients with Kawasaki disease. Pediatr Rheumatol Online J. 2011;9:28. 5. Sekul EA, Cupler EJ, Dalakas MC. Aseptic meningitis associated with high-dose intravenous immunoglobulin therapy: frequency and risk factors. Ann Intern Med. 1994;121(4):259-262. 6. Rao SP, Teitlebaum J, Miller ST. Intravenous immune globulin and aseptic meningitis. Am J Dis Child. 1992;146(5):539-540. 7.

Jayabose S, Roseman B, Gupta A. Aseptic meningitis syndrome (AMS) after IV gammaglobulin therapy (I.V. Gg) for ITP. Am J Pediatr Hematol Oncol. 1990;12:117.

8. Nelson MR, Carregal VA, Deguzman RD, Engler RJM. Aseptic meningitis due to intravenous immunoglobulin therapy that resolved with subcutaneous administration. Pediatr Asthma Allergy Immunol. 2000;14(4):323-327.

fact is we need to think about ensuring adequate nutrition from day one.” —David Wild Ms. Luszcz and Mr. Fasnacht reported no relevant ﬁnancial conﬂicts of interest. Mr. Fasnacht requested that his colleague, Talon Schroyer, a 2014 PharmD candidate, be cited as a contributor to the research that informed Mr. Fasnacht’s comments.

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Specialty Pharmacy Continuum • Fall 2013

Medi-Dose/EPS

CORPORATE SPOTLIGHT

ften, the most effective means of communication between health care professionals is through labeling. In order to meet this vital need for both pharmacy and nursing, Medi-Dose/EPS has specifically designed labels for every need from solids to liquids, syringes to ampules, IV lines and bags to insulin and suppositories. Plus, with our MILT 3.0 software, you can design your labels any way you want. In addition to being able to use graphics, special fonts, tall man lettering, shapes—even logos and symbols—to better identify your medications, MILT 3.0 has been designed to easily create bar codes with the information your bar code–enabled point-of-care and bar-code medication administration systems require. Popular 1-D and 2-D bar code formats can be created with NDC numbers, expiration dates, lot numbers and special codes. Here are some additional labeling systems we offer, with details on how they can help your facility improve medication handling and safety:

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Medi-Dose (Solid) and TampAlerT® (Liquid) Oral Unit-Dose Packaging Medi-Cup® PLUS packaging for extended beyond-use dating MILT® by Medi-Dose unit-dose and bar-coding software LiquiDose® labeling, IV additive and filtration products Nultraviolet® ultraviolet light inhibitant bags Steri-Dropper sterile ophthalmic dropper bottles High Alert and IV Line Tracing Labels Resealable bags, bottles and other pharmacy supplies and disposables

Specialty Pharmacy Continuum • Fall 2013

CLINICAL

Literature Scan

Latest Hepatology Studies: Impact on Practice Keeping up with the scientific literature is a difficult task, especially given the wide range of disease states managed by specialty pharmacy. So each issue, clinical experts will focus on one therapeutic area and comment on recently published studies, with this issue’s spotlight on hepatology.

Jacqueline O’Leary, MD, MPH Medical Director Inpatient Liver and Transplant Unit Baylor University Medical Center Dallas, Texas

nce-daily simeprevir (TMC435) with peginterferon and ribavirin in treatment-naive genotype 1 hepatitis C: The randomized PILLAR study. (Fried MW et al. Hepatology y 2013 Aug 2. [Epub ahead of print])

This international, multicenter, double-blind Phase IIb study examined the safety and efficacy of combination treatment with simeprevir, an oral hepatitis C virus (HCV) NS3/4A protease inhibitor, pegylated interferon (PEG-IFN) alfa-2a and ribavirin (RBV) in patients with chronic HCV genotype 1 infection.

logic response (RVR) after four weeks of treatment compared with 5.2% of placebo recipients. Additionally, between 75% and 86% of simeprevir recipients had a sustained virologic response (SVR) at week 24 of simeprevir treatment compared with 65% of placebo recipients ((P<0.05 for all vs. placebo, except SVR at week 24 for simeprevir 75 mg). A subanalysis that included only patients with HCV RNA levels less than 25 IU/mL after 24 weeks of simeprevir treatment revealed that 85% to 95.6% of these patients achieved SVR at week 24. Also, between 71% and 85% of simeprevir recipients achieved SVR at week 72 compared with 65% of placebo recipients. Viral breakthrough occurred in 6.4% to 7.8% of 12-week simeprevir recipients and 2.5% to 2.7% of 24-week simeprevir recipients compared with 5.2% of placebo recipients. Viral relapse occurred in 11.1% and 19.4% of 12- and

‘Although at launch, simeprevir will need to be combined with PEG-IFN and RBV, we anticipate utilization of this direct-acting antiviral agent (DAA) in combination with other DAAs in multidrug, IFN-free cocktails in the future.’ —Jacqueline O’Leary, MD, MPH Researchers randomly assigned 77 patients to receive PEG-IFN 180 mcg per week and RBV 1,000 to 1,200 mg per day in combination with placebo for 24 weeks, followed by an additional 24 weeks of treatment with PEG-IFN and RBV. Another 153 patients were randomly assigned to receive simeprevir 75 mg per day in combination with PEG-IFN and RBV for 12 or 24 weeks, followed by 24 weeks of treatment with PEG-IFN and RBV. A third group of 156 patients followed the same treatment regimen but with simeprevir 150 mg per day. Between 38% and 49% of patients had HCV genotype 1a infection, and most had the interleukin-28 B (IL28B) CT T genotype. The researchers reported that 68% to 76% of patients in the simeprevir treatment groups achieved a rapid viro-

24-week simeprevir 75 mg recipients, respectively, and in 8.7% and 8% of 12- and 24-week simeprevir 150 mg recipients, respectively; approximately 18% of placebo recipients experienced viral relapse. Serious adverse events (AEs) occurred in 3.8% to 11.5% of simeprevir recipients compared with 13% of placebo patients. There was no significant difference between groups in the rates of treatment discontinuation.

Dr. O’Leary: We are nearing the launch of a new protease inhibitor for HCV. Simeprevir is dosed once daily, does not worsen the anemia associated with PEG-IFN and RBV, and has minimal drug–drug interactions. Although at launch, simeprevir will need to be combined with PEG-IFN

and RBV, we anticipate utilization of this direct-acting antiviral agent (DAA) in combination with other DAAs in mult i d r u g, I F N -f re e cocktails in the future. For example, interim results from cohort 2 of the COSMOS study demonstrated that 12 weeks of treatment with simeprevir and sofosbuvir in patients with hard-to-cure HCV (prior null responders and treatment-naive patients with HCV genotype 1 and advanced liver fibrosis or cirrhosis) led to SVR rates at week 4 of 96% and 100% for treatment given with or without RBV, respectively.

ofosbuvir for previously untreated chronic hepatitis C infection.

