Pharmacy Practice News ( December 2020 ) by McMahon Group

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UP FRONT

Amid record COVID-19 surge, three new vaccines offer hope ....... Patient assistance programs step up during pandemic ............

POLICY

Ring in the new year with a fresh reimbursement plan ......

CLINICAL

Meeting the challenge of ambulatory ABx stewardship ...........

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Pharmacists help slow pandemic’s spread in underserved areas

Heeding the Call of COVID

even major health systems launched a new nonprofit coalition that will work to share specialty pharmacy best practices and advocate for their common interests. “We’ve seen there is a need for a platform that specifically addresses and is committed to the concerns of health systems’ specialty pharmacies,” said Tanya Menchi, the executive director of the new Health System Owned Specialty Pharmacy Alliance (HOSP). “That’s why they have come together.” Among HOSP members’ key concerns are providing patient choice of specialty pharmacy providers and accessing limited distribution and payor networks, according to Menchi. The viability and continuance of the 340B program are “obviously another big concern,” she said. Continued on page 18

OPERATIONS & MGMT

503A/503B sterile compounding not for the faint of heart.............. 17 REVIEW ARTICLE

Managing Immunotherapy Toxicities During COVID-19 See page 12.

HOSP Coalition Seeks Broader Specialty Reach

Volume 47 • Number 12 • December 2020

Multidisciplinary Team Approach Boosts Biosimilars

(Left to right): Sylvia Uong and Tina Vu, PharmD candidates at Western University of Health Sciences in Pomona, Calif., collect swabs for oropharyngeal COVID-19 PCR testing.

aiser Permanente Washington has achieved biosimilar conversion rates nearing 100%, thanks to a multidisciplinary specialty care initiative, the team reported at the American College of Clinical Pharmacy 2020 Virtual meeting. Such efforts haven’t always paid off. In 2017, a Kaiser program to convert patients from infliximab (Remicade, J&J/Janssen) to infliximab-dyyb (Inflectra, Pfizer) yielded only a 50% conversion rate. Poor patient acceptance and a belief that the switches were mandatory were the likely

are provided by pharmacists can significantly improve the prevention, screening and contact tracing of COVID-19 in underserved communities, as well as address the overall harmful effects of the pandemic on this vulnerable population, according to two studies presented at the American College of Clinical Pharmacy 2020 Virtual meeting. In the first study, clinical pharmacists went into homeless shelters in Victorville, Calif. and took steps to slow the spread of COVID-19. The pharmacy team developed policies and procedures based on the CDC’s “Interim Guidance for Homeless Service Providers” (bit.ly/ 3oYvdEo). Shelter staff were trained to follow intake and quarantine protocols assessing symptoms of COVID-19 and medical history before admitting new residents. “With higher rates of chronic diseases, homeless individuals are at increased risk for COVID-19 complications including hospitalizations and death,” said the study’s lead author, Shawn Smith, PharmD, an assistant professor of pharmacy practice and administration at Western University of Health Sciences in Pomona, Calif. “This program has provided testing to more than 100 homeless individuals and allows shelters to continue housing more than 300 individuals in the city.” Shelter staff first triage residents and homeless people at risk for exposure to COVID-19, using a standardized questionnaire on recent contacts, travel, fever, other symptoms and medical conditions. Pharmacists administered polymerase chain reaction (PCR) testing

Continued on page 16

Continued on page 6

The Year in

DRUG APPROVALS See page 20.

Up Front

Pharmacy Practice News • December 2020

COVID-19 Pandemic

Amid COVID-19 Surge, 3 Vaccines Offer Hope

y mid-November, as COVID-19 cases surged to record levels around the country, better news emerged from several key vaccine trials. Pfizer and BioNTech announced they will seek an emergency use authorization from the FDA for BNT162b2, the companies’ COVID-19 vaccine candidate. In the vaccine’s key clinical trial, BNT162b2 was 95% effective against COVID-19 beginning 28 days after a first dose; 170 confirmed cases of COVID-19 were evaluated, with 162 observed in the placebo group versus eight in the vaccine group (P<0.0001). Additionally, 10 severe cases of COVID-19 were documented in the trial, with nine of the cases occurring in the placebo group and one in the BNT162b2-vaccinated group. The study’s data monitoring safety board (DMSB) has not reported any serious safety concerns related to the vaccine.

Based on current projections, Pfizer and BioNTech announced they expect to produce up to 50 million vaccine doses in 2020 and up to 1.3 billion doses by the end of 2021. Four of Pfizer’s facilities are part of the manufacturing and supply chain, and BioNTech’s German sites also will be leveraged for global supply.

Moderna’s Entry The mRNA-1273 (Moderna) COVID-19 vaccine candidate was the second to provide positive interim results in excess of 90%. The results emerged from the phase 3 randomized, 1:1 placebo-controlled COVE study testing mRNA-1273 at the 100-mcg dose level in 30,000 adults in the United States. In a prespecified interim analysis of 95 cases of COVID-19, 90 were observed in the placebo group versus five in the mRNA-1273 group, resulting in a vaccine efficacy of 94.5% (P<0.0001). A

Correction

he article, “COVID-19 Prompts a Second Look at CSTDs” (Pharmacy Practice News 2020;47[11]:38) mischaracterized the alignment and connection functions of BD’s closed system drug-transfer device (CSTD). The company’s BD PhaSeal Optima CSTD does not employ a push-and-click connection, as was stated. Instead, it uses a onestep straight push connection to connect with IV lines, rather than the older device’s push-turn-push manipulation. Additionally, the BD PhaSeal Optima CSTD does not employ any red alignment lines. Finally, the title of Ryan Forrey, PharmD, MS, BCSCP, FASHP, should have been updated to associate director of hazardous drug safety. We regret any confusion the errors may have caused.

secondary end point analyzed 11 severe cases of COVID-19; all 11 cases occurred in the placebo group, and none in the mRNA-1273–vaccinated group (N Engl J Med 2020;383:1920-1931). The Moderna vaccine was generally well tolerated, according to its DMSB. “The vaccines seem to have comparable efficacy,” said William Schaffner, MD, a professor of preventive medicine at Vanderbilt University, in Nashville, Tenn. “In addition to preventing mild to moderate illness, the Moderna vaccine also seems to prevent severe disease, so we look forward to Pfizer’s data on that.” He added that more information is needed about the vaccines’ effects in vulnerable populations. “The Moderna vaccine also may cause fewer side effects, such as sore arms or feeling fatigued, than the Pfizer vaccine,” but that needs confirmation, Schaffner said. Health and Human Services Secretary Alex Azar projected that by the end of December, about 40 million doses of both vaccines will be available for distribution, pending FDA authorization. Pfizer said it will be able to use its existing cold chain infrastructure to distribute the vaccine globally. Working with BioNTech, the company has developed temperature-controlled thermal shippers using dry ice to maintain temperature

EDITORIAL BOARD

conditions. The Pfizer/BioNTech vaccine needs to be stored and transported at -94° F. The Moderna vaccine, in contrast, can be shipped at temperatures “that are routine for many other vaccines in use,” Schaffner said. “That’s a distinct advantage” that will “allow much wider distribution to doctors’ offices, pharmacies and clinics, ... [and] bring the vaccine closer to the people rather than having to bring the people to the vaccine.”

