June/July 2015 by McMahon Group

Bridging the gap between the hospital and alternate-site care Volume 4 • Number 3 • June/July 2015 • specialtypharmacycontinuum.com

‘An accident waiting to happen’ Up Front

HRSA releases new rules on penalties for 340B overcharging.

Operations & Mgmt

Cold Chain Crackdown Looms: Are You Ready?

Are integrated health networks the next hot SP model?

Policy

7 9

Biosimilars still face major hurdles in U.S. Pharmacist provider status gains traction

Clinical

10 18

$10k-a-year statin drugs are coming; will payors push back?

Technology

Disease State Spotlight

A Specialty Pharmacy Approach To Managing Rheumatoid Arthritis See page 12

Las Vegas—Orphan drugs are growing at nearly three times the rate of small-molecule medications—a welcome trend, given the historical paucity of effective treatments for the potentially life-threatening disorders targeted by these small-run pharmaceuticals, experts noted during the 2015 Armada Specialty Pharmacy Summit. Duchenne muscular dystrophy (DMD) is a case in point. “If there was ever a disease that has an unmet medical need, it’s this,” said Michael Einodshofer, RPh, MBA, the senior director of specialty strategy and innovation at Walgreens Specialty Pharmacy. “These children see ORPHAN DRUGS, page 14

ASCO report: Breakthroughs in melanoma and multiple myeloma.

ArmadaOne workflow platform streamlines data capture.

Orphan Drug Growth a Boon For Patients

Oral Chemo Rx Puts Spotlight On SP’s Value

Las Vegas—Oversight of cold chain shipping and monitoring is likely to become more rigorous in the near future, experts predicted at a best practices session on the topic during the Armada Specialty Pharmacy Summit. “The complexity of the supply chain has increased dramatically over the past five to 10 years,” said Barbara Unger, the president of Unger Consulting and former head of the GMP intelligence program at Amgen. “Materials now pass through dozens of hands and move halfway around the world. Historically, it’s been that last mile when products are most at risk.” Now, however, product integrity problems can arise much earlier in the distribution chain, Ms. Unger noted. “Many raw materials may be temperature-sensitive in such a way that they pass specs when we see them,” she said, “but they’re still degraded to the point that when they get into a drug product, their stability will be shortened, resulting in expensive recalls.” Bill Bailey, RPh, the president of PraxisRx Specialty Pharmacy, called cold chain an “accident waiting to happen. There have been too many packages shipped in good faith based on ‘certification’ of containers. Patients want another layer of assurance.” URAC’s Specialty Pharmacy Accreditation version 3.0 includes a new standard specific to the cold chain process—PHARM-OP 7: “Cold Chain Distribution: Process

San Diego—Specialty pharmacy must do a better job of promoting its value to oncology stakeholders, experts agreed at the 2015 annual meeting of the Academy of Managed Care Pharmacy. “Specialty pharmacy is in a unique position at the crossroads of the ‘four Ps’: providers, patients, payors and pharma,” said Mike Ellis, BSPharm, the corporate vice president of Walgreens Specialty Pharmacy and Infusion Services. “This is particularly important in oncology because of the impact of the new oral therapies.” The same number of oral chemotherapy agents was introduced in the nine years between 2004 and 2013 (27)

see COLD CHAIN, page 8

see ORAL CHEMO, page 17

Now Available

FDA Approval

Specialty Pharmacy Continuum iPad App

Medi-Dose/EPS Inc. has released additional Metric Only Oral Dispensers. See page 19

NEW

NOW INTRODUCING

CONVENIENCE WITH FEWER VIALS

40 g VIAL

Avoid potential IG waste—With the widest range of vial sizes, dispense IG according to prescription 1 g 2.5 g 5 g 10 g 20 g 40 g Important Safety Information

Visit gamunex-c.com to learn more.

GAMUNEX®-C (immune globulin injection [human], 10% caprylate/chromatography purified) is indicated for the treatment of primary humoral immunodeficiency disease (PIDD), idiopathic thrombocytopenic purpura (ITP), and chronic inflammatory demyelinating polyneuropathy (CIDP). Thrombosis may occur with immune globulin products, including GAMUNEX-C. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity, and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors. For patients at risk of thrombosis, administer GAMUNEX-C at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin intravenous (IVIG) 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 IVIG 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 patients who have had an anaphylactic or severe systemic reaction to the administration of human immune globulin. It is contraindicated in IgA-deficient patients with antibodies against IgA and history of hypersensitivity. Severe hypersensitivity reactions may occur with IVIG products, including GAMUNEX-C. In case of hypersensitivity, discontinue GAMUNEX-C infusion immediately and institute appropriate treatment. Monitor renal function, including blood urea nitrogen (BUN), serum creatinine, and urine output in patients at risk of developing acute renal failure. Hyperproteinemia, increased serum viscosity, and hyponatremia may occur in patients receiving IVIG treatment, including GAMUNEX-C. There have been reports of noncardiogenic pulmonary edema (transfusion-related acute lung injury [TRALI]), hemolytic anemia, and aseptic meningitis in patients administered with IVIG, including GAMUNEX-C. 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. Because GAMUNEX-C is made from human blood, it may carry a risk of transmitting infectious agents, eg, viruses, and, theoretically, the CreutzfeldtJakob disease (CJD) agent. Do not administer GAMUNEX-C subcutaneously in patients with ITP because of the risk of hematoma formation. 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 BUN and serum creatinine, before the initial infusion of GAMUNEX-C and at appropriate intervals thereafter. 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, because of the potentially increased risk of thrombosis. If signs and/or symptoms of hemolysis are present after an infusion of GAMUNEX-C, perform appropriate laboratory testing for confirmation. If TRALI is suspected, perform appropriate tests for the presence of antineutrophil antibodies and anti-HLA antibodies in both the product and patient’s serum. 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 PIDD) and infusion-site reactions, headache, fatigue, arthralgia and pyrexia with subcutaneous use (in PIDD); and headache, vomiting, fever, nausea, back pain, and rash (in ITP). The most serious adverse reactions in clinical studies were pulmonary embolism (PE) in 1 subject with a history of PE (in CIDP), an exacerbation of autoimmune pure red cell aplasia in 1 subject (in PIDD), and myocarditis in 1 subject that occurred 50 days post-study drug infusion and was not considered drug related (in ITP). © 2014 Grifols Inc.

October 2014

GX239-1014

Please see brief summary of GAMUNEX-C full Prescribing Information on adjacent page.

GAMUNEXÂŽ-C

C ?6+8685:+/4+3/' =/:. 8+9;2:'4: ).'4-+9 /4 9+8;3 </9)59/:? '4* +2+):852?:+ /3('2'4)+9 3'? 5));8 /4 6':/+4:9 8+)+/</4- # :.+8'6? Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified C !.853(59/9 .'9 5));88+* /4 6':/+4:9 8+)+/</4- # :.+8'6? 54/:58 6':/+4:9 =/:. 145=4 8/91 ,'):589 ,58 :.853(59/9 )549/*+8 HIGHLIGHTS OF PRESCRIBING INFORMATION ('9+2/4+ '99+993+4: 5, (255* </9)59/:? ,58 :.59+ ': 8/91 5, .?6+8 </9)59/:? These highlights do not include all the information needed to use GAMUNEXÂŽ-C safely and effectively. See full prescribing C 9+6:/) +4/4-/:/9 ?4*853+ .'9 (++4 8+658:+* =/:. information for GAMUNEX-C. " $ '4* 5:.+8 # :8+':3+4:9 +96+)/'22? =/:. ./-. *59+9 58 8'6/* /4,;9/54 GAMUNEXÂŽ-C, [Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified] C +352?:/) '4+3/' )'4 *+<+256 9;(9+7;+4: :5 # :.+8'6? *;+ :5 +4.'4)+* 9+7;+9:8':/54 54/:58 6':/+4:9 ,58 .+352?9/9 '4* Initial U.S. Approval: 2003 .+352?:/) '4+3/' WARNING: THROMBOSIS, RENAL DYSFUNCTION C 54/:58 6':/+4:9 ,58 6;2354'8? '*<+89+ 8+'):/549 :8'49,;9/54 and ACUTE RENAL FAILURE 8+2':+* ');:+ 2;4- /40;8? %! & See full prescribing information for complete boxed warning. C #52;3+ 5<+825'* E $3=:8-:>4> 8,y occur with immune globulin products, including GAMUNEX-C. Risk factors may include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity, and cardiovascular risk factors.

E := ;,?409?> at risk of thrombosis, administer GAMUNEX-C at the minimum dose and infusion rate practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. E "09,7 /Csfunction, acute renal failure, osmotic nephrosis, and death may occur with immune globulin intravenous (IGIV) products in predisposed patients. E "09,7 /Csfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose. GAMUNEX-C does not contain sucrose. E := ;,?409?> at risk of renal dysfunction or failure, administer GAMUNEX-C at the minimum concentration available and the minimum infusion rate practicable.

C " $ /9 3'*+ ,853 .;3'4 62'93' '4* 3'? )54:'/4 /4,+):/5;9 '-+4:9 + - </8;9+9 '4* :.+58+:/)'22? :.+ 8+;:@,+2*: '15( */9+'9+ '-+4: C " $ /9 45: '6685<+* ,58 9;();:'4+5;9 ;9+ /4 ! 6':/+4:9 ;+ :5 ' 65:+4:/'2 8/91 5, .+3':53' ,583':/54 *5 45: '*3/4/9:+8 " $ 9;();:'4+5;92? /4 6':/+4:9 =/:. ! C '99/<+ :8'49,+8 5, '4:/(5*/+9 3'? )54,5;4* 9+8525-/) :+9:/4- ----------------------------ADVERSE REACTIONS ---------------------------+8/5;9 '*<+89+ 8+'):/549 =./). 5));88+* /4 :.+ )2/4/)'2 :8/'29 =+8+ '4 +>')+8(':/54 5, ';:5/33;4+ 6;8+ 8+* )+22 '62'9/' /4 54+ 9;(0+): '4* 6;2354'8? +3(52/93 /4 54+ 9;(0+): =/:. ' ./9:58? 5, !.+ 359: )53354 '*<+89+ 8+'):/549 5(9+8<+* /4 âą&#x2013; 6':/+4:9 =+8+ PI 4tra<enous +'*').+ )5;-. /40+):/54 9/:+ 8+'):/54 4';9+' 6.'8?4-/:/9 '4* ;8:/)'8/' ;();:'4+5;9 4,;9/54 9/:+ 8+'):/549 .+'*').+ ,':/-;+ '8:.8'2-/' '4* 6?8+>/' ITP +'*').+ <53/:/4- ,+<+8 4';9+' (')1 6'/4 '4* 8'9. CIDP +'*').+ ,+<+8 )./229 .?6+8:+49/54 8'9. 4';9+' '4* '9:.+4/'

To report SUSPECTED ADVERSE REACTIONS, contact Grifols Therapeutics Inc. at 1-800-520-2807 or FDA at 1-800-FDA-1088 or GAMUNEX-C is an immune globulin injection (human), 10% liquid www.fda.gov/medwatch. indicated for treatment of: ----------------------------DRUG INTERACTIONS ---------------------------C 8/3'8? ;358'2 33;45*+A)/+4)? C !.+ 6'99/<+ :8'49,+8 5, '4:/(5*/+9 3'? :8'49/+4:2? /4:+8,+8+ =/:. C */56':./) !.853(5)?:56+4/) ;86;8' ! :.+ 8+96549+ :5 2/<+ </8'2 <'))/4+9 9;). '9 3+'92+9 3;369 '4* C .854/) 4B'33':58? +3?+2/4':/4- 52?4+;856':.? 8;(+22' --------------------------INDICATIONS AND USAGE -------------------------

----------------------------CONTRAINDICATIONS ----------------------------

---------------------USE IN SPECIFIC POPULATIONS ---------------------

C 4'6.?2'):/) 58 9+<+8+ 9?9:+3/) 8+'):/549 :5 .;3'4 C immunoglobulin C C - *+A)/+4: 6':/+4:9 =/:. '4:/(5*/+9 '-'/49: - '4* ' ./9:58? 5, .?6+89+49/:/</:?

8+-4'4)? 45 .;3'4 58 '4/3'2 *':' "9+ 542? /, )2+'82? 4++*+* +8/':8/) 4 6':/+4:9 5<+8 ?+'89 5, '-+ *5 45: +>)++* :.+ recommended dose, and infuse GAMUNEX-C at the minimum /4,;9/54 8':+ 68'):/)'(2+

----------------------WARNINGS AND PRECAUTIONS---------------------C - *+A)/+4: 6':/+4:9 =/:. '4:/(5*/+9 '-'/49: - '8+ ': -8+':+8 8/91 5, *+<+256/4- 9+<+8+ .?6+89+49/:/</:? '4* '4'6.?2'):/) 8+'):/549 '<+ +6/4+6.8/4+ '<'/2'(2+ /33+*/':+2? :5 :8+': '4? ');:+ 9+<+8+ .?6+89+49/:/</:? 8+'):/549 C 54/:58 8+4'2 ,;4):/54 /4)2;*/4- (255* ;8+' 4/:85-+4 9+8;3 8/,529 !.+8'6+;:/)9 4) )8+':/4/4+ '4* ;8/4+ 5;:6;: /4 6':/+4:9 ': 8/91 5, *+<+256/4- ');:+ +9+'8). !8/'4-2+ '81 " 8+4'2 ,'/2;8+ " /)+49+ 5

3036439/3036440-BS Revised: 7/2014

Specialty Pharmacy Continuum • June/July 2015

UP FRONT

More Oversight of 340B Program Looms

Only on the Web Visit us online for Web-only content. Links to the articles below can be found at SpecialtyPharmacyContinuum.com/webex0715 or by scaning the adjacent QR code.