(Lawitz E et al. N Engl J Med 2013;368:1878-1887)

Lawitz et al reported findings from two Phase III trials of sofosbuvir: NEUTRINO and FISSION. NEUTRINO included 327 treatmentnaive patients with chronic HCV infection: 292 patients with HCV genotype 1, 28 patients with HCV genotype 4 and seven patients with HCV genotype 5/6. All patients received sofosbuvir, an HCV NS5B polymerase inhibitor, 400 mg per day, in combination with RBV 1,000 to 1,200 mg per day and PEGIFN 180 mcg weekly, for 12 weeks. Seventeen percent of patients had compensated cirrhosis and 29% had IL28B CC genotype. At baseline, all patients had a platelet count of greater than 90,000/mcL; none had neutropenia, and the mean HCV RNA viral load was 6.4 log10 IU/mL. At week 12, 90% of patients achieved SVR, which is higher than the 60% rate demonstrated in historical controls, the researchers reported. All patients who did not achieve SVR at week 12 experienced viral relapse; no patients had HCV NS5B S282T resistance following relapse. Among patients with cirrhosis, 80% achieved SVR at week 12. Additionally, 92% of patients without cirrhosis, 96% patients with HCV genotype 4 and 100% of patients with HCV genotype 5/6 achieved SVR at week 12. The FISSION trial included 499 treatment-naive patients with HCV

genotype 2 or 3 infection. Patients were randomized to receive 12 weeks of treatment with sofosbuvir and RBV or 24 weeks of treatment with PEG-IFN alfa-2a and RBV, in an open-label fashion. In the sofosbuvir treatment group, dosing of sofosbuvir and RBV was the same as in the NEUTRINO study; in the control group, patients received RBV 800 mg per day, in two divided doses. Approximately 20% of patients in both groups had cirrhosis. Findings showed 67% of patients in both groups achieved SVR at week 12. One patient who received sofosbuvir and 18 patients in the control group had virologic breakthrough. Additionally, 29% of sofosbuvir recipients and 20% of PEGIFN/RBV recipients experienced virologic relapse after treatment. Subgroup analyses revealed that 97% of patients with HCV genotype 2 and 56% of those with HCV genotype 3 who received sofosbuvir achieved SVR at week 12 compared with 78% and 63% of genotype 2 and 3 patients, respectively, in the control group. Among patients with cirrhosis at baseline, 47% and 38% achieved SVR at week 12 in the sofosbuvir and PEG-IFN/RBV groups, respectively. In the FISSION trial, 1% of sofosbuvir recipients discontinued treatment due to an AE, 3% experienced a serious AE and 86% experienced any AE; corresponding rates in the PEG-IFN/RBV group were 11%, 1% and 96%, respectively. Common sofosbuvir-related AEs reported by patients in both the FISSION and NEUTRINO studies included fatigue, headache, nausea and insomnia. In the FISSION trial, 9% and 14% of sofosbuvir and PEG-IFN/RBV recipients, respectively, experienced a reduction in hemoglobin concentration. No patients who received sofosbuvir experienced decreased lymphocyte, neutrophil, platelet or white cell counts compared with 11%, 14%, 7% and 5%, respectively, of PEG-IFN/RBV recipients.

Dr. O’Leary: We are on the verge of FDA approval of the first HCV NS5B polymerase inhibitor. Sofosbuvir, a once-daily, active site nucleotide inhibitor, must be combined with PEG-IFN and RBV for 12 weeks in treatment-naive patients with HCV genotype 1, and holds the promise of 90% SVR rates, dropping only to 82% in patients with compensated cirrhosis. Patients with HCV genotype 2, regardless of fibrosis status, will now have an outstanding IFN-free treatment option, promising SVR rates that approach 100%. ■

Specialty Pharmacy Continuum • Fall 2013

COMMENTARY

Specialty Pharmacy: Building On Your Value Proposition Michael J. Baldzicki Executive Vice President Armada Health Care Florham Park, New Jersey

ore and more specialty pharmacies are emerging, building on key areas such as geographic coverage, therapy management programs and information technology–supported medical claim expansion. However, to deliver quality value-added propositions to their clients, specialty pharmacy companies must consider new lines of services or improve their current services. The shift toward new and improved services is necessary in view of shrinking profit margins resulting in large part from two factors: payors challenging specialty pharmacy networks and manufacturers looking toward specialty pharmacies to improve total-cost-of-care management for their products. As manufacturers work to change strategies around patient services, many companies continue to struggle with implementation, particularly spe-

Armada’s Strategies For Optimizing Specialty Pharmacy Initiatives

rmada is reshaping its role in the specialty pharmacy market with effective commercialization and channel management solutions, coupled with comprehensive patient support services for specialty pharmacies, including the following: • Armada Specialty Pharmacy Network (ASPN). ASPN offers biotech and specialty pharmaceutical manufacturers a scalable, managed pharmacy network, a core component to any commercialization or brand-management strategy. ASPN includes both specialty and open-access pharmacies across the nation. For Manufacturers: Armada is ready to structure a custom network solution to meet the needs of any manufacturer on demand. A single contract and a single reporting platform—all seamlessly supported by the Armada Managed Network Solution. ASPN can provide the initial network composition along with ongoing administrative oversight. For Pharmacies: Pharmacies can participate in ASPN based upon their therapeutic expertise along with other manufacturer requirements. ASPN can also assist your pharmacy with extensive patient support services. Through participation in the network, your pharmacy will receive valuable patient HUB referrals. • ASPN Prescription Transfer Program • Hub solutions—intake services • Pre-and post-launch commercialization strategies • Prior authorization support • Clinical support capabilities—online therapy management • Group purchasing organization services • Data management and reporting • Logistics and order fulfillment • Payer network expertise

Special programs that improve patient compliance and ensure cost-containment techniques will increase manufacturer’s product market access. cialty pharmacies that are having difficulty keeping up. Some key areas that specialty pharmacies should consider when developing or improving service offerings include: Establishing key partnerships. Part-

nering and outsourcing with key companies can increase a specialty pharmacy’s portfolio while reducing development costs and spreading risk. Partnering with payors also could bring mutual benefits.

Creating patient-centric programs. Establishing a patient-centric strategy and programs that focus on outcomes distinguishes a specialty pharmacy and creates long-lasting value. Key components of a patient-centric model include patient safety and clinical pharmacy services. Implementing a strategy. This approach involves the selection of key

•

see VALUE PROPOSITION, page 25

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Bridging the gap between the hospital and alternate-site care Volume 2 • Number 2 • Spring 2013 • specialtypharmacycontinuum.com

In This Issue Operations & Mgmt

Price not the key to a successful payer– specialty pharmacy partnership.

‘The Wheel’ keeps clients’ drug spend in check.

NASP panel: There is strength in numbers from SP stakeholder collaboration.

Helping To Close the Gaps in Specialty Care

Goads & Games Can Bolster Med Adherence

Part 1: Holistic patient management

San Diego—The staggering $317 billion that medication nonadherence costs our health care system each year can be chipped away at if pharmacists encourage proper medication use, an expert told attendees of the Academy of Managed Care Pharmacy’s (AMCP) 25th Annual Meeting and Expo. “None of the medicines we develop, none of our efforts to make sure these medicines are accessible to patients, none of the guidelines we create, none of these matter if we don’t actually get the medicine into a patient’s body,” said

Disease State Spotlight

•

A stepwise guide to IVIG product selection and use.

Clinical

Payers, providers need to be ready for Actemra in wake of positive studies.

Policy

Kynamro for HoFH gets SP distribution; FDA keeping close eye on drug.