Oxford, AstraZeneca Results The University of Oxford, in collaboration with AstraZeneca plc, announced interim trial data showing that its ChAdOx1 nCoV-2019 vaccine is 70.4% effective when combining data from two dosing regimens. When patients were given a halved first dose followed by a standard second dose, efficacy reached 90%. The researchers added that the vaccine “can be easily administered in existing health care systems, stored at ‘fridge temperature’ (35-46° F) and distributed using existing logistics.” —Marie Rosenthal Schaffner reported no relevant financial relationships.

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4 Up Front

Pharmacy Practice News • December 2020

COVID-19 Pandemic

Patient assistance program yields a $236,000 monthly ly windfall windfall ffor or h hospital ospital

PAPs Not Just for Patients P

atient assistance programs (PAPs) aren’t just for patients: Health systems also are benefiting as they use the programs to lessen the financial burden of high-cost medications during the COVID-19 pandemic. Phoebe Putney Memorial Hospital, in Albany, Ga., is a case in point. Clinicians at the hospital thought they were conducting business as usual in February, when they admitted and treated a patient visiting from Atlanta for chronic obstructive pulmonary disease and other concerns, and later released him. In a story covered widely by the media, the patient, who had come to town for a funeral, had COVID-19 but didn’t know it. That funeral later became known as a “super-spreader” event, leading to hundreds of people testing positive for the coronavirus. By the time health care workers at the hospital were notified that they were potentially exposed to the virus, it had been a week, said Marty Kelvas, DPh, RPh, the corporate director of pharmacy services at Phoebe Putney Health System. “It just mushroomed after that because there were no precautions taken at that time,” Kelvas said. “We found ourselves in the middle of a significant crisis, and had to make quick adjustments [sidebar].”

All Hands on Deck With an all-hands-on-deck effort required to care for COVID-19 patients, the last thing on Kelvas’ mind was looking for PAP help from drug manufacturers for indigent or uninsured patients, even when the hospital began using tocilizumab (Actemra, Genentech)—normally used for rheumatoid arthritis—to manage the exaggerated immune response known as a cytokine storm in some patients. That’s where their PAP partner, McKesson RxO, stepped in, he said. Program representatives contacted the pharmacy and worked with Genentech, which offered to provide replacement product for eight patients who qualified for assistance, amounting to about $18,000 in drug costs. The PAP team identified qualified patients by reviewing pharmacy claims to pinpoint where the hospital could receive product replacement for uninsured or self-paying patients. The program also can prospectively identify patients by looking at scheduling data, ensuring patients are enrolled in a timely manner, said O’Mally Monahan, MPH, the senior director of patient assistance services at McKesson. As regular operations slowly resumed, patient assistance recovery funds shifted more to other areas, such as outpatient

cancer therapies. In August 2020, the health system hit a record of $236,000 in recovered funds from PAPs, the most since starting its program 1.5 years ago, according to Kelvas. Health care experts expected to see a surge of need for PAPs at the beginning of the COVID-19 pandemic, Monahan said. “But because people started to social distance, and that included social distancing from medical care, that spike we expected wasn’t truly a spike,” she said. The initial increase was seen in certain geographic hot spots for COVID-19, such as the New York and New Jersey metropolitan area, Monahan said. “But patients and hospitals around the country who continued to receive benefits from their manufacturer-sponsored PAPs relied on the McKesson team heavily,” she said.

A Costly Path to the ER COVID-19 created illness that was “not ignorable,” said Mark Jordan, PharmD, the director of pharmacy at Yuma Regional Medical Center, in Arizona. “There are a lot of folks in our community who would benefit from health care services but don’t access them for all the usual reasons,” he said. “When it came to this pandemic, people who normally would not seek health care for their day-to-day ailments and needs really had no choice, so they would end up following the ER path into our hospital.”

Similar to Phoebe Putney Health, the nature of treating COVID-19 at Yuma Regional brought with it the use of novel medications such as remdesivir (Veklury, Gilead) and tocilizumab, so patient assistance became “even more valuable,” Jordan said. The PAP they use, also McKesson RxO, helped them recover “a significant number of tocilizumab doses used in that patient population,” he said. “Given that each dose cost us just over $2,000, the product replacement was meaningful.” Although PAPs are heavily regulated, Monahan said, drug manufacturers made several modifications due to the pandemic to make receipt of free and reduced-cost drugs easier for patients. For example, they allowed the use of electronic signatures so patients wouldn’t have to bring

Phoebe Putney’s COVID-19 Scramble

n the wake of a “super-spreader’ event, Phoebe Putney Memorial Hospital in Albany, Ga., was admitting up to 45 patients per day, many directly to its three critical care units, according to Marty Kelvas, DPh, RPh, the corporate director of pharmacy services at Phoebe Putney Health System. The emergency department was overwhelmed, he said. Personal protective equipment was running low, and the pharmacy was scrambling to get needed medications. The operating rooms were shut down except for emergency surgeries, and staff repurposed the postanesthesia care unit and another area to serve as two extra critical care units.

‘This was an unbelievable period of time. I’ve been practicing 44 years as a pharmacist, and I’ve never seen anything come close to this.’ —Marty Kelvas, DPh, RPh Meanwhile, the health system expanded one of its hospitals to handle the COVID-19 patients, and the hospital pharmacy, which normally closed in the evenings, had to rapidly convert to a 24/7 operation. Kelvas, who tested positive for COVID-19 in late March, found himself spending his recovery time at home on the phone interviewing temporary pharmacy staff. “We were basically trying to respond to this overwhelming crisis,” Kelvas said. “This was an unbelievable period of time. I’ve been practicing 44 years as a pharmacist, and I’ve never seen anything come close to this.” —K.B.

a physical application to the hospital. They also temporarily allowed patients to verbally confirm their income instead of requiring hard documents, and extended the reenrollment period for patients who normally renewed in March to July. Now is the time for hospitals to ensure they’re effectively using PAPs, Monahan advised. “We’ve seen hospitals take hard hits with the financial impacts of COVID-19,” she said. “Now they should be looking internally to say, ‘Are we doing this well?’ It’s real dollar savings to patients enrolled in PAPs, and hospitals receive medication back directly.”