Getting the Most From MHA Software

art 2 of our look at Managed Health Care Associates Inc.’s Clinical Therapy Management software focuses on the systems’s robust reporting features.

The Best Exotic Sovaldi Hotel?

ravel medicine isn’t only for facelifts: Patients are starting to travel overseas to buy hepatitis C medications on the cheap.

More Evidence Of Specialty Pharm Growth

x drug spending is up nearly 10% among Blue Cross Blue Shield companies. Guess which drug class is responsible?

he 340B Drug Pricing Program is undergoing a transformation. Some in Congress are trying to scale back or significantly reduce the program, according to the American Hospital Association, which opposes these actions. Others are trying to hold participants accountable. Along these lines, in mid-June, the Health Resources and Services Administration (HRSA) placed a notice in the Federal Registerr regarding the calculation of the 340B ceiling price and the imposition of civil monetary penalities. According to the proposal, manufacturers that intentionally overcharge 340B covered entities will be subject to fines of not more than $5,000 for each “instance.” Later this year, the HRSA is also expected to include a process for manufacturers to issue refunds to covered entities in case of an overcharge, and a process to calculate and validate 340B ceiling prices, according to Leah Ralph, manager of provider economics and public policy for the Association of Community Cancer Centers (ACCC). “We still need clear, comprehensive rules about how the program should work,” she said. Additionally, “we need clear definitions of what [an eligible] patient and a covered entity is, to be sure that our members can remain compliant in the program.” Last November, HRSA withdrew the “mega rule” it had submitted to the Office of Mangement and Budget, which was expected to cover the definition of an eligible patient, as well as the compliance requirements for contract pharmacy arrangements, hospital eligibility criteria and the eligibility of off-site facilities. The withdrawal happened after a federal district court in May last year decided that HRSA’s rulemaking authority for the 340B program is limited to specified areas. Meanwhile, a U.S. Government Accountability Office report, issued March 24, noted that HRSA in fiscal year 2012 implemented two of GAO’s four recommendations from 2011 “to provide reasonable assurance that program participants could comply with the program.” Some critics of the 340B program are calling for its abolishment—a position that makes little sense to Ernest R. Anderson Jr., MS, RPh, a consultant in Brockton, Mass., who attended the ACCC meeting. “One of the things I find remarkable about 340B in Congress is that politicians wonder how an institution can charge for drugs at their regular fees and still get discounts,” Mr. Anderson said. “It shows they don’t understand 340B at all. If we didn’t have 340B, we would have had a lot of hospitals go out of business.” —Karen Blum

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Volume 4 • Number 3 • June/July 2015

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Specialty Pharmacy Continuum • June/July 2015

OPERATIONS & MANAGEMENT

IHNs Pick Up Steam; Stakeholders Take Notice San Diego—The rise of integrated health networks (IHNs) has raised a question in some specialty pharmacy circles: Are these large entities more capable than traditional SP providers when it comes to delivering high-quality, cost-effective patient care? How about data aggregation and reporting and the other key requirements of operatingg effectivelyy in this competitive p space? p Kevin Colgan, BS, MA, FASHP, associate vice president of specialty pharmacy, University Health System m Consortium m (UHC) in Chicago, is und derstandably on the “IHNs-do-it-better” side of the debate. Their expaansive scope and patient bases enable tighter control of speccialty pharmacy services and related r costs, as well as options to offer their own group health plans p for managing population rissk, Mr. Colgan said during the 2015 annual meeting of the Acaademy of Managed Care Pharmaccy. There are other imporrtant differences between n the IHN and traditionall specialty pharmacy approach, he noted. For example, unlike established players, “IHNs are organized within an integrated care model with residency-trained and board-certified clinical pharmacists who often work within the specialty clinic using a common medical record system,” he explained. IHNs, he added, are equipped to track and evaluate treatment outcomes, allowing them to gauge the true value of a particular specialty pharmacy therapy, not just the cost. IHNs also feature a team approach to medication management, with the clinical pharmacist playing a prominent role. In a typical scenario, the patient’s care team, working together, initiates

the prescription, and “the pharmacist has an equal say as to what medications should be used,” Mr. Colgan said. Sometimes that leads to “constructive arguments” among team members, but the result is the most appropriate therapy decision. Physicians also introduce the team’s pharmacist to patients during rounds to better explain their medication therapy and answer questions. “That’s how we start a patient, and it’s typical of what you see in an integrated care model,” he said. An IHN’s benefits also include gathering outcomes data that allow quantitative evaluation of the efficacy and value of a given therapy, faster preauthorization of reimbursement approval and faster treat-

2013 (N=91)

2014 (N=70)

50 43

Health plans, %

38 36

31 26

10 0

the EMD Serono Specialty Digest, 10th Edition, issued in 2014, 33% of patients were found to be non-adherent to oral cancer medications, he noted. “The non-adherence piece concerns us all,” Mr. Colgan said. “That’s untenable. We need better systems in place no matter what the site of care.” When a specialty pharmacy was introduced into the hepatology, gastroenterology, rheumatology and multiple sclerosis clinics at Rush University Medical Center while Mr. Colgan was the system’s corporate director of pharmacy, he noted, the therapy abandonment rate fell to near zero. “We found patients who stopped therapy or never got started; they had gotten lost in the system,” he said. “[The impact of the pharmacy] was more substantial than I ever thought it would be. I don’t know of a patient we took care of who abandoned therapy.”

Partnering on Site of Care

ment initiation, Mr. Colgan said. He also cited drug adherence as an important consideration. High rates of therapy abandonment and non-adherence, he noted, are an issue for specialty pharmacy (although compliance challenges can be found in all market segments). g ) Accordingg to data cited in

Currently implement

Plan to implement

Figure. Site-of-care strategy. Source: EMD Serono Specialty Digest, 11th Edition

No plans to implement

Obtaining the best outcomes in specialty pharmacy isn’t just a question of who provides the care—it also can hinge on where that care is provided. That’s why a strategy known as site of care (SOC) optimization has become such an important tool, Mr. Colgan noted. In terms of cost, outpatient clinics are considered the most expensive site for care provision, while physicians’ offices and at-home care constitute the lower end of the cost spectrum, he explained. “When I look at the overall value equation and [improved] outcomes versus total cost of care, not just the drug expense, the HMOs and IHNs bend the cost curve the best, and they provide the most value.”

Still, there can be common ground between IHNs and established players in the specialty pharmacy space, especially when it comes to implementing SOC programs. Drug manufacturers and/or payors often use these programs to lower the cost of high-ticket medications. For example, Johnson & Johnson sought to rreduce the high cost of administering infliximab i (Remicade), which patients o often receive at hospital outpatient infu usion centers. Because competing druggs in the same niche can be self-aadministered at home, inflixim mab was at a clear disadvaantage. So Johnson & Johnso on teamed up with Walgreens and negotiated with health pllans to allow administration of the drrug at Walgreens’ infusion suittes at a significant discountt, Mr. Colgan noted. A rrecent industry survey (Figu ure) found that 31% of health plans implement an SOC strategy; m aanother 43% plan to implement one ((EMD Serono Specialty Digest, 11th Edition, issued in 2015).

Walgreens’ Take Michael T. Einodshofer, RPh, MBA, the senior director of specialty strategy and innovation at Walgreens, explained some of the impetus behind SOC programs. “We work closely with manufacturers, providers and insurers to improve access to medications and help lower health care costs,” he told Specialty Pharmacy Continuum. To accomplish those goals, he noted, “we have been flexible based on [SOC] requirements.” As for the criteria that should be used to select the best site of care, “the appropriate care setting varies by the individual patient,” Mr. Einodshofer said. “It’s important to evaluate the most clinically appropriate setting for each patient while also considering cost-effectiveness.” Asked to comment on the larger question of which player—traditional SP providers or IHNs—are best equipped to meet all the needs of specialty pharmacy patients and payors, Mr. Einodshofer chose to focus on the capabilities his own company brings to the table. “Our expertise in clinical support services as well as pharmacy operations, including billing, shipping and handling, positions us to continue to deliver the standard of care desired from those managing complex and rare conditions.” Several other top-10 specialty pharmacy providers declined to comment on Mr. Colgan’s views on the relative strengths and weaknesses of the various players in this market segment. —Steve Frandzel

Specialty Pharmacy Continuum • June/July 2015

POLICY

Jumping Hurdles To Bring Biosimilars to U.S. Market Philadelphia—Some of the largest pharmaceutical companies—those that already manufacture biologics as well as several new entrants—are interested in breaking into the lucrative U.S. biosimilar market. However, the hurdles they face in launching these products means that American patients might not actually see any biosimilars for years. Experts at the Biosimilars 20/20: A Look into the Future meeting, presented by the Specialty Pharma Education Center (SPEC) in partnership with the Specialty Pharma Journal, cited multiple barriers to biosimilars adoption that can occur before and after approval. Some of these barriers are general to the global market, while some are unique to the United States, they said.

by the

numbers

(and will typically be offered for future biosimilar approvals). “You cannot clinically test your product into biosimilarity,” said Aaron “Ronny” Gal, PhD, a senior analyst at Sanford

C. Bernstein & Co., a research and investing firm headquartered in New York City. The analytics are more relevant because, armed with such evidence, manufacturers can demonstrate whether the

products are highly similar or if there is a difference between the biosimilar and the reference product. Clinical trials are not useful for evaluating biosimilars because they will not distinguish between drugs with different mechanisms of action but the same clinical response, Dr. Gal said. Physicians on FDA advisory panels reviewing biosimilars must be taught how to weigh the evidence concerning see BIOSIMILAR, page 8

You can see the difference.

U.S. Daily Spend $45

daily cost | Average of a U.S. biologic

Average daily cost | of a chemical drug

One of the first hurdles occurs during the FDA approval process. Unlike chemical drugs, biosimilars are not approved based on clinical trial data. Rather, they are assessed based on data showing that the biosimilar is highly similar to, and has no clinically meaningful differences in safety and efficacy from, the reference product. Although small clinical studies are done, they are designed simply to confirm biosimilarity and to rule out any unusual immune responses.

A Change of Mindset However, physicians who sit on FDA advisory panels, as well as those who would prescribe biosimilars, are used to reviewing clinical trial data before making decisions about the proper use of a drug under review. At the FDA advisory panel meeting for Zarxio (filgrastimsndz, Sandoz, a biosimilar of Amgen’s Neupogen), the first biosimilar approved in the United States, the panel gave a considerable amount of credence to the patient data that the company presented from its experience in Europe, rather than the analytical data that were offered

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Specialty Pharmacy Continu uum • June/July 2015

POLICY

COLD CHAIN continued from page 1

Controls and Monitoring System.” (URAC representatives declined to provide the full text of the standard to Specialty Pharmacy Continuum, stating that the standards are only provided to current clients.) The organization brought in cold chain engineers to develop the new standard, noted Heather Bonome, URAC’s director of pharmacy. “We are putting a lot more focus on the cold chain process, but are not prescriptive on what the temperature range has to be,” she said. “The standard calls for specialty pharmacies to collect data and develop a well-designed process, with a qualified visual control, to ensure … [products] that must be shipped cold remain cold. Patients need to know that they have a safe product.” Mr. Bailey said an increasing number of state regulatory and supervisory bodies, such as boards of pharmacy, have been inquiring about cold chain monitoring, with the Georgia Board of Pharmacy out in front on this topic, holding hearings just this spring. Jeff Scott, PharmD, the director of pharmacy at Advanced Care Scripts, attested to the company’s experience with a pilot external monitoring system using the TransTracker, a single-use device from TempTime Corporation that monitors temperature exposure during shipping. “We had been experiencing some product losses. We ship out of Orlando [Fla.], a warmer environment, and when patients call us saying that their package feels warm and they don’t feel comfortable taking the drug, we’re eating that cost,” Dr. Scott said. After piloting the TempTracker temperature monitors beginning in summer 2014, the company experienced a significant reduction in reships—so much so that it saved $7.50 per dollar spent on the trackers. Average call times were reduced from 11 to five minutes. “If the package arrives late, we just have to ask the patient, ‘Did your indicator change color or not?’ It gives both them and us a measure of confidence that the drug has not exceeded the safe temperature range.” Mr. Bailey put the cost of cold-chain equipment in perspective. “The average cost of an indicator is about $1.00 to $1.50, depending on volume,” he said. “When you weigh that against the $5,000 medication that is

BIOSIMILAR continued from page 7

biosimilarity, explained Gillian R. Woollett, MA, DrPhil, a senior vice president at the consulting firm Avalere Health LLC, headquartered in Washington, D.C. “They are developed based on a different regulatory paradigm from that used for originator biologics,” she explained. Another hurdle comes with intellectual property rights. Here, the competition really heats up. Originator companies continue to defend their patents against biosimilar entrants, attempting to litigate the death of the biosimilar before it can be brought to market. As part of the approval process, biosimilar companies must hand over all of their documentation to the originator companies—the so called “patent dance” that is unique for these products. Companies typically hold multiple pat-

ruined, it’s a pretty in nexpensive way of managing invento ory and savings.” Another large sp pecialty pharmacy, which Mr. Bailey d declined to name, saved nearly $1.5 miillion in a pilot trial of temperature indicators i with two o drugs, and is now ex xpanding the program m to its entire inventorry.