Corporate Spotlight Medi-Dose/EPS see page 21

see ADHERENCE, page 17

Programs Cut Specialty Spend Growth in Half

San Diego—Specialty pharmacists are well positioned to narrow the significant and persistent gaps in patient care, experts told attendees of the National Association of Specialty Pharmacy’s Inaugural Specialty Pharmacy Conference. According to Diane Sullivan, vice president of the Payer and Channel Group at Pfizer Specialty Care, and the moderator of a roundtable discussion on the topic, approximately 55% of all patients in this country are receiving inadequate care. “It’s been 10 years since this number was first reported and we have the same gaps in patient care today,” said Ms. Sullivan, referring to a study from 2003 showing that preventive, acute and chronic care fell below evidence-based guidelines in 45% of patients (N ( Engl J Med 2003;348:2635-2645) and a more recent study showing that there have been no significant improvements in patient care since (Express Scripts 2012 Drug Trend Report.) In light of the frequency of interactions between specialty pharmacists and patients as well as the contribution of specialty pharmacists to improving medication adherence rates, there is a significant opportunity to raise the bar for patient care, Ms. Sullivan suggested. “Seventy percent of our specialty products are distributed and managed by specialty pharmacists, and for three of our products, it’s 100%. So, we really rely on the expertise of specialty pharmacy,” she said. “We know that from an adherence perspective, a patient will actually have a better experience with specialty pharmacy than with retail, where adherence rates are 8% lower.”

mployers who use multiple cost management programs to control their spending on specialty drugs spend an average of 50% less on these medications annually than employers whose specialty spending is totally unmanaged, according to a recent study by Express Scripts. Specialty pharmacy is expected to account for one of every four dollars spent on prescription medications by next year, and utilization management programs often are depicted as a critical element in controlling the runaway growth rate of specialty spending. But the actual impact of utilization management on spending is still being determined.

see CARE GAPS, page 18

see SPENDING CUTS, page 8

•

The Book Page Remington: An Introduction to Pharmacy

•

Special Report

Loyd V. Allen (Editor)

Understanding Key Differences Between Biosimilars and Small Molecule Generics

See page 25.

See insert after page ??.

Specialty Pharmacy Continuum • Fall 2013

OPERATIONS AND MANAGEMENT

EDUCATIONAL REVIEW

Ensuring Temperature Integrity Of Specialty Drugs: The Last Mile Part 1 of a 2-Part Series WILLIAM BAILEY, RPH Chief Operating Officer Citizens Rx Edwardsville, Illinois

he journey a specialty medication takes to the patient is a long one. The

first mile of the journey is from the manufacturer to the supplier. The last mile of the journey is the final leg of delivery from the pharmacy to the patient, which represents a safety and financial opportunity for the specialty pharmacy industry.

Half of the more than 900 biotechnology or specialty therapies estimated to be in the pipeline will need to be maintained within a certain temperature range for the medication to work effectively.1 This review will describe the path these sensitive and expensive lifesaving medications take from production to the patient, identifying the safety checks and processes in place for safe excursion through the delivery process. Figure 1 demonstrates the sample path the asset takes from a manufacturer to a patient, delineating the risks at each point in the process, starting with “the first mile,” from the manufacturer to the wholesaler and ending with “the last mile,” from the specialty pharmacy to the patient. Additionally, newly collected data regarding the viewpoint of the patient will be presented.

Managing Temperature-Sensitive Medications From the Manufacturer Many of the specialty medications expected to come to the market over the next several years will be monitored by the manufacturer. Temperature-sensitive medications (TSMs) are becoming increasingly prevalent as new drugs are developed, particularly in the specialty and

biotechnology arenas. In the past, insulin was one of the most common drugs associated with temperature management. Today, there are numerous medications that require temperature control during shipping and storage to maintain product stability and effectiveness. Use of a visual indicator can alert the end user that something has gone wrong in transit. Manufacturers of these medications develop stability data that identify safe temperature ranges within which these medications can be shipped and stored. Manufacturers are held accountable throughout the distribution chain by various regulatory agencies to ensure that these medications arrive safely to the patient. Manufacturers use a combination of packing materials strategically positioned with indicators that travel with the shipments to wholesalers, physicians, and specialty pharmacies. They take painstaking efforts to provide the correct combination of the shipping container (box), the pack-out schematic (Figure 2), and additional quality management tools (ie, indicators). The goal is to guarantee that these work 100% of the time to protect their asset, the specialty medication. These companies have invested time

and millions of dollars to create an “asset” on which they will base their futures. They understand how the drug was created and how easily it can be destroyed or deemed ineffective.

Managing TSM From Wholesalers After the drug leaves the manufacturer, the wholesaler is the next stop in the process. Like the pharmaceutical industry, the wholesale industry is highly regulated, and it shares responsibility for the safe delivery of many TSMs to the pharmacy or physician’s office. Wholesalers are bound not only by the financial obligation of protecting the asset but also by regulatory requirements and safety concerns for which they will be held accountable. Both the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) have established regulatory requirements to ensure the safe delivery of immunizations, the costs of which are well below the average cost of a specialty medication and which are administered with less frequency.2 The CDC requires not only appropriate packaging, but also the addition of an indicator to guarantee the stability and safety of all immunizations

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Manufacturer

Wholesaler Main warehouse

First Mile

Wholesaler Secondary warehouse

Second Mile

Specialty Pharmacy

Last Mile

Patient

Figure 1. A sample path temperature-sensitive medications take from manufacturer to patient, delineating the risks at each point in the process.

shipped from wholesalers. The WHO requires the use of appropriately approved packaging in combination with indicators for all immunizations shipped worldwide. Wholesalers have answered the need for effective monitoring of vaccines, using a strategic combination of packaging and visual indicators. Thus, wholesalers are prepared to similarly monitor the biotech and specialty medications they handle.

Managing TSM to the Pharmacy Next, TSMs travel from the wholesaler or manufacturer to the pharmacy. Some TSMs are shipped from centralized warehouses that serve as staging areas. In most cases, TSMs coming directly from the manufacturers and the wholesaler include a combination of methods to protect the asset. The added value of a temperature indicator creates a layer of visibility. Having an indicator of changes in the ambient temperature during transit is a valuable tool and validates that everything worked correctly during the shipping process. Delays in shipping or other factors in many cases go unrecognized or unreported without this indicator. This “second mile” of the shipping integrity of TSMs is fairly well managed today. The combination of appropriate packaging, processes, and visual indicators effectively reduces the opportunity for loss of assets due to suspected, but not verified, temperature excursions and prevents safety issues with the patient related to compromised medication. However, in the future, increased attention to this area will be required. New products coming to market in the next several years will fall under additional scrutiny because they are increasingly expensive and

complex in their stability requirements. There are many new products that will have stringent temperature requirements and will not be usable by patients if these requirements are not adhered to during the shipping process. These TSMs now have moved from the manufacturer to the wholesaler or centralized distribution center, and on to the pharmacy or physician’s office. Without indicators, these recipients often use unscientific means of identifying suspected temperature misadventures—touching the medication or sensing that the inside of the package is “too warm.” These unscientific judgment calls are completely inaccurate in many cases. This typically leads to a call to the supply entity to resupply the drug, which can result in additional costs and expense to the supply entity associated with a reship, a loss of trust between the patient and the supply entity, and, most importantly, an interruption in the patient’s treatment regimen. If there is a visual indicator, those who receive the shipments containing TSMs at the pharmacy or physician’s office are immediately alerted about any temperature excursions these medications may have encountered. The simple use of an indicator easily could relieve concerns or confirm them without any of the subjective guesswork. Use of such indicators conveys the idea that all processes and safety measures are in place to properly store TSMs while they wait to be administered, dispensed, or shipped.

Breakdown in ‘Last Mile’ The last mile is the specialty pharmacy segment shipping the TSM to patients or physicians. We trust that providers (physicians and Text continues on page 20

Figure 2. Exploded view schematic of temperaturesensitive product packaging.

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OPERATIONS AND MANAGEMENT

Indicated that they want the company sending their medication to include a temperature indicator

Reported being concerned about the temperature of medication sen sent to o them in the ma mail being too warm o or too cold

Reported that they would be concerned if their insurer switched from a company that used a temperature indicator to one that does not

Indicated ndicated that the they believe a company that includes a temperature indicator with shipped medication shows concern for their safety

hormone deficiency, multiple sclerosis, neutropenia, psoriasis, psoriatic arthritis, respiratory syncytial virus, rheumatoid arthritis, as well as patients undergoing transplantation. The survey response rate of patients ranged from 14% to 18%. Figure 3 shows a sampling of the responses received from surveyed patients. The results indicate that there is a significant opportunity to use visual indicators as a patient tool that, if managed well, can reduce reshipments and phone calls due to perception.