Uptick in PAP Enrollment For some hospitals, having an avenue to help purchase therapeutics can reduce the financial burden of caring for uninsured patients, said Corey Ford, MHA, the director of reimbursement and policy insights at Xcenda, a consulting and reimbursement services firm. There has been an uptick in request for and enrollment in PAPs, Ford noted, which could result from unemployment benefits provided by the federal economic stimulus package running out. In addition, as medical offices have become more savvy in their protocols to protect patients from COVID-19, patients have slowly become more comfortable resuming medical visits and drug therapies, Ford said. A concern now, he added, is what to expect going forward. “Patients are still struggling with out-ofpocket costs to pay for their medications. This doesn’t appear to be the kind of V-shaped recovery that economists were predicting earlier in the spring; this is going to linger well into 2021. PAPs are really going to have to be prepared for this moving forward.” —Karen Blum The sources reported no relevant financial relationships other than their employment.

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6 Up Front

Pharmacy Practice News • December 2020

COVID-19 Pandemic

Meeting the COVID-19 Call continued from page 1

to people who were at high risk for COVID-19–related medical complications. Those who test positive for COVID-19 are housed in one of several quarantined alternative care centers, where pharmacists continue to provide oversight. The pharmacy team also provides personal protective equipment and sanitation training for shelter staff. During the initial part of the testing period presented at the meeting, in April 2020, the pharmacists were only able to access antibody testing for COVID-19, and in that time they conducted 83 such tests, only one of which was positive. In May 2020, the San Bernardino County Department of Public Health offered a supply pp y of oropharyngeal PCR tests, and because of the many limits of antibody testing, PCR testing was used exclusively

from then on. During the remainder of the testing period reported in the study (May-October 2020), pharmacists conducted 105 oropharyngeal PCR tests, of which 10 were positive for COVID-19 and 95 were negative. “Originally, the free clinic Symba Center was approached by the City of Victorville to offer medical oversight to all the shelters in the city. Our volunteer physicians were unable to commit to providing this service as a result of their full-time position demands at hospitals,” Smith told Pharmacy Practice News. “Therefore, the pharmacy team at Symba Center, which included two PharmDs and two to three APPE [Advanced Pharmacyy [ Practice Experience] rotation students, along with two nurses, took on this project on behalf of the city. We believe this project shows

that pharmacists providing services to underserved populations in community and clinic settings can partner with local shelters to implement a similar protocol to prevent COVID-19 spread in the homeless population.”

Auburn University Pharmacy Students Respond

‘We need to teach the next generation of pharmacists to have an open mind and provide the same level of care [to anyone], regardless of housing status or what someone looks like.’ —Shawn Smith, PharmD Shawn Smith, PharmD, documents intake forms for those seeking shelter at Victor Valley Community Warming Shelter in Victorville, Calif.

In the second study, pharmacy students from the Harrison School of Pharmacy at Auburn University, in Alabama, conducted a telephone survey to assess effects of the COVID-19 pandemic on patients with diabetes receiving care from Ozanam Charitable Pharmacy, which provides pharmacy services to the indigent and uninsured population of Mobile. The survey was designed to collect data on participants’ usual diabetes care, along with the pandemic’s effects on medication access and participants’ social and mental well-being. Between June 8 and July 20, 2020, the students, led by Kevin Astle, PharmD, BCPS, AAHIVP, an assistant clinical professor of pharmacy practice, reached out by telephone to 60 patients with a history of taking any antidiabetes medication. In this sample of vulnerable patients, 48% agreed or strongly agreed that diabetes takes up too much of their mental and physical energy. On question 1 of the Patient Health Questionnaire-2 depression screening test, 37.4% of patients reported having little interest or pleasure in doing things for more than half the days, nearly every day or every day. On question 2, 38.4% of patients reported feeling down, depressed or hopeless for the same periods of time. “Uninsured patients with diabetes are at an increased risk for worsening health and wellness status as a result of the COVID-19 pandemic,” Astle told Pharmacy Practice News. “The survey

also gave patients an opportunity for free response, and they reported a lot of intangible stressors faced with the COVID-19 pandemic and were overwhelmingly receptive to communicating with our pharmacy students for this project.” The investigators had hypothesized that, given the nature of the patient population, the burden of the pandemic would be felt similarly by everyone, but that’s not what they found. “In our anecdotal [experience], patients on the lower end of socioeconomic status had less of an impact than those who were at the upper end,” Astle said. “We believe this is due to the fact that those at the upper end had jobs beforehand or a stronger social network that was more disrupted than those at the lower end. This is an area that we have been investigating further.”

Going into the Streets The California and Alabama teams aren’t the only pharmacists working to increase access to care for indigent patients. Sorosh Kherghehpoush, PharmD, a research fellow at the Washington State University (WSU) College of Pharmacy and Pharmaceutical Sciences in Spokane, works with a street medicine team that also includes representatives of WSU’s Colleges of Medicine and Nursing to bring health services to homeless individuals in the area. Spokane’s shelters have had to reduce their capacity due to COVID-19, based on guidelines issued by the city in March; even so, in early November, 17 people at the Open Doors Shelter in East Spokane tested positive for the virus, turning the facility into a quarantine site. This means that Kherghehpoush and his team are finding more and more people in need on the streets and in encampments outside the city.

Up Front

Pharmacy Practice News • December 2020

COVID-19 Pandemic district follows up with these individuals,” Kherghehpoush explained. “Sometimes we revisit areas where we have previously gone, but the health district wouldn’t necessarily communicate with us to check up on a specific person; they use their own resources to follow up and educate people about next steps.” Many individuals without housing are reluctant to seek shelter in the current environment, Kherghehpoush added. “Several people I’ve spoken with have said they don’t want to even try to get into a shelter because of the risk of

being exposed to the virus. But for many people experiencing homelessness, they actually don’t see COVID-19 as that much of a threat—they’re not worried about a virus when they don’t even know where they’re going to sleep at night.”

Next Step: Expand the Street Medicine Team In 2021, Kherghehpoush noted, he will recruit student pharmacists to the street medicine team, as well as develop an elective course on working with vulnerable populations, including

those experiencing homelessness. “Evidence has shown that there’s a lot of stigma among health care providers when it comes to treating these people,” he said. “We need to teach the next generation of pharmacists to have an open mind and provide the same level of care they would to any other person, regardless of housing status or what someone looks like.” —Gina Shaw The sources reported no relevant financial relationships.

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Sorosh Kherghehpoush, PharmD, Washington State University (WSU) College of Pharmacy and Pharmaceutical Sciences (right), and Ron Rizzuto, from the WSU Elson S. Floyd College of Medicine, both in Spokane, in front of the Range Health Mobile Unit they use to conduct COVID-19 testing in rural areas.

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“We go out on average of about four times a week to various encampments, any place we can find,” he said. “We provide them COVID-19 screenings and testing, along with other primary care services such as medications for acute problems they might be having.”