Lukewarm on Ex xternal Temp Control Not everyone in n the cold chain field d is convinced that external tempera-ture indicators are the t solution. Jean-Pieerre Emond, PhD, the chief operating officer of the Illuminatee Group, director of cold c chain research in thee ElectroOptical Systems Laboratory L at the Georgia Tech h Research Institute, in Atlanta,, and CEO of the cold chain technology development compaany Blueye LLC, suggested thaat temperature tags are not always rreliable. “It seems so obvio ous, to put a temperature indicator on the package, kage, but more guidelines need to be established and they need to be easier for the average customer to read,” Dr. Emond told Specialty Pharmacy Continuum. “There are no regulations or certifications for temperature tags to ensure they are accurate, where they should be placed, whether the ability to program short excursions (such as 5° above or below the temperature range) for a specific duration is acceptable or not, or whether the data are secure.” Regarding optimal placement, “you could place the tag at 20 different locations inside the package and you will get 20 different temperature results that may not be representative of the pharmaceutical product’s actual temperature,” he stressed. Additionally, “there are very good tags on the market but also bad ones. Which ones should be [chosen]?” He noted that key

ents for branded pharmaceuticals, and for biotech products there may be dozens if not hundreds of patents. Some are product-specific; some address the manufacturing process; and some are related to drug delivery systems. Although exclusivity of the reference product’s license might expire 10 to 12 years after the date of first licensure, the term for a drug patent can be as long as 20 years, according to U.S. patent law. In addition to turning over all its documentation to the originator, a biosimilar manufacturer must also by law give the originator six months’ warning that it is entering the market with a competing product. The innovator’s attorneys will carefully review the documents, looking for evidence that a patent has been violated, Dr. Gal said. Moreover, during that process, “innovators can go out and license additional patents of their products and you might be

factors in the quality of a tag include its acccuracy, ability to program temperrature excursions, battery life, samplling intervals and reliability. Dr. Emond, who o also spoke at the Georgia Board of Pharmacy hearing on cold chain mon nitoring on May 13, instead argued forr “qualifying” the packaging system itself, noting that the industry and the scientific commun nity have created tem mperature profiles and packaging qualification procedures and guidelines to protect teemperature-sensitive products. “The ship pers can customize p industtry-standard temperature profiles or create their own n through test shipments throughout the year, and desiggn a package that can with hstand more than those determined temperatures,” he explaained. “The package can be even designed to withstand extreme temperature abuse abuses during shipment to help ensure temperature maintenance.” Ideally, the package should be designed to withstand the exposure temperature for a set time, covering the time the lid is closed until it is delivered to the customer and opened, Dr. Emond noted. “If a package is supposed to be delivered in 36 hours,” he said, “make sure the package can maintain the right temperature for an extra 12 to 24 hours. Then a label on the package could say that it is good until this time on this date.” —Gina Shaw Dr. Emond reported that his company helps mailorder pharmacies, blood banks and food retailers with regulatory compliance. Mr. Bailey reported no relevant ﬁnancial conﬂicts of interest.

infringing them [as well].” This litigation could hold up a biosimilar’s entry into the market for years, Dr. Gal stressed. New patents are not the only grounds for litigation, he noted. Originators also pursue new indications and delivery systems that can increase the life of the originator product. Although Zarxio was not approved as an interchangeable product—meaning that currently treated patients can only be switched to the new product by their physician and not a pharmacist—it was initially approved for all the same uses as Neupogen. On March 30, 2015, however, the FDA approved the use of Neupogen to treat myelosuppressive doses of radiation (hematopoietic syndrome of acute radiation syndrome, or H-ARS). Consequently, Zarxio is no longer indicated for all the same uses, which could have implications for an FDA interchangeability designation, as well as for formulary manage-

ment and insurance reimbursement. Right now, “the biggest barrier is the lawyers,” said Steve Miller, MD, MBA, a senior vice president and chief medical officer at Express Scripts. On June 3, Amgen and Sandoz took a few more steps in the patent dance when they presented oral arguments in Federal Circuit Court. Amgen is appealing an earlier court’s ruling that Biologics Price Competition and Innovation Act patent provisions were optional. They are also disputing the timing of Sandoz’s notification of its intent to market a biosimilar, which was given when it filed its application with the FDA, rather than after the product was approved. At press time, the Circuit Court had not reached a decision in the appeal. —Marie Rosenthal Drs. Gal, Miller and Woollett reported no relevant ﬁnancial conﬂicts of interest.

Specialty Pharmacy Continuum • June/July 2015

POLICY

Provider Status Gains Ground Denver—Bills granting provider status to pharmacists are gathering momentum in Washington, according to Joe Hill, the director of federal legislative affairs at the American Society of Health-System Pharmacists (ASHP). “Provider status is the biggest issue facing [the profession],” Mr. Hill told Specialty Pharmacy News at the ASHP Summer meeting. He added that he was pleased with the progress that ASHP and other pharmacy organizations have made getting the legislation drafted and submitted to Congress. Two bills, one in the House and one in the Senate (H.R. 592/S. 314), have been introduced. “We are getting significant [bipartisan] support” for the legislation, Mr. Hill said. “Currently, we have 141 cosponsors to the House bill and 16 cosponsors for the Senate bill.” Much of the support comes from representatives of states where the medical need is greatest among their constituents. “A lot of people in rural areas have limited access to care and so they view these bills very favorably,” Mr. Hill said. Patients in such areas, he noted, often must travel several hours to see a doctor for a condition that could be managed by a pharmacist who is only 20 minutes away. If pharmacists gain provider status via the bills—which include a reimbursement component and other supportive measures—it is easy to see how the legislation could improve pharmacists’ ability to meet the needs of such patients, he noted. Although Mr. Hill said he believed the legislation has a “good shot” at becoming law, it still faces substantial challenges, not least of which is cost. Congress is reluctant to approve bills that increase Medicare expenditures, he noted, and traditionally, adding providers such as pharmacists to the program does boost short-term spending. The trick will be to show legislators that pharmacists can decrease costs in the long term by providing clinical services that are less expensive than those delivered by a physician. “[ASHP] is confident that downstream savings will indeed occur in the Medicare program” when pharmacists with provider status are added to the health care team, Mr. Hill said. Making that case to Congress, however, and addressing other fiscal concerns “is the biggest hurdle that we face this year” in terms of getting the provider status bills passed. Grassroots support could be the tipping point. “We need significant participation from pharmacists nationwide to ask their legislators to support the legislation and help us get this done.” That message was echoed by John Armitstead, MS, RPh, FASHP, the president-elect of ASHP, during his inaugu-

ral address at the Summer Meeting. “We all must get behind ASHP’s assertive advocacy in Congress and reach out to our own senators and representatives to make sure they know that pharmacists

can improve patient care,” Mr. Armitstead said. ASHP has developed online tools to streamline the advocacy process. Pharmacists can go to the member section of the ASHP website (http://goo.gl/fcirbN) and sign a letter that will automatically be sent to their representatives. The website also provides other grassroots activities

that could help get the bill passed. The American Pharmacists Association has also been a strong advocate of the provider status legislation. CEO Tom Menighan noted in a June 12 statement that the extensive number of cosponsors is “another milestone” in the legislation’s journey. He also urged pharmacists to show their support for the bills by contacting their elected officials. —Marie Rosenthal

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Specialty Pharmacy Continuum • June/July 2015

CLINICAL

PCSK9 Drugs May Usher Cardio Rx Into SP Arena Las Vegas—The looming, much-anticipated approval of the first two drugs in the novel class of PCSK9 inhibitors—monoclonal antibodies that target the cholesterol-regulating gene PCSK9’s protein product—will plunge a whole new group of providers and patients into the world of specialty pharmacy. The first two PCSK9 inhibitors, SanofiRegeneron’s alirocumab (Praluent) and Amgen’s evolocumab (Repatha), were recommended for approval in June by an FDA advisory committee. Both medications are expected to gain full FDA approval before Labor Day, speakers noted during a session on the specialty drug pipeline at the recent Armada Specialty Pharmacy Summit. Repatha will be offered as a biweekly 140-mg injection or a monthly injection of 420 mg, while Praluent will be offered in biweekly injections of 75 or 150 mg. Initially, the drugs are expected to be approved for familial hypercholesterolemia, which has an estimated

prevalence of one in 250 to 500 or about 620,000 individuals in the United States (Am ( Heart J 2014;168[6]:807811). But they also may be used and/or approved to treat some of the estimated 20% of patients with high cholesterol that does not respond sufficiently to statin drugs ((Arterioscler Thromb Vasc Biol 2015;35[4]:990-995), as well as those who cannot tolerate statins. Cardiologists and their patients with high cholesterol typically haven’t had much experience with specialty pharmacy, according to Amy Grogg, PharmD, the senior vice president of strategy and commercialization at AmerisourceBergen Specialty Group. “These physicians

Average Annual Cost of Therapy PCSK9 Inhibitors (Projected)

Annual Cost

$10,000 Statins

+4,000%

$230

Lowering LDL cholesterol: Statins vs. PCSK9 Inhibitors Statins

PCSK9

20%-45%

Up to 60%

Source: https://www.optum.com/thought-leadership/new-cholesterol-drugs.html

will need significant education, not just about the product, but also about specialty pharmacy,” she said. “They don’t live in this sphere and don’t typically deal with the specialty reimbursement structure very much.” It’s also much more challenging for manufacturers to conduct focused, personal outreach to this population, Dr. Grogg added. “When you’re dealing with a condition like multiple sclerosis or rheumatoid arthritis, if you can identify the top three prescribers in a market, you can send a pharmacist to educate them. But how do you winnow down to the top prescribers of cholesterol-lowering medication? We’re talking about massive numbers of practitioners versus very small, select, oneon-one conversations.” Moreover, the reimbursement structure for specialty medications will be somewhat foreign to cardiologists, Dr. Grogg suggested. “Will the manufacturers have a limited distribution network? Most cardiology groups have never lived in that space, with frequent prior authorizations and step edits.” Providers aren’t the only ones who will need education and support in this strange new world, said Ray Tancredi, RPh, MBA, CSP, the vice president of specialty pharmacy development at Walgreens. “For many cardiac patients, this will be their first exposure to specialty pharmacy. Their doctors’ offices won’t be as familiar as rheumatologists and neurologists with things like copay coupons and foundations. This suggests a great opportunity for partnership between specialty pharmacies and cardiology practices.” Cardiologists have dealt with prior authorizations and step edits for cholesterol management, but it’s been a while, said Joseph Saseen, PharmD, the vice chair of the Department of Clinical Pharmacy at Skaggs School of Pharmacy and Pharmaceutical Sciences at

the University of Colorado, in Denver. “At one time, the ARBs [angiotensin receptor blockers] had a lot of prior authorizations—even Crestor [rosuvastatin calcium] and Lipitor [atorvastatin] had them at one point. We sometimes still do see step edits for PPIs [proton pump inhibitors], although that’s decreased quite a bit. Cardiology practices have been down this road,” he said. “But this is going to be a biggerticket item, with tighter regulations and a more restrictive label.” That’s partly because PCSK9s represent an entirely new drug class, although the available data so far seem to indicate that these agents are very safe and well tolerated (with some concerns because it is a novel drug class). It’s also a significant cost issue. “The price point I’ve heard for these drugs is around $10,000 annually,” Barbara Wiggins, PharmD, a clinical pharmacy specialist in cardiology at the Medical University of South Carolina, in Charleston, told Specialty Pharmacy Continuum. “That cost is going to be a little bit of a shock to the cardiology world. We do have a couple of very high-cost drugs, like ivabradine [Corlanor, Amgen] for heart failure, which costs around $4,500 a year, but we’ve gotten to the point where so many of our drugs are so inexpensive, as little as $4 for a month’s supply. How do you justify the cost of a $10,000 agent when it’s very difficult to clearly define statin intolerance and so much of it is subjective?” With some 27% of U.S. adults aged 40 and over taking a statin, according to the National Health and Nutrition Examination Survey of 2003-2012, the numbers for “statin failure” could be very high indeed—and has payors worried. “The annual price for these drugs may not sound like too much when you’re hearing about $100,000 and $200,000 drugs, but the market

Specialty Pharmacy Continuum • June/July 2015

CLINICAL

may be much larger [for these new cardiology agents],” said Sarah Marche, a vice president of pharmacy markets at Highmark Inc., in Pittsburgh. Moreover, unlike the headline-generating hepatitis C drugs such as sofosbuvir (Sovaldi, Gilead), which are cures, these drugs would be taken indefinitely. “As a payor, it forces us to get aggressive in [determining] what are true statin failures?” Ms. Marche said. “Can we just take the doctor’s word for it? How do we know it will provide value for these patients?” The National Lipid Association has a fairly broad definition of statin intolerance, Dr. Saseen said. “They define it as the inability to tolerate two different statins, one of which is at the lowest approved starting dose [[J Clin Lipidol 2014;8,S78]. This could mean different things to different people. We have limited health care dollars, and statins have a long history of benefit, so we need to be prudent about who starts these drugs.”

‘The price point I’ve heard for these drugs is around $10,000 annually. That cost is going to be a little bit of a shock to the cardiology world.’ —Barbara Wiggins, PharmD to be the defining moment for these medications,” Dr. Wiggins said. She expects that the PCSK9 inhibitors will require cardiology practices to

increase resources devoted to patients’ insurance coverage. “I do a lot of the paperwork for the prior authorizations we do have now, and a lot of it [involves]

phone calls. Yes, there are times when we can get overwhelmed. We may have to allocate and redistribute our resources and have many people involved in getting the approvals, rather than just one or two. It’s difficult at this point to know how it’s all going to play out.” —Gina Shaw Dr. Saseen was a member of a multidisciplinary advisory board for education sponsored by Sanoﬁ-Regeneron. Dr. Wiggins serves as a consultant for Amgen.