Safety Factors

Figure 3. A sampling of responses from surveyed patients.

Text continued from page 19

pharmacies) have all the safety standards in place before shipping, administering, and dispensing, but this can be where the safety and efficacy of the TSM is at risk. There are many box or shipment container suppliers in the marketplace today. They provide an array of options, sometimes with supporting documentation based on their own test criteria, and sometimes without any documentation. It is highly recommended that specialty pharmacies independently test their containers or boxes to meet the standards supplied by pharmaceutical manufacturers. The testing process should include a scientific tracking tool such as a thermal test chamber. Specialty pharmacies may find in many cases the need to make adjustments in one of their shipping processes or materials. They must confirm they are doing all they can to protect the specialty medication and maximize successful patient outcomes each time they make a shipment. The key question every specialty pharmacy should be asking is “will the manufacturer allow us to manage their branded asset if we are unable to ensure the medication will arrive safely to the patient every time?” Specialty pharmacies that show safe delivery of medications to the patient will top the list of eligible suppliers.

Typical Arguments Against Indicators There has been much discussion about whether to use temperature indicators in shipping TSMs, particularly very expensive specialty medications, to patients. Those who argue against the use of indicators voice the following concerns: “It confuses the patient,” “It generates more phone calls,” “There is no need for indicators since I never have returns,” “Manufacturers

always replace my product loss,” and “My box vendor told me my box is guaranteed safe.” Working in the industry for many years, I have voiced all of these rationalizations myself until a few years ago. However, after speaking directly with several patients, I began to question my validation of the reasons not to use indicators. What I heard was alarming, so I decided to take a closer look.

What Do Patients Think? Nobody had taken the time to ask patients if they felt safe taking the specialty medication that was shipped to them. That was not appropriate, considering that, after all, they are the customers. I engaged several industry partners to conduct a confidential scientific survey targeted at patients who receive these medications. The goal was to help understand if there may be an opportunity to help improve the following: • Reduction of reships due to “perceived temperature excursions” (ie, when the patient felt a medication was too warm upon receipt). • Understand patient concerns regarding the shipment of their TSMs. • Find a way to reduce inbound phone calls from patients by giving them an easy “tool” to feel safe and comfortable taking this shipped medication. • Poll patients as to their desire to have more information. The survey started 15 months ago and ended in fall 2013. More than 5,000 packages per week have been shipped with indicators. The geography of the country was taken into account, with all regions represented. The pilot study included medications for patients with anemia, Crohn’s disease, hemophilia, hepatitis C, HIV, growth

Safety is another factor that cannot be overlooked. Usually shipments arrive on time with no concern, but there are situations that are invisible to you and the patients that may create stability or safety concerns relative to TSMs. Such safety concerns about using a medication that is no longer stable are real. Boards of pharmacy are beginning to take a closer look at the shipping of TSMs as a whole. Additionally, several states have added language stating that the safety of patients is the responsibility of the pharmacy that ships the TSM.

Cost Concerns Cost concerns are 2-fold. The cost of losing a specialty shipment that may average $1,900 or more is significant for any specialty pharmacy. The loss might be because the package truly was exposed to temperatures that would make the product unusable. The loss may be a result of the patient or caregiver “perceiving” the product is too warm. This results in the loss of a perfectly viable product and additional costs to reship the product. In my current role, it is not unusual to see requests from our customers to identify how we as a pharmacy benefit manager protect the integrity of specialty medications. Those who cannot demonstrate control of the environment during shipping could be eliminated from consideration. This concerns the specialty medication itself as well as the cost of more expensive therapies, medical costs, or other negative effects that result from damaged product or subtherapeutic dosing. Reshipments are expensive and in many cases avoidable with a combination of the correct packaging and an easy-to-use temperature indicator, costing an average of $0.90 to $1.25—not a bad investment to save on expensive reshipments.

Therapeutic Concerns When a product cannot be used because its integrity cannot be verified, a missed dose

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OPERATIONS AND MANAGEMENT

potentially may occur. Many times one missed dose might be critical and might lead to negative health consequences, including death. Additionally, the use of a drug that has lost potency or effectiveness during excursion or shipping is an invisible concern. The shipping process noted above does not lend itself to visibility of environmental concerns that could potentially affect the specialty medication. As with a missed dose, use of an ineffective dose might contribute to morbidity and mortality.

Choosing the Right Combination Of Packaging and Indicators Patients are not versed in the concept of an excursion rate, the amount of time allowed by the manufacturer and supported by stability data that a medication may remain at a certain temperature without permanent damage. Many times they will call the specialty pharmacy when they have a concern. The conversation might begin with, for example, “I think my medication is too warm.” Perception plays a key role here. The average person is not trained to ask the right questions and to look for telltale signs of damage to the specialty medication. The specialty pharmacy may communicate that the specialty medication is usable and is not damaged. That may end the concern or perceived risk of injecting damaged medication there, or it may not. The patient might not be convinced and might next phone their doctor or the manufacturer, who may advise them the specialty medication is good, or that they should call the specialty pharmacy and have a new medication shipped. The phone calls and reshipping the medication could have been avoided with the right combination of packaging and an indicator. If the indicator has been activated and the medication went above a specific range of time and temperature, then you and the patient know it is time to reship—no questions asked and no safety risk. However, one of the concerns from many specialty pharmacies is that the indicators generate more phone calls and returns. We avoid such pitfalls by making sure all the necessary precautions are in place. I am not maintaining that the simple addition of an indicator will stop all specialty medication reships overnight. However, a system of steps can minimize the need for reships. The system consists of several variables, including but not limited to: • Manufacturer excursion recommendations • First-line customer service representatives (pharmacists, customer service representatives, patient care coordinators) who have the correct information in hand

Figure 4. An example of a customer-friendly temperature indicator.

• Choice of the right “box” or “shipping container” • Use of the correct configuration of ice packs, cold packs, and packing materials • Independent scientific testing to confirm your vendor’s validation documentation • Well-written procedures to support the correct packing configuration • Selection of an indicator that is reliable and easy for the general layperson to read Most professionals reading this article have the above bullet points checked off at this point. If the box is not validated, then it is probably a good idea to have an organization independent of the manufacturer test the box. You may be surprised. Does this mean you are going to discard the $30,000 worth of boxes and containers you have stored in that offsite warehouse? Probably not. You might have to reconfigure your packing process, however.

Selecting an Indicator This indicator selection process will be detailed in part 2 of this series. We will provide a “101” version here. Step 1 in the indicator selection process is to remember that a good indicator will work well and will cause alarm only if the box or container fails. It is possible your box has been failing all this time, but you never received a call. Step 2 in the indicator selection process is pairing the correct indicator to the recommended excursion ranges by the manufacturer. Step 3 is to pick something that is already activated. Some temperature indicators require “activation” before they work. My experience has been that at 6 PM when shipping is rushing that last order to the airport, they might miss that step. The patient then calls, believing the medication is not usable. Using an indicator

of this type will minimize the potential human error. Step 4 is to pick an indicator that is simple to read. Figure 4 shows an example of a customerfriendly indicator. It is easy for a patient or caregiver to make an immediate determination of the safety and stability of their medication. Thus, it is crucial that the indicator is properly activated and the patient can easily read it. The right combination of packaging and indicator will reduce reshipments, phone calls with temperature concerns, calls to payors, and concerns about medication effectiveness.