Others Acting for Access Homeless people who are living in the heart of the city are more at risk for COVID-19, because they have more exposure to other people, but Kherghehpoush said they also have more access to health services, since they can often walk to federally qualified health centers. Individuals in encampments further outside the city center live a more secluded life, with less potential exposure to the virus, but they also tend to have more overall health problems, are much more difficult for medical teams to reach and have less access to care. His group first began screening homeless individuals for COVID-19 symptoms in March. Initially, they had very limited access to testing. “We were only allowed to test individuals who were symptomatic,” Kherghehpoush said. “If someone had potential exposure to the virus but was asymptomatic, we couldn’t test them. During the summer, we began to get more tests available to us, and now we are able to do about five to 10 tests a week.” Keeping connected to patients from these communities, however, is a challenge. “The Spokane regional health

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8 Policy

Pharmacy Practice News • December 2020

Reimbursement Matters

Charging into 2021 with a fresh new approach

Ringing in the New Payment Year M

oving into the new payment year for outpatient/ambulatory health care services requires some diligence on pharmacy’s part to ensure that nothing has been left undone. Complacency, financial naivete, apathy or inertia should all be left in the dust as you ring in the New Year with a fresh new approach. Here are some key issues needing your laser focus.

Payors: Who They Are, Who Negotiates With Them Looking into my crystal ball, I predict that payor requirements will continue to increase and it will be financially worthwhile to negotiate with payors for anything that brings in revenue and recognizes pharmacy for the extra work they do. The negotiations could touch on anything from handling fees for whitebagged drugs (sidebar) to any number of outpatient and ambulatory clinical services. The timing is good because you might be able to squeeze this into new payor contracts beginning in CY 2021. More on handling fees: These have been negotiated successfully by some hospitals and health systems, but there are several parameters that need to be met for this outpatient reimbursement strategy to work. One of the most important is to determine who the payor is. Let’s take a look at a few payor types: Traditional Medicare plan: These plans do not reimburse for medication handling fees.

Medicaid plans: These are state dependent, so payments for handling fees are unlikely. Medicare Advantage: Handling fee payments are possible from these commercial plans, but you’ll need to know the particular plan chosen by the patient. Commercial payors. As for the huge list of payors in the market, this is the group you'll want to be targeting. It’s important to note, however, that if your pharmacy is one of those that still does not automatically get payor information on every outpatient, that's the first hurdle to resolve.

in your facility negotiates payor agreements with commercial payors and work with that person/group to hone your “ask sheet.” They’ll be presenting the ask to the payor, not you. But you’re the only one who knows what the ask is for, so you need to convey that in clear terms and ensure complete understanding. Avoid being turned down, led astray or otherwise derailed because of not understanding the nuance between an “administration fee” and a “handling fee.” There’s a difference between drug administration fees, which are very clearly defined, and drug handling fees,

Every clean, complete Medicare claim gets a 2% increase in payment as long as sequestration is in effect. That’s an extra $200,000 for every $10 million CMS pays out. Prepare your “ask” document, not longer than one page, to be used for negotiations with the payor. Include a brief background of why you’re asking, what the ask covers and how much you’re asking for. Work with your finance and revenue cycle teams to determine how and when medication handling fees will be billed and include these details. It’s not an “auto add-on charge”; rather, it’s a patient-specific add-on charge for a specific payor when a specific white-bagged drug is used. No “robo-billing” here. The next step is to determine who

which you are trying to negotiate with the payor, and don’t include any drug preparation supplies. Handling fees do include everything that you must do to be able to acquire, store and use the patient-specific whitebagged drug. Make your list and price it out to determine the fee you’re asking for. Keep it reasonable; look at what drug admininstration reimbursement codes cover and their payment. What expenses are you trying to recoup money for? Staff time? Information technology/other infrastructure modifications (one-time cost)? How about refrigerated storage (one-time cost), nonrefrigerated storage (one-time cost) and discontinued drugs/ return handling? Requests for payment for clinical services outside of Medicare/Medicaid would follow the same preparation path, whereas those for Medicare/Medicaid are clearly defined in their rule sets.

Transparency in Hospital Pricing

What Is White Bagging?

hite bagging is the practice of having patient-specific medications or supplies delivered directly to the practice setting (outpatient infusion center, physician office, hospital) for use by a specific patient. The specialty pharmacy shipping the product directly to the practice site has already billed the insurance company for the product and collected the copay from the patient or secondary insurer. There is no opportunity for the practice site to bill for the product; it is prepaid or complimentary. The practice evolved due to some insurance carriers mandating that patients and providers use specialty pharmacies to obtain their medications. Manufacturer-supported patient assistance programs and some FDA-assigned Risk Evaluation and Mitigation Strategy programs also are cited as reasons why specialty pharmacies become the mandated source for prescription dispensing. (Clear bagging, a related process, is the term used when the health care system supplies the medications from its own specialty pharmacy.)

There are several key CMS payment provisions that will take effect over the next few years that you and your revenue cycle team need to know: 2021: CMS rules issued Nov. 14, 2019, require hospitals to provide an out-ofpocket price estimator tool or information on 300 “shoppable” services (70 CMS set, 230 facility selected) for patients as well as disclose their privately negotiated rates with health insurers. Are you part of the team determining which shoppable services will be offered, showcased or used as a marketing tool? Does your CDM support this, or are there significant changes needed at least to the segments affected by the services chosen? For example, if infusion services are selected, then focus

“Reimbursement Matters” is a tool for maintaining your health system’s fiscal health. Please email the author at bonniekirschenbaum@ gmail.com with suggestions on reimbursement issues that you would like to see covered.

Bonnie Kirschenbaum, MS, FASHP, FCSHP

the CDM redo on the applicable drugs and drug administration services. 2022: Insurers must post online a series of documents that include their in-network negotiated provider rates, out-of-network coverage rates and innetwork drug pricing. The drug pricing requirement was newly added to the finalized version of the rule. 2023: Insurers will be mandated to offer an online shopping tool or similar platform that includes an out-of-pocket cost estimate and negotiated prices for 500 of the “most shoppable” services, and in 2024, this requirement will be extended to all services.