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That said, there is significant potential benefit from PCSK9s for some patients, he acknowledged. “I saw a patient just the other day who had literally tried every single statin—seven different drugs—and did not tolerate every one. She has a baseline LDL [low-density lipoprotein] in the 200s, and to me, that is a patient who would qualify for these new medications. Of course, I don’t know if insurance companies will see it the same way.” The proof will be in the efficacy data, Dr. Wiggins said. “The utility is going to be there from the beginning, with a lot of patients who will need it, but at this point we still have only preliminary outcomes data.” Those have certainly been encouraging—showing about a 50% reduction in the risk for composite cardiovascular events for both evolocumab and alirocumab ((N Engl J Med d 2015;372:14891499 and 1500-1509)—but they represent only post hoc analysis. There are several major ongoing PCSK9 inhibitor trials (Sidebar). These trials are not expected to report full outcomes data until 2018. “That’s going

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Specialty Pharmacy Continuum • June/July 2015

CLINICAL

DISEASE STATE SPOTLIGHT

Managing Patients With Rheumatoid Arthritis Renee Baiano, PharmD Clinical Program Manager Walgreens Specialty Pharmacy Carnegie, Pennsylvania

In the United States, it is estimated that annual direct and indirect costs attributable to rheumatoid arthritis (RA) and other rheumatic conditions are approximately $128 billion.1 This burdensome disease affects approximately 0.5% to 1% of the general population.2 Early, aggressive treatment of RA can greatly improve outcomes. However, managing this chronic condition can be a challenge for providers and patients. Some barriers to controlling RA include therapy nonadherence, presence of comorbidities, and disease activity.3 Because there is no known cure for RA, the primary goal of therapy is to reach low disease activity or remission.3 Achieving this goal results in improved quality of life, prevention of new joint destruction, and reduced pain and inflammation.4 With the development of new medications and treatment guidelines urging early interventions, the outcomes for RA patients have drastically improved. Current treatments allow for proper management and improved clinical outcomes for a complex disease once known for causing debilitating deformities. Without treatment, the disease can cause pain, inflammation, and ultimately irreversible bone erosion. The specialty pharmacist plays a key role in educating the patient on the importance of following the prescribed treatment plan. Additionally, by counseling the patient about medication administration, side effects, and disease activity, the specialty pharmacist can help the patient best manage his or her disease.

An Autoimmune Disorder The most common type of autoimmune arthritis, RA affects at least 1.3 million U.S. adults.5 Of those affected, about 75% are women.5 Although RA can start at any age, it most commonly begins between the fourth and sixth decades of life.5 In RA, the body’s immune system mistakenly attacks the synovium, which is the tissue that lines the joints. This can lead to irreversible erosion of cartilage and bone. The small joints in the hands and feet are most commonly affected. Pain, stiffness, and swelling are usually worse in the morning and can last 30

Rheumatoid Arthritis: Patient Case FC is a 53-year-old man with a history of rheumatoid arthritis (RA). In 2008, he was prescribed the tumor necrosis factor (TNF) inhibitor adalimumab (Humira, AbbVie), and has been receiving monthly medication and supplies from Walgreens Specialty Pharmacy (WSP). When FC began receiving his medication and patient management support from WSP, his insurance copay/financial responsibility was more than $500 per month. At the initiation of therapy with WSP, the WSP insurance team researched several options to assist FC with his monthly financial expense and, through a copay assistance program, was able to decrease FC’s monthly outlay to $5. Every month—before each prescription refill—a WSP Patient Care Coordinator (PCC) contacts FC proactively. During these outreach assessments, the PCC, using the WSP proprietary disease management application Connected Care, will review if the patient missed any doses, experienced any disease-state flares in the past 30 days, and had any other adverse events. These scheduled monthly assessments promote medication adherence and facilitate patient-specific disease management requirements. Upon identification of any issues or concerns based on the Connected Care algorithms, the patient speaks with a WSP specialty-trained pharmacist. During a recent patient interaction prior to a scheduled refill, the WSP PCC, using the Connected Care application, identified that FC had missed several injections. The Connected Care algorithm prompted the patient to be transferred to a WSP pharmacist to discuss adherence, with the goal of uncovering any obstacles to adherence and providing the necessary support. During the pharmacist consultation, FC reported that he was recovering from an elbow injury, and his rheumatologist was treating him with oral prednisone to prevent a flare while holding his dose—a clinically appropriate reason for missing a dose, which was identified and entered into the patient’s record. During a subsequent patient assessment, FC indicated that he missed an injection due to insurance changes. He was counseled by a WSP specialty-trained pharmacist on the potential adverse effects of missing his dose. The patient was also provided support regarding his updated insurance benefits, and he was able to obtain his medication. Recently, FC mentioned he would prefer to use the prefilled syringe dosage form of his medication instead of the pen device. Based on this information, the WSP specialty-trained pharmacist contacted FC’s physician and obtained an updated prescription. Because of the collaborative efforts made by the staff at WSP, FC’s treating physician, and the patient, FC has been and remains adherent to his medication regimen. This case study demonstrates the key roles that a specialty pharmacy can have in assisting RA patients to manage their treatment.

minutes or longer after waking.5 Although RA may sound like a disease that exclusively affects the joints, it actually is a systemic inflammatory process. In addition to joint involvement, RA can present with symptoms such as fever, loss of appetite, and fatigue. The disease can manifest in other organs, including the lungs, blood vessels, eyes, and kidneys.6 One of the most common extra-articular manifestations of RA is the development of nodules—firm lumps under the skin—which present in up to 30% of patients.7 Early and aggressive therapy depends on an accurate diagnosis, which can be a challenge, in part because the symptoms of RA are often nonspecific.2 Additionally, there is no single test that can diagnose RA, and therefore diagnosis is based on physical symptoms, blood work results, and various examinations. Rheumatoid factor, an antibody found in about 80% of RA patients, and antibodies to cyclic citrullinated peptides, found in about 60% to 70% of RA patients, can be used to aid diagnosis.5 Also, RA patients often present with an elevated erythrocyte sedimentation rate and anemia.5 The physician may also perform radiographs, magnetic resonance imaging, and ultrasonography examinations to assess disease progression and measure the severity of the disease.5

Current RA Therapies Although the pathogenesis of RA is not completely understood, recent advances have allowed for targeted therapies that result in improved clinical outcomes. Cytokines, such as tumor necrosis factor (TNF)-α and various interleukins (ILs), are often found to play a key role in T-cell and B-cell proliferation and inducing an inflammatory response, which ultimately causes inflammation and joint damage.8 Biologic medications on the market today work to block the activity of these cytokines, as well as other immune response pathways. Treatment of RA is guided by disease duration, disease activity, and prognostic features. According to the American College of Rheumatology (ACR) RA treatment guidelines, the patient is categorized to have early or established RA based on how long disease symptoms have been present (<6 mo or >6 mo, respectively.)9 The disease activity is determined as low, moderate, or high according to a validated patient scale, such as the Patient Activity Score (PASII), Disease Activity Score in 28 joints, or Clinical Disease Activity Index. Lastly, the patient’s prognostic features are evaluated. Poor prognostic

Specialty Pharmacy Continuum • June/July 2015

CLINICAL

features include extra-articular disease, positive rheumatoid factor, positive anti–cyclic citrullinated peptide antibodies, bony erosions, and functional limitations.9 Tools to quantify functional limitations, such as the HAQ-II (Health Assessment Questionnaire), can assess a patient’s ability to participate in daily life activities. Review of all of these elements assists the rheumatologist in determining the appropriate therapy. Disease-modifying antirheumatic drugs (DMARDs) are the cornerstone of RA treatment. The ACR considers leflunomide, hydroxychloroquine, sulfasalazine, minocycline, and methotrexate as the primary nonbiologic DMARDs. These medications are often used as first-line monotherapy or combination therapy, depending on disease activity and prognosis.9 Methotrexate, which inhibits dihydrofolate reductase, is often the DMARD of choice due to efficacy rates and ability to slow radiographic progression.10 The entry of biologic DMARDs into the market delivered another treatment option to improve function and decrease disease progression. These medications target abnormalities of the immune system responsible for inflammation. Biologic DMARDs consist of TNF-α antagonists, IL-6 antagonists, IL-1 antagonists, and medications that modulate T cells and B cells and are administered by IV infusion or subcutaneous injection. Biologics are recommended by the ACR for patients who failed traditional nonbiologic DMARDs and, in some cases, as first-line therapy for more severe disease.9 Biologics are often used with the nonbiologic DMARDs. In fact, the PREMIER study, which compared the use of the biologic adalimumab (Humira, AbbVie) and methotrexate combination therapy with adalimumab or methotrexate monotherapy, showed that combination therapy significantly improved disease symptoms and progression.11 TNF-α antagonists are often the first biologics used in RA therapy. There are 5 FDA-approved TNF-α antagonists on the market for RA: adalimumab, certolizumab (Cimzia, UCB Pharma) etanercept (Enbrel, Amgen), infliximab (Remicade, Janssen Biotech), and golimumab (Simponi, Janssen Biotech). Medications in this class have a black box warning for infections, malignancy, and tuberculosis.12 Tocilizumab (Actemra, Genentech) is an IL-6 antagonist available as an IV infusion or a subcutaneous injection. It is important to monitor the absolute neutrophil and platelet counts, as well as liver function tests, in patients taking tocilizumab.10 The IL-1 antagonist on the market for RA is anakinra (Kineret, Sobi), a daily subcutaneous injection. Abatacept (Orencia, Bristol-Myers Squibb), which modulates T-cell activation, is available

Table. FDA-Approved Biologic Medications Indicated To Treat Rheumatoid Arthritis Mechanism of Action

Medication

Company

Available Forms

Dosage

TNF-α Inhibitor

Adalimumab (Humira)

AbbVie

Prefilled syringe, prefilled pen

SC: 40 mg every other week

Etanercept (Enbrel)

Amgen

Prefilled syringe, Sureclick pen, vials

SC: 50 mg weekly

Certolizumab (Cimzia)

UCB Pharma

Prefilled syringe, vials

SC induction: 400 mg at 0, 2, and 4 wk Maintenance: 200 mg every other week thereafter Maintenance alternative: 400 mg every 4 wk can be considered

Golimumab (Simponi)

Janssen Biotech

Prefilled syringe, Smartject autoinjector, vials (Simponi Aria)

SC: 50 mg every 4 wk

Infliximab (Remicade)

Janssen Biotech

Vials

IV induction: 3 mg/kg at 0, 2, and 6 wk Maintenance: 3 mg/kg every 8 wk thereafter

IL-1 antagonist

Anakinra (Kineret)

Sobi

Prefilled syringe

SC: 100 mg daily

IL-6 antagonist

Tocilizumab (Actemra)

Genentech

Prefilled syringe, vial

SC: Weight <100 kg: 162 mg every other week, followed by an increase to every week based on clinical response; weight ≥100 kg: 162 mg every week

IV induction: 2 mg/kg at 0 and 4 wk Maintenance: 2 mg/kg every 8 wk thereafter

IV: 4 mg/kg every 4 weeks followed by an increase to 8 mg/kg every 4 weeks based on clinical response Modulation of T-cell activation

Abatacept (Orencia)

Bristol-Myers Squibb

Prefilled syringe, vials

SC: 125 mg once weekly, may be initiated with or without an IV loading dose. If initiating with IV loading dose: Give a single IV loading dose (per body weight), followed by the first 125 mg SC injection within a day of the IV infusion IV: Induction: Initially then at 2 and 4 wk after the first infusion Maintenance: Every 4 wk thereafter. Weight <60 kg: 500 mg. Weight 60-100 kg: 750 mg. Weight >100 kg: 1,000 mg

Binding to CD20, depletion of B-cells

Rituximab (Rituxan)

Genentech

Vials

IV: 2 1,000-mg infusions separated by 2 wk. Subsequent courses should be administered every 24 wk or based on clinical evaluation, but not sooner than every 16 wk.

IV,, intravenous;; SC,, subcutaneous

as a subcutaneous injection and an IV infusion.10 Lastly, rituximab (Rituxan, Genentech) is a biologic available as an IV infusion. Rituximab has a black box warning for progressive multifocal leukoencephalopathy, which is an infection caused by the reactivation of the John Cunningham (JC) virus.10 In 2012, tofacitinib (Xeljanz, Pfizer) was approved by the FDA. Tofacitinib is an oral Janus kinase (JAK) inhibitor, indicated for moderately to severely active RA in patients who have had an inadequate response or intolerance to methotrexate.13

The Specialty Pharmacist’s Role: Improving Quality of Life Although evidence is clear that early, aggressive treatment is crucial in preventing irreversible joint damage in RA, medication adherence rates range from 30% to 80%.14 In addition to negatively affecting clinical outcomes, nonadherence has a major impact on health care

costs. There were more than 15,600 hospitalizations in 2009 among individuals with RA in the United States.2 When addressing adherence concerns with a patient, it is important to be mindful of some of the potential barriers that patients may face. Patient-driven undertreatment is one of the most common causes of nonadherence.3 It appears that patient concern lies more with the current status of the disease than with future disease control. Disease improvement is misinterpreted as not needing to take medication.3 This error in perception of a reduced need for medication and the fear of side effects are major factors to consider when counseling about compliance. Walgreens Specialty Pharmacy takes a proactive approach to encourage medication adherence. Monthly outreach assessments are conducted to follow up with the patient and schedule delivery of medication refills. During these proactive interactions, patients are assessed for missed doses as well as side effects

and disease flares through a propriety patient management platform—Connected Care. Any patient concern or identified issue leads to a system-generated, algorithm-based clinical escalation, and patients are transferred to a pharmacist for education and support with follow-up notification to the patient’s prescriber, if needed. By identifying nonadherence and other concerns, the specialty-trained pharmacist can provide the patient with the required patient-specific supportive care. The specialty pharmacist can play a key role in identifying opportunities for intervention with RA patients. For example, patients who cannot remember to take a weekly dose of their injection may benefit from switching to a medication that offers once-monthly dosing. Also, a pen device versus a prefilled syringe could be more appealing to a patient with a fear of needles. Additionally, pharmacists can help support see RA, page 16

Specialty Pharmacy Continuum • June/July 2015

CLINICAL

ORPHAN DRUGS continued from page 1

may die by their 20th birthday and have a very difficult last few years of life.” Very few treatment options have been available to treat DMD, “but we may actually see a drug approved” for the disorder in 2015, Mr. Einodshofer said (sidebar).

drugs used to treat larger patient populations,” Ms. Lima observed. Between 2012 and 2014, she added, orphan drugs went from 45% of specialty drug approvals (10 of 22) to 74% (20 of 27). Today, she noted, orphan drugs account for $176 billion in annual sales worldwide, and could account for 19% of total prescription drug sales by 2020.