Conclusion The process of protecting patients and assets related to temperature-sensitive specialty medications is crucial to good medical and financial outcomes. The products and methods used to manage this process successfully will continue to evolve to ensure a safe and effective shipping process. Patient safety can be improved and loss of assets reduced if time and investment is allocated to the proper tools and processes. Temperature indicators are one of those essential tools.

References 1.

Center for Healthcare Supply Chain Research. 2012 Specialty Pharmaceuticals: Facts, Figures and Trends. Arlington, VA: Center for Healthcare Supply Chain Research.

2. Centers for Disease Control and Prevention. Vaccine storage & handling toolkit. November 2012. http://www. cdc.gov/vaccines/recs/storage/toolkit/storage-handlingtoolkit.pdf. Accessed September 26, 2013.

Part 2 of this series will discuss proper matching of shipping containers and indicators.

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OPERATIONS AND MANAGEMENT

Let Me In: Specialty Pharmacy Network Design Las V Vegas—Pharmacy networks are designed to reach a balance between patieent access and manufacturer control, with manufacturers considering factors such as productt profile, patient population, as well as payor and regulatory issues when deciding who w will be in their distribution networks, according to William Roth, founding partner of thee health care consulting company Blue Fin Group. “Every script matters,” said Mr. Roth, describing how manufacturers build their limited-distribution networks, during a session at the 2013 Armada Summit. “Even time to therapy matters. Without calling out names, I have a large manufacturing client about to pull its product from specialty pharmacies because it takes six weeks to get to firsttime-to-fill. Manufacturers are intolerant of service-level deficiencies.” Pharmacy networks, Mr. Roth said, are designed to reach a balance between patient access and manufacturer control. If a manufacturer feels that just one specialty pharmacy can allow for necessary patient access, it will choose that single pharmacy, achieve control and cut others out. “Manufacturers are going to take con-

trol of the channels,” he said. “Every large manufacturer that has a selfadministered product has a hub. If the pharmacies don’t do well with these products, they’ll simply take them out of the pharmacy and sell directly to the physician or the patient.” In designing a network, many factors come into play. “Manufacturers have to think through their product profile, their patients, the prescribers, the site of care, route of administration, payor issues and regulatory issues,” Mr. Roth said. For example, if a product is “ultraorphan,” Mr. Roth noted, the manufacturer will be thinking about a narrow network right out of the gate. “With the launch of Gilenya, the first oral product in multiple sclerosis [MS], you might think oral equals retail,” he said. “But there

are 400,000 MS patientss in the U.S., and d the biggest MS p product has just 100,000 of those. Why put a productt in 55,000 po oints of retail if you u are going to service 5,00 00 patients?” That said, the size of the typical speciaalty pharmacy network is growing som mewhat, said pharmaceutical economiccs expert Adam Fein, PhD, the founder and a president of Pembroke Consulting, a management advisory and business research firm. “The number of pharmacies that have thee capa-

Retailers Need To Evolve To Get Involved R etailers who want to participate in specialty pharmacy networks need to make some changes, according to experts. During a presentation at the 2013 Armada Summit, William Roth, founding partner of the health care consulting firm Blue Fin Group, launched into a salvo of complaints from manufacturers directed at retail pharmacy—the reasons, he said, why many retail pharmacies are not being asked to participate in specialty pharmacy networks.

prescription. “On a chronic medication, that’s not so big a deal, but with a specialty drug, it’s huge. And another 25% of prescriptions are lost to poor adherence in retail. You let over half our prescriptions fall on the floor! If I’m launching a specialty product, do you think I’m going to put it to retail? Retailers, I offer you a challenge: Clean it up, you’re broken!” But many retailers actually don’t have anything to “clean up,” because they have yet to truly take the specialty plunge, Marvin Allen, RPh, MBA, an associate vice president for specialty pharmacy contracts at Innovatix, LLC, told Specialty Pharmacy Continuum. “National chains have entered specialty through acquisitions of and mergers with existing specialty

“Some of the mini-chains are opening specialtyfocused pharmacies,” he said. “They’re not trying to convert an average retail pharmacy to specialty but instead are taking their capabilities and connections and migrating those to designated locations that are specialty focused.” 2. Partner with larger specialty pharmacies that can handle the back end in clinical services—such as Diplomat’s handling of many specialty pharmacy services for companies like Target and Safeway. 3. Acquire specialty pharmacies outright, such as Kroger’s purchase of Axium. 4. Develop collaborative networks to contract with payors and manufacturers.

‘There absolutely is a place for retail within specialty, but the needs of specialty drugs mean that the products and the customer relationships need to be handled differently.’ —Adam Fein, PhD

“There’s a 15% loss of prescriptions because they just never make it from the doctor to the pharmacy. Another 8% are lost to a service-level deficiency. The patient walks up to the counter and they [hear], ‘come back tomorrow.’” Or, he added, the pharmacy has some of the medication but can’t fill the full

pharmacy providers, while most regional and nontraditional retail pharmacies (e.g., supermarkets, mass merchandisers) have done little if anything with specialty,” he said. “Even those national retail chain pharmacies that have established a footprint in specialty tend to have more of a traditional mail-order focus as opposed to the sophisticated special services needed to support specialty products.” Those retailers who do want to get involved in specialty “have to evolve their capabilities if they want to participate, and some of them are,” said Pembroke Consulting’s Adam Fein, PhD, a pharmaceutical economics expert. He pointed to four key strategies that retailers are using to get in on limited-network distribution channels for specialty drugs: 1. Build internal specialty pharmacy capabilities.

“There absolutely is a place for retail within specialty, but the needs of specialty drugs mean that the products and the customer relationships need to be handled differently,” Dr. Fein said. Mr. Allen suggested that Dr. Fein’s third model— what he called a “private-label program”—could be one of the most promising business models for retailers wishing to enter specialty. “A private-label program is a business agreement in which a retail pharmacy contracts with an established specialty pharmacy to handle all patient and prescription protocols and to dispense the product with co-branded labeling and/or collateral material branded with the name of the retail pharmacy,” he explained. “In addition, the specialty pharmacy partner can provide back-office specialty services (clinical,

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bilities to be in limited networks continues to grow. URAC has accredited or is in the process of accrediting 80 specialty pharmacies. Typically, there are anywhere from five to 20 pharmacies in a manufacturer’s network, and the networks for non-orphan drug indications are starting to get bigger. It’s not appropriate for most of these products to be in a network of 60,000 retail pharmacies, but I do think manufacturers are feeling some pressure to open up their networks.” (See sidebar on advice for retail pharmacies that are interested in getting into specialty distribution networks.) Another determining factor in network design, Mr. Roth said, is the competitive landscape among manufacturers. “If a competitor has an exclusive network, so can you. If the competitor is wide open, that may influence you.” Traceability also is becoming a big selling point in specialty pharmacy networks. Mr. Roth described one client who uses serial IDs on their product in a limited network of specialty pharmacies. “When the 100 network pharmacies adjudicate claims, they do it with a serial ID linked back to the manufacturer,” he said. “I can know that there’s

reimbursement, REMS [Risk Evaluation and Mitigation Strategy], data management, etc.) for the retail pharmacy on a fee-for-service basis.” Doing that, he said, can greatly reduce prescription leakage and patient loss. “Currently, most retail pharmacies refer patients who present prescriptions for specialty drugs to larger PBM [pharmacy benefit manager]owned pharmacies. Because most of [those] pharmacies also are equipped to provide mail-order services for nonspecialty medications, they typically encourage patients to transfer their nonspecialty drugs to the PBM-owned pharmacy—which means the retail pharmacy loses all of those scripts.” Other advantages for the retailer include a substantially smaller investment than building a specialty pharmacy from scratch or purchasing an existing business, and the ability to provide branded continuum of care services for patients who are in closed or limited distribution networks and are using specialty drugs. Retailers also can phase into the specialty market via this model, which allows for more of a learning curve, Mr. Allen said. “This model also provides retailers with a tremendous amount of flexibility,” he said, “including the ability to target those specialty disease states that have few, if any, drugs on limited or closed distribution to launch their specialty retail offering.” —G.S.