Clean Up Your Claims The quality of the reimbursement data you generate and document is critical to ensuring maximum payments not only for your hospital but others, since CMS bases payments at least in part on those data. To that end, are you proactive or reactive in this process? Are you wasting time chasing after denied codes rather than doing it right the first time? Bringing together people, processes and technology to deliver patient care and capture the necessary codes is essential to close the gap between clinical care and actual reimbursement. From a pharmacy perspective, there are several components to billing for a drug and its administration. Some are payor determined and some, such as HCPCS, CPT and ICD10 codes, are set by national issuing organizations. At minimum, a complex Medicare Part B drug and its administration begins with knowing who the payor is and specific drug requirements. Start with prior authorization, where the patient's disease state must match the payable ones, with EHR documentation supporting ICD-10 code assignment. NCD/LCD assignments, clearly spelled out on your MAC's website, apply to Medicare patients. Here are some added factors to consider: HCPCS code assignment: Use quarterly ASP tables or Addendum B on the cms.gov website. Revenue cycle teams automatically get these quarterly updates and other changes electronically. Complete HCPCS lists are supplied by “source of truth” pharmacy computer system

Policy

Pharmacy Practice News â&#x20AC;˘ December 2020

Reimbursement Matters

A Reimbursement Lexicon ASP, average sales price; CDM, charge description master; CMS, Centers for Medicare & Medicaid Services; CPT, Current Procedural Terminology; CY, calendar year; EHR, electronic health record; HCPCS, Healthcare Common Procedural Coding System; ICD-10, International Classification of Diseases, Tenth Revision; LCD, local coverage determination; MAC, Medicare administrative contractor; NCD, national coverage determination; REMS, Risk Evaluation and Mitigation Strategies; SI, status indicator

vendors. Check with your informaticist (in-house or contracted). Some payors also require the NDC number. Drug administration fees: These are available even if the drug is not separately paid for (SI N), is white or clear bagged, or even as a patient assistance drug. Match the Part B drugs you routinely dispense to the applicable code for your revenue cycle team. Under no circumstances should they be stripping out or putting a hard stop to drug administration fees for $0 priced or SI N drugs. Still not convinced? Then consider this: Every clean, complete Medicare claim gets a 2% increase in payment as long as sequestration is in effect. Thatâ&#x20AC;&#x2122;s an extra $200,000 for every $10 million CMS pays out. Specialty pharmacy: Your organization needs a strategy that addresses the acquisition, handling and use of specialty pharmacy products as well as payor requirements that often change annually. Whether your system has built its own specialty pharmacy or has partnered with commercial source(s), a thorough review of whatâ&#x20AC;&#x2122;s changed and expected for the 2021 payment year is essential. This review includes formulary changes and prior authorization requirements, among others. Supply chain partners have expanded from traditional wholesalers to include specialty pharmacies and mandated drug distributors. Managing these relationships must be evaluated and changes implemented moving into a new payment year. Payment rule changes: A few years ago, budgetary imbalances triggered a 2% sequestration cut on the 80% Medicare payment (20% patient copays werenâ&#x20AC;&#x2122;t affected). The temporary pandemic lift expires Dec. 31, 2020. Congressional leaders are urged to pass legislation extending the moratorium into 2021 and through the duration of COVID-19. Major evaluation and management changes effective Jan. 1, 2021, are designed to reduce COVID-19â&#x20AC;&#x201C;related provider burdens while focusing on patient care and management. Pharmacy must understand the difference between current and 2021 guidelines, including the current use of time and the 2021 report of time as well as when it is appropriate to report the new prolonged service code. This affects incident to and collaborative practice relationships. Site of care: Has your facility identified specific, implementable

strategies to proactively increase access to care for those in your patient pool whoâ&#x20AC;&#x2122;ve shifted to other sites of care during the COVID-19 pandemic? How are you tracking therapeutic switches? Are your specialty physicians opting for oral medications over infusions and injectable products, to keep immunologically compromised patients adhering to

those medications at home? Is this a loss of revenue for your facility, or has your organization opted to expand and operate those alternative sites of care? How is your pharmacy supporting this? Telehealth: Growth in telehealth services has sped up during the pandemic, but its continuation rests on several factors, including CMS and commercial payors extending payment for telehealth and virtual care services. The Joint Commission released a new Quick Safety advisory outlining the benefits and hurdles of telehealth. It recommends providers

set key metrics (number of patients seen, reductions in no-shows) and ensure vendors can provide easy access to necessary data. Others include giving clinicians realtime access to patient data and integrating remote patient monitoring into the EHR (e.g., temperature, pulse oximetry, blood pressure and glucose; bit.ly/2UkVYov). Additionally, CMS has released two updated and helpful tool kits to assist with understanding the nuances of implementing telehealth during the pandemic (bit.ly/3eULhCp; bit. ly/2GYQ9tY). â&#x2013;

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10 Clinical

Pharmacy Practice News • December 2020

Infectious Disease

Part 2 of a 2-part series: overcoming challenges

Taking Stewardship Out on the Town W

ith up to 50% of outpatient-prescribed antibiotics written for an inappropriate indication, drug, dose or duration (JAMA 2016;315[17]:1864-1873), regulatory organizations have taken steps to shave that number down—and pharmacists are also doing their part. In 2016, the CDC published its core elements of outpatient antimicrobial stewardship programs (ASPs) (bit.ly/ 32WrYUx) and, as of January 2020, the Joint Commission (TJC) requires ambulatory health care organizations to meet similar elements of performance for antimicrobial stewardship within the Medication Management (MM) chapter

(Standard MM.09.01.03), if they want to be TJC certified. Despite the accelerated push by many professional societies and regulatory bodies to incentivize health systems to develop outpatient solutions, “most health-system dollars are still directed inward, when it comes to ASPs,” said Dominic Chan, PharmD, an infectious diseases specialist and pharmacy clinical coordinator/co-director of the ASP at Legacy Health in Oregon and Southwest Washington. “The enormity of the differences between the inpatient and outpatient settings” could be part of the reason health systems are putting off

allocating more resources to outpatient ASPs, he added. For example, although g medication administration dataa available through inpatient electronicc health records provide important informaformation, outpatient information technolhnology systems often are limited to prescribing and dispensing data,, which require making assumptions about actual medication use. Moreover, “the patient– clinician dynamic is different, and patients in the outpatient setting may have a higher degree of entitlement and demand for antibiotics, as opposed to the fairly clinician-borne unilateral decisions made in the inpatient setting,” Chan said. “Time is another key bottleneck when it comes to appropriate [outpatient] antimicrobial prescribing.”

A Success Story

5 Keys to Outpatient ASP Success

onsidering implementing an antimicrobial stewardship program in the outpatient setting? Lisa Dumkow, PharmD, BCIDP, a clinical pharmacist in infectious diseases and antimicrobial stewardship at Mercy Health Saint Mary’s, in Grand Rapids, Mich., has some tips based on her team’s successes doing so at four outpatient primary care clinics.

Reach out to clinicians. The first thing to consider is your approach to clinic providers, she noted. “Rather than assuming you know everything and that what you do is right, speak with clinicians about their prescribing practices and ask why they are prescribing the way they are, without being accusatory.” By understanding the specific challenges they face, you can develop better solutions, she said. “One of the main things that’s frustrating for us as stewardship experts is that we encourage physicians to watch and wait with most patients, but they may be concerned about their patient satisfaction scores.” Key on patient satisfaction. In response to patient satisfaction concerns, she said her team reminds providers that patients will likely be just as dissatisfied with receiving an antibiotic that they don’t need—since they most likely have a viral infection— and not feeling better after treatment. They recommend that providers prescribe supportive care measures, such as inhalers, saline nasal spray and cough suppressants, “so that patients don’t leave an appointment with nothing,” she said. Get support from pharmacy leadership. This should be done throughout the health system to ensure there are adequate resources and enough time to perform stewardship activities at the outpatient sites. Don’t forget residents. “Engage your residents because they can be very helpful,” she said, recalling a pharmacy student and resident who helped them collect and organize their data for analysis and presentation. Serve as an educational resource for the outpatient team. “Be approachable and be kind, and provide contact information so that they can call either you or someone else with questions,” she said. “We also like to provide in-person education whenever possible because that puts a face to the name.”