‘You have to ask yourself if you can appropriately case-manage hundreds of new products that may come around in very rare diseases.’

by the

numbers

Sales 2018 Non-orp phan Drug gs

By 2018: Worldwide orphan drug sales forecast to be

$127 billion Compounded annual growth rate for orphan drugs will be

2x overall drug market.

Orph han Drug gs

—Michael Einodshofer, RPh, MBA Source: Biotech Now (http://goo.gl/UN9Tzh)

Hetty Lima, RPh, FASHP, who recently retired as vice president for specialty infusion services and rare diseases at Diplomat Specialty Pharmacy, is a keen watcher of the orphan drug class and offered Armada attendees a snapshot of the category’s recent growth. “Orphan drug sales in the United States are expected to grow at an annual rate of approximately 11% through 2020, versus a growth rate of about 4% for

That’s because the orphan pipeline is full to bursting. In 2014, the FDA granted orphan drug status to a total of 286 investigational compounds; by the end of May 2015, 168 compounds had achieved this status, putting the year on track for nearly 350 orphan designations, compared with 164 in 2009 (FDA Orphan Drug Product designation database, http://goo.gl/rF4owZ). “Currently, there are approximately

Orphans Looking for a Home Here are a few examples of rare diseases with drugs in the pipeline: Hypophosphatasia (HPP). This inherited, progressive disorder involves low levels of the alkaline phosphatase enzyme, and causes extremely brittle bones. By the time they reach adulthood, patients with this disease have usually had around 14 fractures. HPP can also cause severe organ damage; babies born with the condition have a 58% probability of death in their first year of life (Bone Abstracts (2014) 3 PP364). The severe form of the disease is estimated to affect one in every 300,000 people—or just over 1,000 people in the United States. In March, the FDA accepted priority review of Alexion’s biologics license application for asfotase alfa, a first-in-class enzyme replacement therapy for treatment of patients with infantile- and juvenile-onset HPP. The drug, which in trial results presented last fall at the American Society for Bone and Mineral Research 2014 annual meeting, significantly improved survival in pediatric patients, is expected to cost $200,000 per year. “Potential sales for this drug are estimated at $578 million by 2019,” Ms. Lima said. Duchenne muscular dystrophy (DMD). There are several drugs in the pipeline for DMD, the most severe form of muscular dystrophy, which affects as many as 10,000 children (primarily boys) in the United States. Investigational products include ataluren (Translarna, PTC Therapeutics), already approved in Europe, and the exon-skipping drugs drisapersen, in development by BioMarin, and eteplirsen from Sarepta. “The trials on these have been somewhat inconsistent, but they’re looking more positive now,” Mr. Einodshofer said, adding that the patient population that would be a target for DMD therapy is definitely limited. “These are very small numbers—if a health plan covers a million lives, they might have two to five children [with DMD] being prescribed one of these new agents,” he said. “But finding a way to pay for them is critical, because they are expected to be ultra-orphan trendbusters—well into the six-figure price point.” Lysosomal storage disorders (lipidoses). These inherited metabolic disorders involve the accumulation of harmful levels of lipids in cells and tissues. Approximately 50 lysosomal disorders have been identified, affecting one in 5,000 births or about 63,000 people totally. The most common of these, Gaucher’s disease, affects 5,700 people, and it’s the only one with multiple treatment options. Oral and IV enzyme replacement treatments for Gaucher’s, from Shire, Pfizer and Sanofi-Genzyme, cost in excess of $250,000 per year, Ms. Lima said. Two other lipidoses, Fabry disease and Pompe disease, have potential new treatments in Phase III trials. Thomson Reuters estimated that Biomarin’s BMN-701, for late-onset Pompe disease, could hit $163 million in sales by 2019, while Amicus’ Migalastat oral for Fabry disease could reach the $99 million mark, Ms. Lima said.

—G.S.

320 products in the late stage pipeline for rare diseases,” Mr. Einodshofer said. “If you’re a smaller specialty pharmacy, you have to think about balancing. Do you specialize in only some of those rare diseases and try to be an expert, while at the same time trying to manage the larger diseases like multiple sclerosis and rheumatoid arthritis? You have to ask yourself if you can appropriately casemanage hundreds of new products that may come around in very rare diseases.” This is particularly important since about 83% of orphan drug disorders qualify as “ultra-orphan”—that is, they affect fewer than 6,000 patients. (A total of 200,000 patients are deemed to have some type of disorder treated by orphan drugs.) “Markets of a few hundred to a

Orphan drugs will be 15.9% of worldwide prescription sales, excluding generics.

policy change,” she said. Some modifications of policy should be expected, however. “Previously, many orphan conditions did not have any drug treatments available, and it was highly unlikely that a payor would exclude an orphan drug from its formulary. But now, with the evolution of multiple drugs for an orphan disease, health plans may choose a preferred therapy and push selection of a preferred agent via lower prior authorization barriers and lower out-of-pocket costs,” Ms. Lima said. “Changes to current payor policies in the next several years are likely to include greater scrutiny of orphan oncology products, changes at the site of care and mandated specialty pharmacy use.”

‘Changes to current payor policies in the next several years are likely to include greater scrutiny of orphan oncology products, changes at the site of care and mandated specialty pharmacy use.’ —Hetty Lima, PharmD few thousand patients are completely different from larger markets of 50,000 to 200,000, and they require a completely different clinical approach,” he said.

Payors Seem Willing To Pay Surprisingly, payors don’t appear to be likely to tighten their belts on orphan drugs in the near future. Ms. Lima cited a Leerink survey of 34 payors covering more than 90 million lives in the United States, who said their coverage or access policies were largely unlikely to change over the next several years. “There was only a 17% chance that policies on orphan drugs would tighten in 2016, and even by 2020, only a 35% probability of

When it comes to orphan and ultraorphan diseases, said Sarah Marche, vice president of pharmacy markets at Highmark, in Pittsburgh, it’s particularly important for employers who are paying for coverage to be educated. “We get the question: Should we just not pay for these? And we say no, that’s not really the answer. The typical levers like utilization management don’t work—these drugs aren’t used off-label. We have to educate the employers to understand why we have to pay for them, why they add value, and to have a comfort level that they’re being used in the right population.” —Gina Shaw

Trusted to take a bite out * of G-CSF acquisition costs GRANIX X® has gained >3 34% share of the t US short-actting G-CSF hospita al marrket in its first 17 monthss1 » A 71% red duction in duration of severe e neutrropenia vs placebo (1.1 days vs 3.8 days, p<0.000 01)2 – Efficacy was evaluated in a mu ultinattional, m multi ltice t center, random mizzed e , co c ntrolllled ed d, Ph P a asse IIIII st stu udy of che h mo moth th her erap apyap y-na naïv ïve e pati patien ents ts V bo olu us))/d /doc occet etax axel ax el (75 mg/ g/m m2)2 with high h-risk breast cancer re eceivin ng doxo orubicin n (60 mg/m2 IV » The safetyy of GRANIX was esttab blish hed in 3 Ph Phasse II III trria alss, wi with th 680 80 pat atie ie ent ntss re recce ceivin ceiv ivving g ch hem emo othera othe rapy py for eithe herr br breast cancer,, lung cance er, or non-Hodgkin lyym mpho oma ma (NH NH HL)2 » Offering a prese entatio i n fo for se elf--a adm dmin nisstr trat atio at io on

Indication » GRAN GRANIX X is a le eukkoc o yt yte e gr grow owth ow th fa acto ac t r indi to d ca cate ted te d fo forr re redu duct ctio ion n in the durat atio ion of severe neutropeniia in patients with nonmyeloid malilign ma g a gn an nci c es es rec ecei eivi ei ving vi ng mye yelo losu lo supp pre r sssive an anti tica canc ncer er dru rugs gs ass ssoc o ia ated with a clinically significant incidence of febrile neutropenia.

Important Safety Information » Sp Sple leni le nicc ru ni upt ptur ure: ur e: Spl e: p en e ic rup uptu turre e, in incl clu udin ng fatal ca c ses, can occur following the administration of human granulocyte colonystim st imul im ulat ul atin at ing in g fa fact c or ct o s (h ( GG-CS CSFs Fs). ). Dis isco ont ntinue GRANIX and evaluate for an enlarged spleen or splen nic rupture in patients who repo re port po rt upp pper abd b om omin inal al or sh s ou ould der pain a after receiving GRANIX. » Ac Acut ute ut e re resp spiirrat sp ator orry di dist stre ress ss syn y drom me (A ARDS): ARDS can occur in patients receiving hG-CSFs. Evaluate patients who develop fever and an d lu lung ng g inf n ililtr trat ates es or re resp spir irat atory distresss after receiving GRANIX, for ARDS. Discontinue GRANIX in n patients with ARDS. » Al Alle lerg le rgic ic react eactio ionss: Ser eriouss allerrgic reactions, including anaphylaxis, can occur in patients receivving hG-CSFs. Reactions can occu oc cu ur on ini niti tial al exp xpos o urre. Perrma anently discontinue GRANIX in patients with serious allergic reacctions. Do not administer GRAN GR ANIX IX to pa pati tien ents t wit ith h a hi h st sto oryy of se erious allergic reactions to filgrastim or pegfilgrastim. » Us U e in pattie ient ntss wi with th sickl kle ce c ll diseasse: Severe and sometimes fatal sickle cell crises can occurr in patients with sickle cellll dis ce isea easse s rec ecei eivi ving n hG-CSFs F . Consid der the p potential risks and benefits prior p to the administrattion of GRANIX in patients with sick si ckle le cel elll di dise seas ase. e Dissco c ntinue GRANIX X in patients undergoing a sickle cell crisis. » Capi Capilllar ary y le leak ak syndr d ome (CLS):: CLS ca an occur in patients receiving hG-CSFs and is characte erize ed by hypotension, hypo hy poal albu b mi m ne emi mia, ede ema and h hemoco oncentration. Episodes vary in frequency, severity and may be life-threatening if treatment is del elay ayed ed d. Pati t ents who develo op symp ptoms of CLS should be closely monitored and receive sta andard symptomatic treatmen e t, whic wh ich h ma mayy includ de a need for in ntensive e care. » Pote Po ent ntia al for tumor growth stim mulatory effects on malignant cells: The granulocyte colony-stim mulating factor (G-CSF) receptor, thro th roug gh wh which GR RANIX X acts, hass been found f on tumor cell lines. The possibility that GRANIX act c s as a growth factorr for any tumor type ty p , in nclu u uding myeloi myeloid o d maligna ancies and myelodysplasia, diseases for which GRANIX is not apprroved, cannot be excluded. »M Most s com mmon treatment-emergent adverse reaction: The most common treatment-emergent adverse reaction that occurred in n pattientss treated wi w th GRANIX X at the e recommended dose with an incidence of at least 1% or greater and tw wo times more freq fr e ue ent n than in the placebo gro oup wa as bone pain. Plea Pl e se e see e brief summary of Fulll Prescribing Information on adjacent page.

For more information, visit GRANIXhcp.com. *Ba Base sed d on o who ole lesa ale e acquisiition n cost (WA AC) of all short-acting G-CSF products as of March 2015. WAC represents pub blished catalogue or list prices and mayy no ma nott re repr pre e en es nt actual tra ans nsactional p prices. Ple ease contact your supplier for actual prices. ease prices R fe Re fere renc nces es: 1. Th Thiss inf nfo orma mati tion n iss an a estim mate de derived from the use of information under license from the following IMS S Health Information Service: IMS Nati Na t on ti onal al Sal ales es Per ersp spec ecti tive ve, GR GRAN ANIX X mic i rro ogr g ams byy non-federal hospital channel March 2015. IMS expressly reserves all rights, including right h s of copying, d st di stri ribu b ti bu t on on, an nd re epu publ b ic icat atio on (m mic icro rogr gram ams ca alcul ullate ed as eaches x strrength). 2. GRANIX® (tbo-filgrastim) Inje j ction Presccribing Information. North Wales, PA A: Teva Te va Pha harm rmac a euti ac eutica cals ls;; 20 2014 14..

©2015 ©201 5 Ce Ceph phal alon on,, In Inc. c , a wh w olllyy-o -owned e sub u sidiary of Teva Pharmaceutical Industries Ltd. GRANIX is a registered t ad tr adem emar arkk of Tev eva a Ph Phar arma m ce ceut utic iccal a Ind ndustrries Ltd. All rights reserved. GRX-40681 May 2015.