‘Every script matters. Even time to therapy matters.’ —William Roth no fraud or abuse, because you can’t reuse my package.” This level of personalization, on all fronts, is likely to become more and more characteristic of specialty pharmacy networks, he said. “I have another client where the CEO of the com-

pany knows every single patient who’s on their drug. He knows if they take it. He knows if they’re a week late getting their infusion. That’s the level of depth involved. Try that with any primary care product!” The competitive jockeying for position to participate in specialty pharmacy networks ultimately is good for patients, noted Dr. Fein. “Competition will only improve the services that specialty pharmacies are providing.”

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Specialty Pharmacy Continuum • Fall 2013

OPERATIONS AND MANAGEMENT

Hub Websites Engage Patients and Caregivers Specialty drug hub programs are increasingly serving as the key source of information on everything from co-pay offset programs to disease information. However, new data collected by Zitter Health Insights have shown that a well-designed hub also can increase use of a drug. “Hubs can help overcome the complex processes involved in accessing specialty drugs,” said Adina Safer, a senior vice president at ADVI in San Francisco, who has helped design drug hubs and who was not involved in the Zitter research. “We’ve got lots of fragmentation and poor communication between stakeholders, and the reimbursement and coverage processes are complicated.” Chris Wheeler, the director of copay strategies at Zitter Health Insights, whose offices are located in Milburn, N.J., and San Francisco, presented the Zitter data in a recent webinar, and cited data demonstrating the broad impact of a strong hub. “We know hubs are driving patient adherence to prescribed therapy, for example,” Mr. Wheeler said, noting that 84% of 101 rheumatologists surveyed by Zitter indicated that, in their experience, hub-based rheumatoid arthritis (RA) co-pay offset programs improved their patients’ adherence to therapy. According to Mr. Wheeler, standalone co-pay offset services such as hotlines are giving way to hubs that offer not only information on co-pay offsets, but a range of other resources. These include resources related to foundation assistance programs, information for providers on reimbursement and coding, patient education, and directories listing pharmacies where the medication can be purchased. “Our preliminary data [show] that disease and clinical support, physician outreach and access and coverage components, all have a high impact on physician utilization of hubs,” Mr. Wheeler told Specialty Pharmacy Continuum. “For example, more than half of rheumatologists and RA patients we surveyed indicated they used the RA hubs’ coverage services in addition to the co-pay benefit.”

Financial Assistance Still Key Ingredient Despite the importance of these ancillary services, Mr. Wheeler said the patient financial assistance component is still the most important element of a hub. In a survey of 25 RA patients conducted by Zitter, most respondents said their choice of a specific medication was “highly influenced” by the availability of a co-pay offset program. Another Zitter survey of 101 oncologists showed that 53% of oncologists prescribed an oncology drug “solely due to something

ADVI’s Ms. Safer said she believes that Genentech’s Access Solutions is a good example of a “very well thought out, robust program for the user.” One of the website’s strengths is that it simplifies and outlines the reimbursement process, she said. Indeed, according to Zitter Health data, 95% of the oncologists they surveyed felt their staff and patients had to endure a “moderate to high level of hassles” in using co-pay offset programs.

‘More than half of rheumatologists and RA patients we surveyed indicated they used the RA hubs’ coverage services in addition to the co-pay benefit.’ —Chris Wheeler Genentech’s Access Solutions website hub includes resources for 14 of the company’s specialty medications, including Tarceva (shown above).

related to the co-pay offset program.” “Across the board, research suggests that co-pay assistance drives utilization, in and outside of hubs,” Mr. Wheeler said.

of that company’s specialty drugs— illustrates this well, he said. For example, a Zitter survey of 101 oncologists found that half of the physicians prescribing Erivedge, Tarceva, Xeloda and

‘A growing number of manufacturers are seeing hubs as an extension of their brand, and many have created in-house teams to design and manage them, giving them more direct control of their branding.’ —Adina Safer The financial assistance piece is also directly relevant to specialty pharmacies, according to a smaller Zitter survey of 11 specialty pharmacists; most said physicians were more likely to refer patients to a specialty pharmacy that they believed would help patients find financial assistance and remain medication-adherent.

Multi-Brand Hubs Have Higher Utilization Rates Interestingly, some hub design elements might be as powerful as the information they transmit, Zitter data suggest. “In hubs that incorporate multiple brands, use of one of the drugs included on the website can help drive utilization of other drugs on the same hub,” Mr. Wheeler told webinar attendees. Genentech’s Access Solutions—a website that includes resources for 14

Zelboraf said they frequently used the hub’s oncology co-pay offset programs. In contrast, only 7% and 4% of physicians prescribing Pfizer’s Xalkori and Inlyta—two drugs with two separate hubs—used those medications’ hubbased co-pay offset programs. Similarly, rates of foundation assistance program utilization were highest for drugs featured on Genentech’s multidrug Access Solutions hub (Figure). Mr. Wheeler said data like these point to the impact of the multi-drug design but that “it is only one element of an effective hub.” He noted that patient assistance programs on other manufacturers’ multi-brand hubs are utilized at low rates. “An insight like this shows how much variability there is in hub design and how important it is to understand what makes for a strong hub,” he said.

“A multi-brand hub such as Genentech’s is also easier to navigate than having to work with multiple hubs for individual brands,” added Ms. Safer.

Hub Design Landscape Changing As someone who has helped launch several hubs, Ms. Safer has seen the hub designer landscape change over the past few years: The number of pharmacy benefit manager–owned specialty pharmacies providing hub design and management services has dwindled, and most of those that continue to offer these services are larger players like Express Scripts and AmeriSource Bergen, or they are stand-alone private firms. “One reason for this is that a growing number of manufacturers are seeing hubs as an extension of their brand, and many have created in-house teams to design and manage them, giving them more direct control of their branding,” she explained. Mr. Wheeler said Zitter will keep monitoring the hub design industry as these websites proliferate and engage a growing number of specialty drug patients and physicians. He said, “Manufacturers will continue to leverage hubs (both internal or external) to facilitate the complex reimbursement process for all those who are involved—the patient, their caregivers, the physician and the office staff.” —David Wild Mr. Wheeler and Ms. Safer did not report any relevant ﬁnancial conﬂicts of interest.

Specialty Pharmacy Continuum • Fall 2013

OPERATIONS AND MANAGEMENT

HOSPITALS continued from page 1

president of supply chain at the Chicago, Ill.-based organization. Coupled with a toolkit to further promote such compliance, UHC members now have the puzzle pieces in place to become a major player in the specialty pharmacy arena, according to Mr. Groenewold. “We anticipate that 80% of out members should be able to participate,” he told Specialty Pharmacy Continuum.