—D.W.

Mercy Health Saint Mary’s, in Grand Rapids, Mich., provides a case study in how these challenges can be overcome. Lisa Dumkow, PharmD, BCIDP, an infectious diseases pharmacist at the health system, noted that the organization decided to add ASPs to its primary care locations in August 2017. “We were somewhat ahead of the game, because we already had several of the CDC’s core elements in place in these locations—things like outpatient antibiograms and annual education for all office staff—and we expected upcoming TJC requirements to closely resemble these CDC elements,” she said. Mercy Health initiated a pilot ASP at one of its 22 primary care offices, collaborating with the on-site clinical ambulatory care pharmacist who had antimicrobial stewardship training, and a physician who had an interest in antimicrobial stewardship and championed the initiative to other office clinicians and staff. “Given the CDC core elements and TJC requirements, we were able to make a case to pharmacy leadership that secured a half-day per week for the on-site pharmacist to devote to stewardship activities,” Dumkow said.

As a next step, members of system’s ASP team the health system worked with the on-site pharmacist to get a clear picture of prescribing patterns at the site. They analyzed a sample of more than 8,000 antimicrobial prescriptions written during a sixmonth period and found that half of these were for upper respiratory tract infectionsm (URTIs), 30% were for skin and soft tissue infections, and just over 10% were for urinary tract infections (UTIs). The remaining 10% of prescriptions were for a variety of indications, most commonly for dental infections and prophylactic indications. When they homed in on UTI prescribing, they found that only 20% of antimicrobial prescriptions were for a guideline-appropriate agent, only 55% were for a guideline-appropriate duration of treatment, and 25% of patients were asymptomatic and did not meet the criteria for treatment of UTIs. “We found that fluoroquinolones ones were the most commonly used antimicrobials for UTIs, which is inapnappropriate, so we decided to tarrget UTI prescribing along with h upper respiratory tract infections ns as our first two disease states,” es ” Dumkow said. Along with an infectious disease pharmacist and physician from the hospital, Dumkow and the on-site pharmacist held a “lunch-and-learn” at the primary care site, presenting staff with the findings of their analysis and performing deeper dives into the treatment of 30 patients with UTIs and 30 with URTIs. “The patients represented both appropriate and inappropriate prescriptions, and many met criteria for ‘watch and wait’ before they needed antibiotics,” she said. “We provided staff with education on their antibiogram and on local guidelines, and we gave them pocket guides with the antibiogram and guidelines.” Dumkow cited another important part of the ASP: the time the on-site pharmacist spends during their half day of ASP activities reviewing each antimicrobial prescribed during the previous week. For each prescription, they provide

Clinical

Pharmacy Practice News • December 2020

Infectious Disease researchers, the pilot project’s success has led to the implementation of an ASP at all four of the health system’s outpatient offices that have an ambulatory care pharmacist. Those outpatient locations also have experienced significant improvements in appropriate antimicrobial prescribing. “Now, we’re grappling with how to implement ASPs at the 18 primary care offices where there is no on-site pharmacist,” Dumkow said. “One possibility is that as we roll out a new electronic medical record system in 2020, we could use the prescribing physician a letter thanking them for their work and either commending their appropriate prescribing or encouraging them to follow guidelines if their prescription was inappropriate. Provider response to these letters has been very positive, Dumkow said. Physicians have reported “a collaborative feeling of learning and of bettering our

order sets to implement some prescribing best practices.” Another way they might expand their ASPs to additional primary care locations without an on-site pharmacist is by having an off-site team periodically audit a clinic’s prescribing and provide feedback to providers, she added. “We’ve got a long way to go, but this has been one of the most exciting projects we’ve done over the last few years.” Organizations that are stretched for resources but want to implement an ASP in outpatient settings such as primary

The sources reported no relevant financial relationships.

THE PEAK OF PREPARATION.

TJC’s 5 Elements of Performance for Ambulatory Care ASPs

UTI Rx Successes Percentage of fluoroquinolones prescribed for UTIs dropped from 85% to 10%.

Identify an antimicrobial stewardship leader responsible for developing, implementing and monitoring activities to promote appropriate antimicrobial medication prescribing practices.

Use of more appropriate betalactams increased from 5% to 50%. Prescriptions for nitrofurantoin— first-line therapy for uncomplicated UTIs in healthy adult women—went from 0% to roughly 40%.

Set at least one annual antimicrobial stewardship goal, such as decreasing use of antibiotics to treat viral infections.

UTI, urinary tract infection Source: Lisa Dumkow, PharmD

patients, and of having a nonpunipa tive cculture. Additionally, the feedback part of the initiative has sparked some friendly competition amongst providers to see who could receive the most positive [provider] feedback each week.” The ASP also has improved antimicrobial prescribing. A post-implementation analysis of 1,107 antimicrobials prescribed for UTIs over seven months showed that fluoroquinolones dropped from 85% to 10%, while use of more appropriate beta-lactams increased from 5% to 50%. Nitrofurantoin, which is the Infectious Diseases Society of America’s first-line recommended therapy for uncomplicated UTIs in healthy adult women, had not been previously prescribed and now accounted for roughly 40% of UTI antimicrobial prescriptions, they reported. Their post-ASP analysis also showed that the duration of antimicrobial therapy more closely reflected guidelines, with all but nine beta-lactam prescriptions written for seven days, clinicians prescribing more three-day courses of therapy, and nitrofurantoin prescriptions written for no more than five days, Dumkow noted. According to the

care clinics should identify “empowered and passionate partners in the outpatient setting, and not let a lack of infectious disease or antimicrobial stewardship training be a bottleneck,” Chan commented. “It will take time, but as the saying goes, ‘Faster alone, further together.’” To access Part 1 of this series, “Outpatient Antibiotic Stewardship Spreads Its Wings,” see www.pharmacypractice news.com. —David Wild

Implement evidencebased practice guidelines related to the annual goal. Provide clinical staff and licensed independent practitioners with educational resources related to the goal that promotes appropriate medication prescribing practices. Collect, analyze and report data pertaining to the goal to organizational leadership and prescribers. Examples include data on antimicrobial prescribing patterns, resistance patterns or evaluation of stewardship activities. You need to be prepared at all times. No one understands this more than CAPS®—

we’ve got you covered with three FDA-registered 503B outsourcing facilities and Source: The Joint Commission R3 Report the largest network of state-licensed 503A pharmacies in the country.