Specialty Pharmacy Continuum • June/July 2015

CLINICAL

RA continued from page 13

patients who have comorbid conditions. RA patients are approximately twice as likely to be diagnosed with heart failure as non-RA individuals.15 Lung disease, depression, and anemia are also more prevalent in the RA population.15 Whether it is counseling about proper administration technique or notifying the prescriber about a new side effect, these interventions are essential for improving patients’ quality of

life by managing their disease and therapy. Walgreens Specialty Pharmacy offers education on specialty disease states and medications in the form of pharmacist counseling and educational material, including Wellness Planners, which are disease-specific educational booklets.

Conclusion The continual interaction between the patient and the specialty pharmacy is fundamental in the continuity of care for RA patients. Specialty pharmacists

can improve the quality of life for these patients by providing expert advice and support of treatment regimens and disease states, as well as encouraging medication adherence.

References 1. Centers for Disease Control and Prevention. National and state medical expenditures and lost earnings attributable to arthritis and other rheumatic conditions—United States, 2003. MMWR Morb Mortal Wkly Rep. 2007;56(1):4-7. 2. Centers for Disease Control and Prevention. Rheumatoid arthritis. www.cdc.gov/arthritis/ basics/rheumatoid.htm. Accessed May 11, 2015.

3. Tymms K, Zochling J, Scott J, et al. Barriers to optimal disease control for rheumatoid arthritis patients with moderate and high disease activity. Arthritis Care Res. 2014;66(2):190-196. 4. Tkacz J, Ellis LA, Myer R, et al. Quality process measures for rheumatoid arthritis: performance from members enrolled in a national health plan. J Manag Care Spec Pharm. 2015;21(2):135-143. 5. American College of Rheumatology. Rheumatoid arthritis. www.rheumatology. org/Practice/Clinical/Patients/Diseases_ And_Conditions/Rheumatoid_Arthritis/. Accessed May 11, 2015. 6. Arthritis Foundation. Rheumatoid arthritis symptoms. www.arthritis.org/about-arthritis/ types/rheumatoid-arthritis/symptoms.php. Accessed May 11, 2015. 7.

BRIEF SUMMARY OF PRESCRIBING INFORMATION FOR GRANIX® (tbo-filgrastim) injection, for subcutaneous use SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE GRANIX is indicated to reduce the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. 4 CONTRAINDICATIONS None. 5 WARNINGS AND PRECAUTIONS 5.1 Splenic Rupture Splenic rupture, including fatal cases, can occur following administration of human granulocyte colony-stimulating factors. In patients who report upper abdominal or shoulder pain after receiving GRANIX, discontinue GRANIX and evaluate for an enlarged spleen or splenic rupture. 5.2 Acute Respiratory Distress Syndrome (ARDS) Acute respiratory distress syndrome (ARDS) can occur in patients receiving human granulocyte colony-stimulating factors. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients with ARDS. 5.3 Allergic Reactions Serious allergic reactions including anaphylaxis can occur in patients receiving human granulocyte colony-stimulating factors. Reactions can occur on initial exposure. The administration of antihistamines‚ steroids‚ bronchodilators‚ and/or epinephrine may reduce the severity of the reactions. Permanently discontinue GRANIX in patients with serious allergic reactions. Do not administer GRANIX to patients with a history of serious allergic reactions to filgrastim or pegfilgrastim. 5.4 Use in Patients with Sickle Cell Disease Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disease receiving human granulocyte colony-stimulating factors. Consider the potential risks and benefits prior to the administration of human granulocyte colony-stimulating factors in patients with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis. 5.5 Capillary Leak Syndrome Capillary leak syndrome (CLS) can occur in patients receiving human granulocyte colonystimulating factors and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care. 5.6 Potential for Tumor Growth Stimulatory Effects on Malignant Cells The granulocyte colony-stimulating factor (G-CSF) receptor through which GRANIX acts has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which GRANIX is not approved, cannot be excluded. 6 ADVERSE REACTIONS The following potential serious adverse reactions are discussed in greater detail in other sections of the labeling: UÊ -« i VÊ,Õ«ÌÕÀiÊQsee Warnings and Precautions (5.1)] UÊ VÕÌiÊ,iÃ« À>Ì ÀÞÊ ÃÌÀiÃÃÊ-Þ `À iÊQsee Warnings and Precautions (5.2)] UÊ -iÀ ÕÃÊ iÀ} VÊ,i>VÌ ÃÊQsee Warnings and Precautions (5.3)] UÊ 1ÃiÊ Ê*>Ì i ÌÃÊÜ Ì Ê- V iÊ i Ê Ãi>ÃiÊQsee Warnings and Precautions (5.4)] UÊ >« >ÀÞÊ i> Ê-Þ `À iÊ[see Warnings and Precautions (5.5)] UÊ * Ìi Ì > Êv ÀÊ/Õ ÀÊ À ÜÌ Ê-Ì Õ >Ì ÀÞÊ vviVÌÃÊ Ê > } > ÌÊ i ÃÊQsee Warnings and Precautions (5.6)] The most common treatment-emergent adverse reaction that occurred at an incidence of at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group was bone pain. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. GRANIX clinical trials safety data are based upon the results of three randomized clinical trials in patients receiving myeloablative chemotherapy for breast cancer (N=348), lung cancer (N=240) and non-Hodgkin’s lymphoma (N=92). In the breast cancer study, 99% of patients were female, the median age was 50 years, and 86% of patients were Caucasian. In the lung cancer study, 80% of patients were male, the median age was 58 years, and 95% of patients were Caucasian. In the non-Hodgkin’s lymphoma study, 52% of patients were male, the median age was 55 years, and 88% of patients were Caucasian. In all three studies a placebo (Cycle 1 of the breast cancer study only) or a non-US-approved filgrastim product were used as controls. Both GRANIX and the non-US-approved filgrastim product were administered at 5 mcg/kg subcutaneously once daily beginning one day after chemotherapy for at least five days and continued to a maximum of 14 days or until an ANC of *10,000 x 106/L after nadir was reached.

Bone pain was the most frequent treatment-emergent adverse reaction that occurred in at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group. The overall incidence of bone pain in Cycle 1 of treatment was 3.4% (3.4% GRANIX, 1.4% placebo, 7.5% non-USapproved filgrastim product). Leukocytosis In clinical studies, leukocytosis (WBC counts > 100,000 x 106/L) was observed in less than 1% patients with non-myeloid malignancies receiving GRANIX. No complications attributable to leukocytosis were reported in clinical studies. Additional Adverse Reactions Other adverse reactions known to occur following administration of human granulocyte colony-stimulating factors include myalgia, headache, vomiting, Sweet’s syndrome (acute febrile neutrophilic dermatosis), cutaneous vasculitis and thrombocytopenia. 6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The incidence of antibody development in patients receiving GRANIX has not been adequately determined. 7 DRUG INTERACTIONS No formal drug interaction studies between GRANIX and other drugs have been performed. Drugs which may potentiate the release of neutrophils‚ such as lithium‚ should be used with caution. Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C Risk Summary There are no adequate and well-controlled studies of GRANIX in pregnant women. In animal reproduction studies, treatment of pregnant rabbits with tbo-filgrastim resulted in increased spontaneous abortion and fetal malformations at systemic exposures substantially higher than the human exposure. GRANIX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal Data In an embryofetal developmental study, pregnant rabbits were administered subcutaneous doses of tbo-filgrastim during the period of organogenesis at 1, 10 and 100 mcg/kg/day. Increased abortions were evident in rabbits treated with tbo-filgrastim at 100 mcg/kg/day. This dose was maternally toxic as demonstrated by reduced body weight. Other embryofetal findings at this dose level consisted of post-implantation loss‚ decrease in mean live litter size and fetal weight, and fetal malformations such as malformed hindlimbs and cleft palate. The dose of 100 mcg/kg/day corresponds to a systemic exposure (AUC) of approximately 50-90 times the exposures observed in patients treated with the clinical tbo-filgrastim dose of 5 mcg/kg/day. 8.3 Nursing Mothers It is not known whether tbo-filgrastim is secreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when GRANIX is administered to a nursing woman. Other recombinant G-CSF products are poorly secreted in breast milk and G-CSF is not orally absorbed by neonates. 8.4 Pediatric Use The safety and effectiveness of GRANIX in pediatric patients have not been established. 8.5 Geriatric Use Among 677 cancer patients enrolled in clinical trials of GRANIX, a total of 111 patients were 65 years of age and older. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients. 8.6 Renal Impairment The safety and efficacy of GRANIX have not been studied in patients with moderate or severe renal impairment. No dose adjustment is recommended for patients with mild renal impairment. 8.7 Hepatic Impairment The safety and efficacy of GRANIX have not been studied in patients with hepatic impairment. 10 OVERDOSAGE No case of overdose has been reported. ©2014 Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical Industries Ltd. All rights reserved. GRANIX is a registered trademark of Teva Pharmaceutical Industries Ltd. Manufactured by: Distributed by: Sicor Biotech UAB Teva Pharmaceuticals USA, Inc. Vilnius, Lithuania North Wales, PA 19454 U.S. License No. 1803 Product of Israel GRX-40581 January 2015 This brief summary is based on TBO-004 GRANIX full Prescribing Information.

Cojocaru M, Cojocaru IM, Silosi I, et al. Extraarticular manifestations in rheumatoid arthritis. Maedica (buchar). 2010;5(4):286-291.

8. Jung OY, Kim HA. Recent paradigm shifts in the diagnosis and treatment of rheumatoid arthritis. Korean J Intern Med. 2012;27(4):378-387. 9. Singh JA, Furst DE, Bharat A, et al. 2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res. 2012;64(5):625-639. 10. Kahlenberg JM, Fox DA. Advances in the medical treatment of rheumatoid arthritis. Hand Clin. 2011;27(1):11-20. 11. Breedveld FC, Weisman MH, Kavanaugh AF, et al. The PREMIER study: a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006;54(1):26-37. 12. Giezen TJ, Mantel-Teeuwisse AK, Straus SM, et al. Safety-related regulatory actions for biologics approved in the United States and the European Union. JAMA. 2008;300(16):1887-1896. 13. Xeljanz [package insert]. New York, NY: Pfizer Laboratories; 2014. 14. Joplin S, Van der Zwan R, Joshua F, et al. Medication adherence in patients with rheumatoid arthritis: the effect of patient education, health literacy, and musculoskeletal ultrasound. Biomed Research International. 2015; Article ID 150658. 15. Gabriel SE, Michaud K. Epidemiological studies in incidence, prevalence, mortality and comorbidity of the rheumatic diseases. Arthritis Res Ther. 2009;11:229.

Next Issue: Spotlight on MS

on’t miss our next autoimmunefocused spotlight, focusing on multiple sclerosis. Although there is no cure for MS, there are a number of treatments available that can slow disease progression or modify its course. This spotlight will highlight the new approaches to treatment and management of this chronic and progressive autoimmune disorder.

Specialty Pharmacy Continuum • June/July 2015

CLINICAL

continued from page 1

as in the entire previous 50-year period between 1953 and 2003, Mr. Ellis noted. “And 35% of the oncology agents now in clinical trials are oral agents.” At first glance, this may seem to portend easier courses of therapy. The oral agents do allow for more flexibility and convenience, but Mr. Ellis explained that there are other complicating factors that will likely require more—not less—skilled management from specialty pharmacy: • Patients on oral therapies might decide to modify their own drug regimen dosing, potentially leading to ineffective or wasted treatment. • Oral therapies have adherence and compliance issues on par with general medications. • The oral route does not necessarily mean a better safety profile. • Accessing oral therapies can be more difficult for providers because of prior authorizations and limited access. • Physicians often prefer in-office therapies to better manage care. There is also the increasing cost of that care. Rowena Schwartz, PharmD, BCOP, vice president of clinical content and pharmacy operations for McKesson Specialty Health, in Houston, pointed to a 2011 study projecting a 27% increase in the cost of cancer care by 2020 ((J Natl Cancer Inst 2011;103[2]:117-128). Four years later, those numbers have already been blown out of the water, she noted. For example, The State of Cancer Care in America: 2014, a report released last year by the American Society of Clinical Oncology, projects that the total cost of U.S. cancer care will reach $175 billion by 2020—a 40% increase over 2010. “We’re already on pace to far exceed earlier projections, so when we estimate costs for 10 years out, it’s impossible to get a handle on what these expenditures will look like,” based on the rapid-fire progress in cancer therapy, Dr. Schwartz said. “Last year alone, there were 10 new cancer treatments available. I remember when we got one new drug every three years and thought that was great. Now, there are more and more first-in-class drugs, and the challenge of how we put them into treatment is constantly changing.” She cited, as an example, the rapid pace of approvals for new indications. “Within two months after approval, a drug gets a new indication for a totally different disease,” Dr. Schwartz said. “These agents are evolving in how they’re used and we need to stay ahead of them, to ensure patients get the benefits but the system isn’t overwhelmed in terms of cost.” One area where oncology pharmacists can play a key role, she noted, is in the development, adoption and implementa-

tion of new clinical pathways that identify cost-effective and evidence-based therapies, not just for direct drug therapy but for supportive treatments as well. Dr. Schwartz cited several recent studies showing that clinical pathways have decreased the cost of care in oncology with no negative effect on outcomes. For example, a 2010 study that looked at the 12-month cost of treatment for non-small cell lung cancer found that the cumulative cost for off-pathway patients was nearly $28,000, compared with just over $18,000 for on-pathway

therapy got these factors; on the other hand, 96% of CSFs were administered in settings where they were not recommended,” she reported. “Cancer care in many cases remains very fragmented, with patients moving from one doctor to another to another in a way that’s not coordinated, from the diagnostic component, then to treatment mode, then to maintenance mode,” she said. “I’m hearing a lot of desire to put together more comprehensive cancer management in a way that the patient stays in the middle, rather than the physician.”