Help With Data Aggregation One of the traditional knocks against individual hospitals or health systems providing specialty pharmacy services is the channel’s inability to provide robust clinical data aggregation—a major requirement of many specialty drugcontracts. UHC is addressing that perceived shortcoming by running a central data repository that tracks patient outcomes, Mr. Groenewold noted. As for the toolkit that is being developed for members, it will help facilities manage Risk Evaluation and Mitigation Strategies (REMS) compliance, cold-chain integrity, quick time to first dose, regimen adherence, around-the-clock clinical support, patient counseling and monitoring of patient experience. Typically, each hospital’s main pharmacy will administer the program. To placate smaller manufacturers with niche drugs, UHC has a single distribution point in mind. From this hub, UHC would redistribute specialty medications to participating hospitals. Doug Smith, PharmD, the senior director of UHC’s capital resource program and supply chain services, said that “smaller manufacturers told us if they were to include UHC in their distribution, they’d want one UHC-level contract that would encompass all participating members.” Members drove this initiative, Dr. Smith added, noting that Andy Pulvermacher, RPh, the specialty services supervisor at the University of Wisconsin Hospital and Clinics, in Madison, and Kevin Colgan, RPh, MA, FASHP, the corporate director of pharmacy at Rush University Medical Center, in Chicago, played key roles on the 27-member task force. “They went to [the] Armada [Specialty Pharmacy Summit meeting] with

VALUE PROPOSITION continued from page 17

programs that assist and support the strategy. The specialty pharmacy programs that improve patient compliance and ensure cost-containment techniques will increase a manufacturer’s product market access. There are several service paths for

me last spring. We spoke with 13 specialty drug manufacturers there about our idea, and asked, ‘is this on point.’ Our program reflects their input. It also reflects the views of other manufacturers engaged by UHC members who have mature specialty programs of their own.”

Continuity of Care

will want to assure that utilization of specialty pharmaceuticals is appropriate, and will want to manage that risk themselves using their own specialty pharmacy programs,” he said. “Our focus is on our ability to manage patients and our financial liability going forward as ACO participants.”

Other Networks & Initiatives

is considerable, given the exploding market for specialty pharmaceuticals. By 2016, eight of 10 new drugs will be moving through specialty channels, and the script volume for these medications is projected to grow by more than 20% annually. Thus, hospitals urgently want to be within specialty drug networks. “The gold rush is on,” Mr. Cohen said. That should not be surprising, he noted, “with new patients in the system, new drugs in the pipeline, mounting care needs and the evolving ACO model.” Indeed, Mr. Cohen sees specialty “becoming the norm for all pharmacies.”

Mr. Colgan stressed that a main impetus for the UHC program is “to reduce fragmentation of care in the current model” and to cut confusion for patients and their caregivers when they try to access specialty pharmaceuticals. “Academic medical centers can improve patients’ overall care experience by providing benefits investigation, prior authorization, patient monitoring, education and prescription services, all from the same location.” Currently, UHC sees many instances where outpatients want a UHC member facility to dispense a specialty drug and care for them, but the patients must first call an 800 number to have an authorized distributor directly ship them the drug, which they bring in with them for treatment. This “white-bagging” process leaves obvious gaps in clinical care, potentially disrupts the assurance of cold-chain integrity, and makes it far more difficult to bolster and document regimen adherence (related story, page 1). UHC could deliver continuity of care with greater access to specialty drugs, and that would improve patient safety and compliance, Mr. Groenewold noted. JoAnn Stubbings, BSPharm, the assistant director of specialty pharmacy services at University of Illinois at Chicago, a UHC member, agreed that continuity of care is crucial. “It certainly was an important driver in our decision several years ago to seek access to specialty pharmacy contracts,” she said. Outsourcing those services, she added, was not a viable option “because it doesn’t really make as much sense in light of health reform and ACOs [accountable care organizations], where the health system assumes risk for transitions in care. It’s tough to do that when you’re locked out of limited distribution networks for specialty drugs and then can’t control for high-risk patients.” Taking a more direct role in the provision of specialty pharmacy care is the major focus of the UHC initiative, Mr. Pulvermacher noted. “Our members

Nevertheless, it is obvious to multiple sources that financial and market forces are indeed at play in this move by hospitals to grab a piece of the specialty pharmacy pie. In spring 2012, Fairview Health System, in Minnesota, and Henry Ford Health System, in Michigan, spearheaded a national network of hospital pharmacies named ExceleraRx, LLC that aims to unite at least 20 large, integrated health systems in an effort to win specialty share. At the time, they told Specialty Pharmacy Continuum that their hospitals lost 30% to 40% of their most vulnerable and complex patients to other specialty pharmacies due to limited distribution of drugs. Gary Cohen, BSPharm, RPh, CSP, the CEO of the National Association of Specialty Pharmacy, said that it is logical for hospitals and health systems to make this move. Nationwide, “they are moving in the direction of being able to provide specialty pharmacy services on an outpatient basis,” he said. “With the development of the ACO model [where money flows through health systems and hospitals], initiatives like ExceleraRx and UHC will proliferate.” Mr. Cohen cited several reasons why hospitals are well positioned to become players in the specialty pharmacy arena. “Hospitals already have the ability to transfer specialty patients from inpatient to outpatient services,” he said, adding that those patient acquisition skills are “the key part of the triangle that includes access to specialty drugs and contracts for reimbursement.” The financial benefit of this strategy also should not be overlooked. “Hospitals now realize they don’t have to abdicate revenue to outside [specialty] pharmacy services, especially when they already have the skill sets and medical records to serve complex patients,” Mr. Cohen said. The potential growth of that revenue

But what about established pharmacy providers’ take on this trend? Although not specifically addressing UHC’s announced strategy, Phil Hagerman, RPh, CEO of Diplomat Specialty Pharmacy, pointed out that his company already has a track record of welcoming hospitals into the fold. “Over the past several years, Diplomat has created leading products to support some of the nation’s top retailers and hospitals in developing their specialty pharmacy strategy,” he said. “We are excited and proud to be supporting many of the nation’s top hospital systems in that build-out.” Several other large specialty pharmacy providers declined to comment on the UHC initiative, either specifically or in broad strokes. But Ms. Stubbings said she has heard all of the claimed reasons why health systems are ill-suited to enter the specialty pharmacy market— and doesn’t buy them. “It’s been suggested by key players in the specialty pharmacy arena that health systems ‘can’t do REMS or meet the other criteria,’ and I would ask them for specific reasons or proof why not,” she said. “It is a claim that is completely unsubstantiated. Health systems are in a better position than all of those other entities to implement and execute REMS, especially because we have access to the [patient’s] electronic medical record. “At our institution, I know we have several partners in specialty pharmacy who are very happy with our performance, including the most important partner—the patient.” —Al Heller

specialty pharmacies to consider, each providing a value proposition. Nonetheless, the specialty pharmacy segment must be built around improving patient outcomes. Establishing specialty pharmacy contracts and agreements with payors will help drive additional value to both the managed care organization and the patient by providing additional patient education, improved

adherence and other cost-management techniques. Additionally, specialty pharmacies can add value with their expertise and local relationships, and can gain preferred provider status with key regional payors. In conclusion, specialty pharmacies need to consider key collaborations, such as developing custom payor programs and services to share therapeutic exper-

tise, demonstrate improved patient care, build effective outcomes management and develop total-cost-of-care programs. These changes require new distribution and management strategies between payors, manufacturers, specialty pharmacies and pharmacy benefit managers. Specialty pharmacies that fail to prepare for these key market shifts and challenges could lose ground. ■

SP Industry Reactions

Specialty Pharmacy Continuum • Fall 2013

FDA WATCH

FDA Approves Two New Options For Treatment of Psoriatic Arthritis

anssen Biotech announced that the FDA has expanded the use of Stelara (ustekinumab) to include the treatment of active psoriatic arthritis (PsA) in adults in addition to its previously approved indication for plaque psoriasis. Within a week of that announcement, UCB reported that its agent Cimzia (certolizumab pegol), previously approved for rheumatoid arthritis and Crohn’s disease, also received approval for the treatment of adult patients with PsA. The new indication for ustekinumab, a fully human anti–IL-12/23p40 monoclonal antibody, is supported by findings from two pivotal Phase III multicenter, randomized, double-blind, placebo-controlled trials in patients with active PsA. PSUMMIT I and PSUMMIT II evaluated the efficacy and safety of subcutaneously administered ustekinumab 45 or 90 mg at weeks 0 and 4, and then every 12 weeks. The trials included 927 patients diagnosed with active PsA who had at least five tender and five swollen joints and C-reactive protein levels of at least 0.3 mg/dL in spite of previous treatment with conventional therapy. PSUMMIT II also included 180 patients with previous exposure to one to five tumor necrosis factor inhibitors. Results from PSUMMIT 1 showed that at week 24, 42% and 50% of patients receiving ustekinumab