Issue 23. https://www.jointcommission.org/ en/standards/r3-report/r3-report-issue23-antimicrobial-stewardship-in-ambulatoryhealth-care/.

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12 Clinical

Pharmacy Practice News • December 2020

Review Article

Immunotherapy Toxicities: Early Recognition, Management, And Concerns in the COVID-19 Pandemic SAMANTHA SPENCER, PHARMD, BCPS Clinical Assistant Professor University of Illinois at Chicago Drug Information Group Chicago, Illinois

mmune checkpoint inhibitors and adoptive cell transfer therapies have unlocked new avenues to treat cancer, but they are associated with immune-related adverse events (irAEs).

Pharmacists can play an integral role in managing these irAEs and educating patients and other health care professionals about them. The immune system recognizes tumors and eradicates cancerous cells through T cells and natural killer cells,1 but to ensure that T cells do not autoreact to normal cells, the body has mechanisms that downregulate their activity as needed.2 Checkpoint pathways regulate T cells to prevent autoimmunity through a process called peripheral tolerance. To evade detection by T cells, cancer cells hijack this mechanism. Checkpoint inhibitors enable the immune system to better recognize and eliminate cancerous cells that are evading the immune system this way.2 Several checkpoint pathways regulate T cells, including the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed death-1 (PD-1) pathways.2 The CTLA pathway regulates the early stages of T-cell activation, and most expression is found in lymphoid tissue. In contrast, PD-1 regulates previously activated T cells in the later stages of the immune system response and is found mostly in peripheral tissues. Inhibition of CTLA-4 and PD-1—or its ligand, programmed death ligand-1 (PD-L1)— restores the immune system’s ability to respond to tumors. These pathways have been successfully targeted and have led to the approval of 6 checkpoint inhibitors (Table 1).3-12 Adoptive cell transfer therapy is another approach that has been developed to increase the immune system’s ability to target tumors.1 Specifically, in chimeric antigen receptor (CAR) T-cell therapy, T cells are harvested from a patient, genetically modified to express CARs, multiplied, and reinfused into the patient. Three such therapies are approved by the FDA: axicabtagene ciloleucel (Yescarta, Kite) tisagenlecleucel (Kymriah, Novartis), and brexucabtagene autoleucel (Tecartus, Kite) (Table 1). All express a CAR with an anti-CD19 chain, which allows the modified T cells to recognize and eliminate CD19-expressing cells.3,4,12

Checkpoint Inhibitors IMMUNE-RELATED ADVERSE EVENTS Due to their novel mechanism of action, checkpoint inhibitors are not associated with the

traditional AEs seen with cytotoxic chemotherapy.13 However, inhibition of CTLA-4, PD-1, and PD-L1 can lead to excessive immune system activation with upregulation of T-cell proinflammatory responses.13-15 This activation of the immune system can result in irAEs. The exact mechanism of irAEs has not been elucidated fully, but it is hypothesized that T-cell activity, autoantibodies, and proinflammatory cytokines may contribute to their development. Dermatologic, gastrointestinal, endocrine, and pulmonary-related irAEs are the most common irAEs, but they can manifest in any organ system. The CTLA-4 inhibitor ipilimumab (Yervoy, Bristol-Myers Squibb) is associated with the highest rates of irAEs; 75% of patients will experience an irAE and one-fourth will have a high-grade irAE.13,15 Dermatologic and gastrointestinal events have been reported most commonly.13 Phase 3 trials of the PD-1/PD-L1 inhibitors reported lower rates, with no more than 30% of patients experiencing an irAE.13,15 In patients receiving combination checkpoint inhibitor therapy (ie, nivolumab [Opdivo, Bristol-Myers Squibb] with ipilimumab), almost all experience an irAE (96%) and over half (59%) develop a high-grade irAE. The rates of irAEs also vary based on the underlying cancer, and for ipilimumab and pembrolizumab (Keytruda, Merck) the toxicity is dose dependent. Most irAEs experienced by patients receiving checkpoint inhibitors are mild to moderate, but severe events, including fatal ones, can occur with these agents. Rash and pruritus are the most common dermatologic irAEs, and they typically present as a lowgrade reaction.13 Dermatologic toxicities occur in approximately 30% to 40% of patients receiving PD-1/PD-L1 inhibitors and 50% of those receiving ipilimumab.15 Patients with melanoma have been observed to experience more dermatologic irAEs than patients with other underlying cancers.16 Diarrhea is another frequent irAE, with ipilimumab associated with the highest rates of occurrence (23%-41%). Additionally, colitis occurs in 7% to 16% of patients receiving ipilimumab and in 1% to 3% of patients receiving PD-1/PD-L1 inhibitors. Endocrine irAEs occur less frequently, but hypothyroidism,

hyperthyroidism, and hypophysitis have been reported most frequently among the endocrinopathies. Pneumonitis is rare (<1% with ipilimumab; 1%-3% with PD-1/PD-L1 inhibitors) but can lead to serious consequences. A number of additional irAEs have been reported, but many occur at a much lower incidence. The average onset of these irAEs varies, with dermatologic reactions presenting within 2 to 3 weeks and gastrointestinal, hepatic, and endocrine toxicities occurring after 2 to 3 months of therapy.14,16 However, the range for onset is broad, with some irAEs taking up to 2 years to appear,16 and they sometimes occur weeks or months after discontinuation of the medication.14 MANAGEMENT

OF IRAES

Patients increasingly are presenting with irAEs outside of the oncology space.14 Recognition of irAEs generally begins with a detailed medication history, including past medications because irAEs can occur even after discontinuation of a checkpoint inhibitor. A recent study reported that diarrhea was the most common irAE that led to patient presentation in an emergency department (ED).17 Other irAEs frequently observed in the ED included colitis, pneumonitis, dermatitis, hypophysitis, and hepatitis. Mild irAEs typically can be managed while the patient continues checkpoint inhibitor therapy, with a few exceptions.13,17 More severe toxicities generally require discontinuation of therapy. Corticosteroids are a cornerstone of irAE management and are recommended in the treatment of most reactions.13,16 Thyroid-related irAEs are a notable exception; clinicians do not use corticosteroids as part of the management of thyroid-related irAEs, except in cases of severe hyperthyroidism that may progress to thyroid storm.18 Guidance on steroid dosing can be found in clinical guidelines and the prescribing information for individual drugs.5-13,18 Generally, higher corticosteroid doses are reserved for moderate and severe irAEs.13 Additionally, the decision to use corticosteroids must consider patient-specific factors, such as comorbid conditions, type and number of irAEs,