Most valuable services (top 4+5)

100

Services provided by SPP

from speciialty pharmaacies. That’’s a big challlenge for our industry, stays ing on top p of the thingss payors and patients care about and reporting the information back.” The oncology prescription channel continues to shift, Mr. Ellis added. “You see places like CVS, Rite-Aid, the Apothecary Shop and others starting

Satisfaction with services (top 4+5)

91 83

Health Plans, %

ORAL CHEMO

74 66 66

60 52

50 23 44

40 23

20 0 Ensure appropriate dose of medication

Manage drug waste, abuse and misuse

Implement adherence and persistence programs

Manage adverse events

Provide adherence performance guarantees

Coordinate hospital discharge medication reconciliation

Figure. Specialty pharmacy provider clinical utilization and management services. SPP, specialty pharmacy providers

patients—with no difference in overall survival ((J Oncol Practt 2010;6[1]:12-18). “There are plentiful guidelines, such as those from NCCN [National Comprehensive Cancer Network] and ASCO [American Society of Clinical Oncology], to help you understand the literature, but there’s so much data now that it really helps for practitioners to take those guidelines and make them usable as pathways for the front-line clinician,” she told Specialty Pharmacy Continuum.

Key Roles for SP Providers Large gaps in the adoption of such pathways, and in the coordination of cancer care, also suggest key roles for the specialty pharmacist and the data and benchmarking they can offer, said Debbie Stern, RPh, a senior vice president for strategy and business development for medical oncology and specialty drugs at CareCore/MedSolutions, a specialty benefits management firm headquartered in Bluffton, S.C. Ms. Stern illustrated those gaps with a telling study ((J Natl Cancer Inst 2011;103[12]:979-982) on the use of colony-stimulating factors (CSFs) in lung and colorectal cancer patients. The study found that patients were both over- and undertreated with CSFs. “Only 17% of patients undergoing high-risk chemo-

But payors remain insufficiently aware of what many specialty pharmacies can do, and are doing, to reduce that fragmentation, coordinate care and reduce costs, Ms. Stern said. In this year’s 11th edition of the EMD Serono Specialty Digest, released in May, she noted, payors ranked ensuring the appropriate dose of medication; managing drug waste, abuse and misuse; and implementing adherence and persistence programs as the most valuable services they sought from a specialty pharmacy (Figure). But the gap between the importance of those services and how satisfied they were with their specialty pharmacy’s services in those areas was significant—91% vs. 60%, 83% vs. 51%, and 71% vs. 52%, respectively. “There’s really a disconnect here,” Ms. Stern said. “So many specialty pharmacies provide great services, and so many payors do not recognize this. I implore you to get out and share some of this information with clients. Ask them basic questions, like ‘Do you know we do this? Are you satisfied with our services? How would you benchmark us?’”

to transition from the prescriptions in the clinic, to the outpatient setting, to recently more and more local specialty pharmacies cropping up with access to these drugs.” Specialty pharmacies are well positioned to create additional value in the oncology marketplace, Mr. Ellis said. “As payors continue to shift away from traditional fee-for-service models, utilization of services will be essential. Pharmacists are taking on a new role in medical home models and shared savings, and we need to leverage the national footprint of pharmacists to provide a high level of care outside the clinical setting.” One option is for limited distribution drugs to be distributed selectively at local specialty pharmacies. “Local specialty pharmacies can partner with oncology clinics,” he said. “We’re seeing more and more access being granted, but the challenge will be to manage side effects and [Risk Evaluation and Mitigation Strategies] programs on a real-time basis.” —Gina Shaw

Payors Ask, Where Are Data? Mr. Ellis said that, in his meetings with payors, the chief complaint is lack of data. “One of their big complaints is that they rarely get actionable information back

Dr. Schwartz is employed by McKesson Specialty Health and is a stockholder. Mr. Ellis is employed by Walgreens. Ms. Stern reported no relevant ﬁnancial conﬂicts of interest.

Specialty Pharmacy Continuum • June/July 2015

CLINICAL

Report From ASCO Annual Meeting:

Combo Rx Offers Beneﬁt in Metastatic Melanoma Chicago—In previously untreated patients with metastatic melanoma, the combination of ipilimumab and nivolumab provided a nearly 60% increase in progression-free survival (PFS) relative to ipilimumab alone. Drawn from a Phase III trial called CheckMate 067, the data were characterized as setting a new treatment standard. “Based on the results of nivolumab alone and nivolumab plus ipilimumab arms relative to ipilimumab and the prior study comparing pembrolizumab to ipilimumab, it is my opinion that ipilimumab alone can no longer be considered a standard first-line immunotherapy for patients with advanced melanoma,” asserted Michael B. Atkins, MD, the deputy director of Georgetown University’s Lombardi Comprehensive Cancer Center, in Washington, D.C., who was the invited discussant for this trial at the 2015 annual meeting of the American Society of Clinical Oncology (ASCO), where the data were presented during the plenary session (abstract LBA1). The study, which was published simultaneously in The New England Journal of Medicine (May 31. [Epub ahead of print]), was supported by Bristol-Myers Squibb. In this trial, presented by Jedd D. Wolchok, MD, the chief of the Melanoma and Immunotherapeutics Service at Memorial Sloan-Kettering Cancer Center, in New York City, 945 previously untreated patients with unresectable stage III or IV melanoma were randomized to the CTLA-4 checkpoint inhibitor ipilimumab (Yervoy, Bristol-Myers Squibb) alone, the PD-1 checkpoint inhibitor nivolumab (Opdivo, Bristol-Myers Squibb) alone, or a combination of the two. Both medications have indications for melanoma, but they had not been evaluated in combination in a Phase III trial. After a median follow-up of slightly

more than a year, the PFS rates were 2.9 months with ipilimumab alone, 6.9 months with nivolumab alone and 11.5 months with the combination. These translated into favorable hazard ratios (HR) for the combination relative to ipi-

group but 14 months in both the combination group and the nivolumab-alone group. In patients with tumors with less than 5% PD-L1 expression, the median PFS was 2.8 months with ipilimumab alone, 5.3 months with nivolumab alone and 11.2 months with the combination. Investigator-assessed objective response rates (57.6%) and complete response rates (11.5%) were higher with the combination treatment relative to nivolumab alone (43.7% and 8.9%) and ipilimumab alone (19% and 2.2%). Higher objective response rates were observed in patients with tumors expressing greater

limumab alone (0.42; P<0.001) and for nivolumab alone relative to ipilimumab alone (0.57; P<0.001). The combination showed a numerical advantage over nivolumab alone in an exploratory analysis (HR, 0.74; significance not assessed). The PFS advantage of the combination treatment over ipilimumab alone was consistent across a large number of subgroups, including BRAF mutation status and PD-L1 expression. However, greater than 5% PD-L1 expression was a factor in relative PFS rates. In patients whose tumors had greater than 5% PD-L1 expression, the median PFS was 3.9 months in the ipilimumab alone

than 5% PD-L1 relative to those expressing less than 5% PD-L1, particularly with the combination (72.1% vs. 54.8%) and nivolumab alone (57.5% vs. 41.3%). In patients randomized to ipilimumab alone, the difference in objective response rates between those with tumors expressing greater than 5% PD-L1 and those with tumors expressing less than 5% PD-L1 was narrower (21.3% vs. 17.8%). The combination was less well tolerated than either immunotherapy alone. Discontinuations due to adverse events (AEs) occurred in 36.4% of patients in the combination arm versus 7.7% of those receiving nivolumab alone and 14.8% of

those receiving ipilimumab alone. The grade 3 or higher AEs that occurred more commonly with the combination relative to nivolumab alone and ipilimumab alone, respectively, included diarrhea (9.3% vs. 2.2% and 6.1%), rash (4.8% vs. 0.6% and 1.9%), fatigue (4.2% vs. 1.3% and 1.0%), vomiting (2.6% vs. 0.3% and 0.3%) and liver enzyme abnormalities (6.1% vs. 1.0% and 0.6%). However, immune-modulatory agents— used in nearly half of patients receiving nivolumab alone, more than half of those receiving ipilimumab alone and nearly 85% of those receiving both agents— were effective in modifying the intensity of these AEs, according to Dr. Wolchok. Overall survival data from this trial are pending, but, as noted by Dr. Atkins, the data are already sufficiently compelling to suggest a new standard of care. According to Dr. Atkins, more work needs to be done on biomarkers to predict response and to explore whether alternative ipilimumab schedules or substitution of other immunotherapies for ipilimumab could improve the therapeutic effectiveness of this combination. However, he considered these results to be “the latest in a series of breakthroughs” that have dramatically changed the prognosis of a cancer for which the median survival just five years ago was six to nine months. —Ted Bosworth Dr. Wolchuk reported financial relationships with Bristol-Myers Squibb, EMD Serono, GlaxoSmithKline, Janssen, Jounce Therapeutics, Medimmune, Merck, Polaris, Polynoma Potenza Therapeutics, Vesuvius and Ziopharm Oncology. Dr. Atkins reported financial relationships with Alkermes, Amgen, Bristol-Myers Squibb, C-Cam, Costim, Genentech, GlaxoSmithKline, Infinity, Lilly, Merck, Neostem, Novartis, Pfizer and X4.

Breakthrough Treatment for Multiple Myeloma Nears Chicago—Roughly a year after the immunotherapy agent elotuzumab (Bristol-Myers Squibb/AbbVie) received breakthrough therapy designation from the FDA, the drug is poised to change the treatment landscape of multiple myeloma. At the annual meeting of the American Society of Clinical Oncology, researchers from the ELOQUENT-2 trial reported that adding elotuzumab to dexamethasone and lenalidomide (Revlimid, Celgene) improved median progressionfree survival (PFS) by four months in patients with relapsed/refractory mul-

tiple myeloma (abstract 8508). “Based on this randomized Phase III trial, we hope that we will soon have a new treatment option,” said lead author Sagar Lonial, MD, a professor and the executive vice chair in the Department of Hematology and Medical Oncology, and a professor and chief medical offi-

cer at the Winship Cancer Institute of Emory University, in Atlanta. Elotuzumab is a novel immunostimulatory monoclonal antibody with a dual mechanism of action that targets both the tumor cell and immune-mediated natural killer cells. ELOQUENT-2 randomized patients with relapsed/refractory multiple myeloma who had received one to three prior lines of therapy to receive lenalidomide/dexamethasone (n=325) alone or with elotuzumab (n=321). Prior lenalidomide exposure was allowed in 10% of the study population. All patients

received premedication to mitigate infusion reactions before elotuzumab administration. Roughly one-third of patients had a deletion 17p mutation and 10% had a t(4;14) translocation; these characteristics are associated with a poor prognosis. Roughly half of the study population had received a stem cell transplant, and onethird were refractory to their most recent line of therapy. Patients had received a median of two prior lines of therapy. Patients receiving elotuzumab had a significantly improved PFS (median 19.4 vs. 14.9 months; hazard ratio, 0.70;

Specialty Pharmacy Continuum • June/July 2015

CLINICAL

P=0.0004). The overall response rate was higher in the elotuzumab arm (70% vs. 66%; P=0.0002). The benefit of elotuzumab was consistent across key subgroups, including high-risk patients and elderly patients. Dr. Lonial noted that the difference between the elotuzumab and control groups appeared to become more pronounced over time. Separation of the curves and the maintenance of benefit over time have been observed with other immunologic approaches.

Nearly Equivalent AEs Patients receiving elotuzumab had higher rates of all grades of infection (81% vs. 28%) as well as grade 3/4 infection (74% vs. 24%), but Dr. Lonial pointed out that if adjustment is made in the incidence of infectious complications for the duration of therapy, the absolute incidence per year of exposure is the same. Based on such an analysis, he noted, “The incidence of toxicity across the board is relatively similar between the two arms.” Infusion reactions occurred in 10% of elotuzumab patients (no grade 4/5 infusion reactions.) Only 1% of patients withdrew from the study due to an infusion reaction. Elotuzumab did not adversely affect overall health-related quality of life. Jeffrey Wolf, MD, the director of the Muliple Myeloma Program at the Helen Diller Family Comprehensive Cancer Center at the University of CaliforniaSan Francisco, said the ELOQUENT-2 data showing improved PFS are encouraging, and suggest that elotuzumab “may have a role in extended control of disease after initial response.”

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Dr. Wolf pointed out that there is a tail on the PFS curve for patients receiving elotuzumab, “implying a cohort of patients [that achieved] an extended benefit.” Elotuzumab thus may prove to be “a good candidate for maintenance therapy.” He also stressed that “there is very little additional toxicity with the addition of elotuzumab, making it an easy drug to add to other combinations.” Dr. Wolf added that “it will be interesting to see how elotuzumab fares against the coming anti-CD38 antibodies” being

tested in clinical trials for myeloma, including daratumumab (Genmab). ELOQUENT-2 results have been published in The New England Journal of Medicine (2015 Jun 2. [Epub ahead of print]). —Kate O’Rourke Dr. Lonial disclosed consultancy fees and research funding from Bristol-Myers Squibb, Celgene, Janssen, Millennium, Novartis and Onyx. Dr. Wolf disclosed stock ownership in Celgene; a consulting/advisory role with Amgen, Celgene, Janssen and Onyx; and being on the speakers bureau of Millennium.