45 and 90 mg, respectively, achieved at least 20% improvement in signs and symptoms, according to the American College of Rheumatology criteria (ACR20), the primary endpoint for both studies. In PSUMMIT II, 44% of those in both dosing groups achieved ACR20 at week 24. Ustekinumab also improved soft-tissue components of the disease, including dactylitis, enthesitis and skin component, as measured by Psoriasis Area and Severity Index score (PASI) 75. Data from the PSUMMIT I study were recently published in The Lancett (2013;382:780-789). The recommended dosing for ustekinumab is 45 mg subcutaneously at weeks 0 and 4, and then every 12 weeks thereafter. For patients with comorbid moderate to severe plaque psoriasis and who weigh more than 220 pounds, the recommended dose is 90 mg subcutaneously at weeks 0 and 4, and then every 12 weeks thereafter. It can be used alone or in combination with methotrexate. FDA approval of certolizumab for active PsA is based on data from the ongoing Phase III RAPID-PsA study of 409 patients with active and progressive

Perjeta Gains FDA Approval For Early-Stage Breast Cancer

he FDA has approved a first-line chemotherapy for preoperative early-stage breast cancer, Genentech announced in a statement on Sept. 30. Pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) is the first breast cancer treatment approved for use in a neoadjuvant setting. Pertuzumab also is the first drug to gain accelerated approval using pathologic complete response (pCR) data. “A new approval pathway has made Perjeta available to people with HER2-positive early breast cancer several years earlier than previously possible,” said Hal Barron, MD, chief medical officer of Genentech. “Together with the FDA, we’ve charted new territory.” In 2012, the FDA approved pertuzumab for metastatic, late-stage HER2-positive breast cancer. Pertuzumab now also is intended for patients with HER2positive early-stage, inflammatory or locally advanced breast cancer who are at risk for metastasis, relapse or death. Neoadjuvant therapy with pertuzumab can range from nine to 18 weeks (three to six cycles), and according to a Genentech representative, the cost of three to six cycles of pertuzumab plus trastuzumab will be an estimated $27,000 to $49,000. “We are seeing a significant shift in the treatment paradigm for early-stage breast cancer,” said Richard Pazdur, MD, the director of the FDA’s Office of Hematology and Oncology Products, in a press release. “By making effective therapies available to high-risk patients in the earliest disease setting, we may delay or prevent cancer recurrences.” The FDA based its approval on the results of a multicenter randomized Phase II trial, NEOSPHERE (Neoadjuvant Study of Pertuzumab and Herceptin in an Early Regimen Evaluation). Patients with HER2-positive early-stage, inflammatory or locally advanced breast cancer (N=417) were randomly assigned a 12-week regimen of one of four treatments: pertuzumab plus docetaxel; pertuzumab plus trastuzumab; trastuzumab plus docetaxel; or pertuzumab plus trastuzumab and docetaxel. The primary end point of NEOSPHERE was the lack of detectable tumors in breast and lymph node tissue, or pCR. About 39% of patients receiving pertuzumab plus trastuzumab and docetaxel—the most efficacious treatment—achieved pCR, followed by 21% of patients who received trastuzumab and docetaxel (P=0.0063). In the NEOSPHERE trial, adverse events included diarrhea, hair loss, nausea and a decrease in white blood cells. Anaphylaxis, decreased cardiac function, hypersensitivity and infusion-related reactions were other serious side effects. Additionally, the labeling for pertuzumab includes a warning that if it is used during pregnancy, it may cause birth defects or fetal death. The National Cancer Institute estimates that in 2013 there will be 232,300 new diagnoses of breast cancer and 39,600 women will die from the disease. Increased levels of HER2 protein are found in about 20% of breast cancer cases. —Ben Guarino

adult-onset PsA. Patients received a loading dose of certolizumab 400 mg at weeks 0, 2 and 4, or placebo, followed by either certolizumab 200 mg every other week or 400 mg every four weeks, or placebo every other week. Patients were evaluated for signs and symptoms of PsA using the ACR20 response at 12 weeks, and for structural damage using the modified Total Sharp Score (mTSS) at 24 weeks. ACR20, as well as ACR50 and ACR70 response rates at weeks 12 and 24 were higher for each certolizumab dose than for placebo. Certolizumab also resulted in improvement in skin manifestations in patients with PsA. However, the safety and efficacy of certolizumab in the treatment of patients with plaque psoriasis has not been established. Adverse events occurred in 62% of patients in the certolizumab group (combined dose) compared with 68% of patients in the placebo group. Serious adverse events occurred in 7% of patients in the certolizumab group (combined doses) and in 4% of patients in the placebo group. —Based on press releases from Janssen and UCB.

Two New Drugs Granted FDA Approval For Treatment of Metastatic Melanoma

he FDA has approved two new drugs for the treatment of skin cancer, both from GlaxoSmithKline: dabrafenib (Tafinlar) and trametinib (Mekinist). According to the agency, both drugs are approved for treatment of adult patients with unresectable or metastatic melanoma with BRAF F V600E mutation; in addition, trametinib is approved for patients with BRAF F V600K mutation. Also approved was a companion diagnostic test, the THxID BRAF test (bioMérieux), to help determine if a patient’s melanoma cells have the designated BRAF mutations. “The co-approval of Tafinlar and Mekinist and the … companion diagnostic for BRAF F mutation detection demonstrates the commitment of pharmaceutical and diagnostic partners to develop products that detect and target the molecular drivers of cancer,” Alberto Gutierrez, PhD, the director of the Office of In Vitro Diagnostic Devices and Radiological Health in the FDA’s Center for Devices and Radiological Health, in Silver Spring, Md., said in a statement. According to the FDA and GlaxoSmithKline, dabrafenib’s approval is based on an open-label trial in which 250 patients with BRAF F V600E mutation–positive metastatic or unresectable melanoma were randomized to receive either dabrafenib or the chemotherapy drug dacarbazine. Progression-free survival (PFS) was significantly higher in patients treated with dabrafenib than dacarbazine (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.20-0.54; P<0.0001), with dabrafenib prolonging PFS by 2.4 months more than dacarbazine. Trametinib’s approval is based on an open-label study of 322 patients with metastatic or unresectable melanoma and a BRAF F V600E or V600K mutation. There was a significant increase in PFS in patients treated with trametinib compared with chemotherapy (HR, 0.47; 95% CI, 0.34-0.65; P<0.0001), with trametinib prolonging PFS by 3.3 months more than chemotherapy. The most common adverse events (AEs) associated with dabrafenib (a BRAF F inhibitor) included hyperkeratosis, headache, fever, joint pain, noncancerous skin tumors, hair loss and hand-foot syndrome. The most serious AEs included an increased risk for cutaneous squamous cell carcinoma, increased blood sugar levels and severe fevers (potentially complicated by hypotension, shaking chills, dehydration or renal failure). Common AEs associated with trametinib (a MEK K inhibitor) included rash, diarrhea, peripheral edema, and skin breakouts resembling acne. The most serious AEs included heart failure, lung inflammation, skin infections and loss of vision. Both dabrafenib and trametinib carry the potential to cause fetal harm and infertility. —George Ochoa

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