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Specialty Pharmacy Continuum • June/July 2015

CLINICAL

Individualized Approach Drives Success in CIDP In patients with severe chronic inflammatory demyelinating polyneuropathy (CIDP), there is evidence that intravenous immune globulin (IVIG) therapy is superior to corticosteroids as a first-line strategy. However, this is not a general statement applicable to all patients with CIDP, particularly on a costbenefit basis, according to published reviews, and experts questioned the best management. Essentially, all advocated an individualized approach. “IVIG was always considered the second-line option, but it is increasingly being employed first-line in selected patients. Relative to steroids, the response is faster and it is typically better tolerated,” reported Jerry Siegel, PharmD, a clinical associate professor at the Ohio State College of Pharmacy, in Columbus. However, just as the presentation of CIDP is heterogeneous, so should be the treatment. According to Dr. Siegel and others, therapy should be individualized and adjusted at appropriate intervals. “CIDP is not curable; it is just controllable. Most patients will require therapy at least periodically for the rest of their

lives,” Dr. Siegel explained. The chronicity of CIDP creates manyy of the challenges. Steroids are effective but bring a long list of significant adverse events, particularly over extended use. Although better tolerated, IVIG imposes a high cost that can be particularly onerous when it is provided as a maintenance regimen over an indefinite period. Moreover, IVIG has its own potential for adverse events, including an increased risk for thromboembolism. Less frequently used therapies, such as mycophenolate, cyclosporine and azathioprine, are generally reserved for patients who fail first-line treatments.

Plasma exchange is also considered among front-line therapies, but this treatment, which requires multiple treatment sessions to provide benefit, is associated with a higher rate of relapse than the other two options ((Adv Neurol Disord 2011;4:193-200). As a result, the recent debate over the optimal first-line choice has usually focused on the merits of IVIG compared with corticosteroids. If cost was eliminated as a factor, IVIG would be likely to win on the basis of tolerability if not efficacy. Although some patients develop allergic reactions or

unacceptable side effects, such as headache or nausea, IVIG carries a lower burden of risks than steroids, which can produce a broad range of systemic adverse events, including weight gain, impaired bone metabolism, fat deposits and increased susceptibility to infection. The risk for many of these adverse events increases with treatment duration. “IVIG, in view of the latest trial data, represents a more justified first choice if function is severely impaired, because it offers a higher likelihood of side effect– free therapeutic response in the short

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CLINICAL

term,” said Yusuf A. Rajabally, MD, a consultant neurologist at Regional Neuromuscular Clinic, Queen Elizabeth Neurosciences Center, at the University of Birmingham, in the United Kingdom. However, in a recent review attempting to sort out when to consider IVIG over steroids in CIDP, Dr. Rajabally hesitated to advocate IVIG as a uniform first-line standard ((Muscle Nerve 2015;51:657-661). Like Dr. Siegel, Dr. Rajabally pointed out that IVIG is not without risks, particularly the risk for thromboembolism that may make it an unattractive choice for patients who have an increased risk for clotting. In addition, Dr. Rajabally suggested that steroids might be a better initial choice in mild disease when withdrawal of therapy after a limited course is anticipated. He cited evidence that remissions achieved on steroids are more durable ((J Neurol Neurosurg Psychiatryy 2014;85:901-906). Despite several published studies, it is unclear whether IVIG is more effective than corticosteroids for initial control of CIDP, according to Dr. Rajabally. He observed that most of the comparisons have concluded that the therapies are equivalent. The one exception, a multicenter, randomized, double-blind trial, found that IVIG was less likely to be discontinued at six months due to intolerance, lack of efficacy or side effects ((Lancet Neuroll 2012;11:493-502). However, relapse rates were higher after discontinuation of IVIG than after discontinuation of steroids. Citing the more recently published extension of that double-blind study, which followed patients for a median of 42 additional months, Dr. Rajabally said the proportion of patients with a return of symptoms was similar, but the median time to deterioration after discontinuing therapy was 4.5 months in the IVIG group versus 14 months in the group initially randomized to steroids ((J Neurol Neurosurg Psychiatry 2014; Sept 22. [Epub ahead of print]). “In cases with relatively mild functional disability and without contraindications, corticosteroids may need to be considered as first-line, given the possible greater chance of future relapse-free treatment withdrawal or a longer period of remission,” Dr. Rajabally advised in his review article. For cases in which IVIG is a more attractive choice, cost remains an issue. Using relatively low doses at greater than normal dosing intervals may work for some individuals. In providing some practical advice for CIDP patients in whom good control has been achieved with the standard starting dose of 2 g/kg divided over two to five days, Dr. Siegel noted that there is no welldefined maintenance dose, which may differ among patients. “It is reasonable to reduce the dose

Cytokine production by T cells

Fc receptor expression and function on macrophages

T-cell adhesion and migration

Immune cell activation • Macrophage-T-cell interaction via costimulatory molecules • T-cell-mediated stimulation of B cells via cytokines • Antibody production by B cells

Complement activation and MAC formation

Figure. Main immunopathogenic network involved in CIDP. CIDP, chronic inflammatory demyelinating polyneuropathy; MAC, membrane attack complex; MHC, major histocompatibility complex; TCR, T-cell receptor; Source: Nat Rev Neurol. doi:10.1038/nrneurol.2011.121

in patients who are doing well. In some patients, as little as 400 mg/kg administered every three or four weeks may be sufficient for adequate control,” Dr. Siegel suggested. “If patients continue to do well, one might consider backing off the IVIG altogether to see if a remission can be sustained without drug therapy or with intermittent use of steroids.” For the same reasons, Dr. Rajabally also suggested that withdrawal of therapy, whether achieved by slow incremental weaning or a sudden halt of therapy, is justifiable. He cautioned, however, that the reduction in medication cost may be counteracted by a need for more office visits to verify sustained disease control. Drug holidays offer an opportunity to reduce drug costs while decreasing the risk for drug-related adverse events, but the chronicity of CIDP means a high likelihood of eventual relapse off therapy. CIDP has complex underlying mechanisms of action (Figure) and a variable course even with treatment. Both Drs. Siegel and Rajabally recommended objective and periodic disease assessment to consider whether dose adjustments are required. Cautioning against overtreatment with an expensive medication, Dr. Rajabally specifically recom-

mended the sequential use of functional scales that capture relative change in disability. These, he asserted, can be useful for evaluating whether patients are taking the minimally effective dose. Subcutaneous formulations of immune globulins (SQIG) are not a strategy for reducing the costs of IVIG, but some CIDP patients may prefer this route of administration, which is sometimes perceived as more convenient, according to Dr. Siegel. Most appropriate as a maintenance therapy because the IG doses are lower in most of the available SQIG products, this route of administration is often also better tolerated because it is associated with fewer peaks and troughs in plasma drug concentration, reducing the risk for dose-related adverse events. A new SQIG entry, called HyQvia (Baxter), provides IG doses equivalent to those in IVIG formulations while retaining more favorable pharmacokinetics, but this is the exception. The greatest opportunity for optimizing therapy with IVIG may await biomarkers that reveal disease activity and the effectiveness of treatments in suppressing that activity. Such biomarkers would be expected to permit more rational strategies by identifying

the minimally effective dose of any maintenance therapy, not just IVIG or steroids. However, both Drs. Siegel and Rajabally concurred that IVIG may be the most appropriate first-line choice in many CIDP patients, particularly those presenting with significant impairment and in whom continued treatment is likely to be required to maintain symptom control. —Ted Agres Dr. Siegel reported a consulting contract with Amgen, a teaching contract with Kedrion and a research contract with CSL Behring. Dr. Rajabally reported consultant fees, honoraria or other compensation from Baxter, BPL, CSL Behring, Grifols, LfB France and Octapharma.

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Specialty Pharmacy Continuum • June/July 2015

TECHNOLOGY

ArmadaOne Platform Helps Streamline Data Capture Manufacturers expect specialty pharmacies to collect data about their products and their patients, but they often want different information. Given those divergent requirements, capturing the necessary data while still meeting a patient’s clinical needs can be a challenge. To make that process less daunting, Armada Health Care has launched the ArmadaOne Specialty Pharmacy Workflow Platform, with elements tailored to each manufacturer’s products, according to Shivani Patel, PharmD, a senior director of clinical operations at Armada Health Care, Florham Park, N.J. The new software is built on the company’s existing platforms, she noted, including online therapy management, prior authorization zation and prescription referral servicees, coupled with a new specialty pharmaacy workflow component. Arpan Patel, RPh, MBA, a vice president of clinical operatio ons, said the new software was develop ped with customers’ needs in mind. Armada Health Care’s pharmacy paartners, he explained, were having troub ble juggling the care of their patieents and data collection requirements. “At the same time, the request from pharma was to have better access to the data that was flowing through those systems. So, we were trying to help thee pharmacy with workflow and a pharma with data using onee system,” he said. “The purpose of this plaatform is data reporting,” Mr. Patel added. “We have pharmacists with hin our network, whether it be our o hub program or within our GPO O [group purchasing organization] contracts, c that are not able to provide the necessary data fields back to uss or to the manufacturers, and they were w asking for assistance.”

He stressed, however, that the alerts aren’t so rigid that a patient’s access to a potentially lifesaving medication is impeded. For example, some manufacturers want to know where an organ transplant was performed when the

results of the pregnancy test, and you don’t have that information in the system, it would prevent you from moving any farther on that prescription,” he said. Such hard stops, he explained, typically happen when there is Risk Evaluation and Mitigation Strategies (or REMS) reporting involved. This system is an upgrade to existing Armada software, but it can also be used as a wrap-around for other pharmacy dispensing systems. “Whatever software you use to dispense, you would continue to use to adjudicate

‘I know from my own experience that the time and effort needed [from] employees to maintain our [home-grown] system at [a high] level was a burden on the company.’ —Nicholas Saraniti, MS

Alerts Help Streamline Tasks T Nicholas Saraniti, MS, thee owner of Solera Specialty Pharmacy in Ft. Lauderdale, Fla., a regional pharmacyy that serves primarily HIV, rheumatoid arrthritis and niche dermatology patients, worked w with the ArmadaOne product in n beta testing. He said the new softwarre’s preconfigured manufacturer-specificc data sets, which include integrated hard d and d soft f stops to ensure that data fields are filled, proved particularly useful. “As you go through the process, the software will … soft- or hard-stop you from allowing the prescription to leave your facility until the data have been collected,” Mr. Saraniti said.

company provides drug therapy for the transplant patient. The system will remind the pharmacist at various points if he or she has not yet colllected d that h d data. “But [[that’s h a soft alert]—it will not prevent the delivery of a medication,” he said. In other cases, Mr. Saraniti noted, hard stops are used to halt the dispensing process. For example, “if a medication had a pregnancy warning on it, and the data point required the

your claims,” Dr. Patel said. “You would enter your prescriptions into your pharmacy dispensing software, and through integration, the information f is pushed h d over to ArmadaONE.” The technology is embedded in the pharmacist’s workflow, she added. Mr. Saraniti uses ArmadaOne as a wraparound to the Rx 30 Pharmacy Management System by Transaction Data Systems Inc. “The integration was

relatively simple between the two products,” he said.

A Flexible System ArmadaOne can be customized to the pharmacist’s workflow, whether it is a one- or two-pharmacist practice or a large multipharmacy network, according to Dr. Patel. “Based on location, drug [and] disease state, you can configure which steps you want to work the prescription: Do you want to adjudicate the claim first with the insurance company and then talk with the patient, or do you want to talk to the patient and then adjudicate the claim?” she said. The primary features focus on hub referrals, clinical consultation, contracting with pharmaceutical p and biotech companies,, prior authorization and shipping cost management. In addition, theere is a prescriber portal to eliminaate paper prescriptions and documeents, and pharmacy and pharmaa/biotech dashboards and reportingg screens. The nottes section is robust, Dr. Patel ssaid, and includes patient nottes, order notes and clinical notes. Because the notes are n searchable and filterable, users can look through past notes for important patient information. They can also test a claim to see if insurance will pay forr it, determine what the copay is or find out if prior authorization is needed. As with h any complex software system, pharmaccies need to assess whether the build d-it or buy-it approach makes the mosst sense for a given application. Forr Mr. Saraniti, that determination, applied a to data aggregation and reportiing, was a fairly simple one to make. Beefore starting Solera in 2014, Mr. Saranitii was principal founder and CEO of Com mCare Pharmacy, a specialty pharmacy tthat he sold to Premier, the nation’s larggest GPO. He built his own system at C ComCare. “I know from my own experieence that the time and effort needed [from m] employees to maintain our system at th hat level was a burden on the company. T The reporting requirements change all tthe time. It’s not like you can build it and then leave it,” he said, adding that he prefferred handing that “burden” to Armada. d —Marie Rosenthal Shivani Patel and Arpan Patel are employees of Armada Health Care. Mr. Saraniti reported that he received no direct compensation from Armada Health Care, but was given software for the beta testing.

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TransTracker® temperature indicators give patients a clear alert as to whether their meds may have been exposed to potentially damaging temperatures. $7 saved for each $1 invested in TransTracker – A study* reported savings based on fewer unnecessary returns when TransTracker was included in every shipment.

50% reduction in call center time – When patient concerns were speciÄcally about the temperature exposure of their meds, and TransTracker was used as a decision-making tool.

95% of patients surveyed want TransTracker included in shipments – Monitoring shows specialty pharmacy concern for safety. Patients are more conÄdent and satisÄed.

Science-based temperature indicators *Request the Armada Specialty Summit video presentation From Preference to Requirement: Best Practices in Cold Chain Shipping by visiting temptimecorp.com or call 973-984-6009

VANCOMYCIN

Time-Saving Convenience

pre-weighed, pre-measured ingredients

Streamlined Process

single NDC # eases reimbursement

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KITS contain everything you need to compound individual prescriptions quickly and easily. Additional concentration and sizes available through all major distributors. To learn more about how FIRSTÂŽ KITS are transforming compounding, call

1-800-461-7449 or visit: www.CutisPharma.com