Clinical

Pharmacy Practice News • December 2020

Review Article

IMMUNOTHERAPY

Table 1. FDA-Approved Immunotherapies

continued from page 12

concurrent immunosuppressive therapies, and the ability to tolerate corticosteroids. Specific guidance on irAE management can be found in practice guidelines by the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network.13,18 The ASCO guideline has detailed information about the grading and management of irAEs.18 A few examples outlining the recognition and management of irAEs are presented in Table 2.13,18 For high-grade toxicities, more aggressive management is needed and should be provided in conjunction with a specialist referral.13,18

Class

Drug

Initial Approval Date

Checkpoint inhibitors CTLA-4 inhibitor

Ipilimumab (Yervoy, Bristol Myers Squibb)

2011

• CRC, metastatic or metastatic MSI-H • HCC • Melanoma, unresectable or metastatic • NSCLC, recurrent or metastatic • RCC, advanced

PD-1 inhibitor

Cemiplimab (Libtayo, Regeneron)

2018

• cSCC, metastatic or locally advanced

Nivolumab (Opdivo, Bristol Myers Squibb)

2014

• cHL, relapsed • CRC, metastatic MSI-H or dMMR • ESCC, unresectable, recurrent, or metastatic • HCC • HNSCC, recurrent or metastatic • Melanoma, unresectable or metastatic • Mesothelioma, unresectable • NSCLC, recurrent or metastatic • RCC, advanced • SCLC, metastatic • UCC, recurrent or metastatic

Pembrolizumab (Keytruda, Merck)

2014

• Cervical cancer, recurrent or metastatic • cHL, relapsed or refractory • CRC, MSI-H or dMMR • Cutaneous SCC, recurrent or metastatic • Endometrial carcinoma, advanced • ESCC, recurrent or metastatic • Gastric cancer, recurrent or metastatic • HCC • HNSCC, recurrent, unresectable or metastatic • Melanoma • Merkel cell carcinoma, recurrent or metastatic • MSI-H cancers, unresectable or metastatic • NSCLC, unresectable or metastatic • PMBCL, relapsed or refractory • RCC, advanced • SCLC, metastatic • TMB-H solid tumors, unresectable or metastatic • TNBC, recurrent unresectable or metastatic • UCC, locally advanced or metastatic

Atezolizumab (Tecentriq, Genentech)

2016

• TNBC, unresectable or metastatic • HCC, unresectable or metastatic • Melanoma, unresectable or metastatic • SCLC, extensive-stage • NSCLC, metastatic • UCC, locally advanced or metastatic

Avelumab (Bavencio, EMD Serono)

2017

• Merkel cell carcinoma, metastatic • RCC, advanced • UCC, locally advanced or metastatic

Durvalumab (Imfinzi, AstraZeneca)

2017

• NSCLC, unresectable stage III • SCLC, extensive-stage • UCC, advanced or metastatic

IRAES CONSIDERATIONS WITH COVID-19 The novel 2019 coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has introduced potential complications in patients with cancer. Particularly relevant to checkpoint inhibitor therapy is the overlap of symptoms of COVID-19 with immunerelated pneumonitis.19 Appropriate recognition of symptoms is imperative to ensure patients receive optimal treatment. While the clinical presentation of COVID-19 still is being characterized, the most common symptoms are fever, cough, and dyspnea.20 With pneumonitis, dyspnea and cough are common, with fever occurring less frequently.19,21 Given these overlapping symptoms, it is critical for patients taking checkpoint inhibitors to quickly recognize and contact their health care provider about any of these core symptoms. COVID-19 testing and radiological findings can aid in the differential diagnosis to quickly determine the appropriate course of therapy and whether corticosteroids, which have a controversial role in COVID-19 treatment outside of severe cases, should be initiated.

CAR T-Cell Therapy CYTOKINE RELEASE SYNDROME

PD-L1 inhibitor

Axicabtagene ciloleucel, brexucabtagene autoleucel, and tisagenlecleucel contain boxed warnings in their prescribing information and are only available through a Risk Evaluation and Mitigation Strategies (REMS) program to moderate the risks of therapy, including cytokine release syndrome (CRS).3,4,22,23 Infusion of CAR T cells leads to a state of increased circulating proinflammatory cytokines coupled with suppression of anti-inflammatory cytokines.1,24 This imbalance causes CRS and, specifically, the activation of interleukin (IL)-6 contributes to capillary leak syndrome. CRS presents as fever, myalgias, and malaise that can progress to potentially fatal or life-threatening manifestations, including hypoxia, pulmonary edema, hemodynamic instability, renal and/or hepatic dysfunction, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome.1,13 Almost all patients receiving axicabtagene ciloleucel (94%) had CRS (any grade) in its clinical trial.3 Any grade of CRS was reported in 79% and 74% of patients receiving tisagenlecleucel for relapsed/refractory acute lymphoblastic leukemia and relapsed/refractory diffuse large B-cell lymphoma in clinical trials, respectively.4 Most often, CRS presents within 2 to see IMMUNOTHERAPY, page 14

Current FDA Indicationsa

Chimeric antigen receptor T-cell therapy CD-19 T-cell immunotherapy

Axicabtagene ciloleucel (Yescarta, Kite)

2017

• B-cell lymphoma, relapsed or refractory

Brexucabtagene autoleucel (Tecartus, Kite)

2020

• Mantle cell lymphoma, relapsed or refractory

Tisagenlecleucel (Kymriah, Novartis)

2017

• B-cell acute lymphoblastic leukemia, relapsed or refractory • Large B-cell lymphoma, relapsed or refractory

As of November 24, 2020; see prescribing information for details on the specific place in therapy within these indications.

cHL, classical Hodgkin lymphoma; CRC, colorectal cancer; cSCC, cutaneous squamous cell carcinoma; dMMR, mismatch repair deficient; ESCC; esophageal squamous cell carcinoma; HCC, hepatocellular carcinoma; HNSCC, head and neck squamous cell carcinoma; MSI-H, microsatellite instability-high; NSCLC, non-small cell lung cancer; PMBCL, primary mediastinal B-cell lymphoma; RCC, renal cell carcinoma; SCLC, small cell lung cancer, TMB-H, tumor mutational burden-high; TNBC, triple negative breast cancer; UCC, urothelial carcinoma Based on references 3-12.

14 Clinical

Pharmacy Practice News • December 2020

Review Article

IMMUNOTHERAPY continued from page 13

3 days after CAR T-cell infusion and persists for approximately a week.13 However, patients should be monitored for signs and symptoms of CRS for 4 weeks after CAR T-cell therapy.22,23 MANAGEMENT

CRS

Management of CRS is critically dependent on early recognition of symptoms to reduce the risk for a fatal outcome.1 The IL-6 receptor antagonist tocilizumab (Actemra, Genentech) is an important component in treating CRS.25 In an analysis of clinical trials for axicabtagene ciloleucel and tisagenlecleucel, 53% to 69% of patients with severe or life-threatening CRS resolved their fever and need for vasopressors within 14 days after 1 or 2 doses of tocilizumab.26 For patients presenting with a fever not attributable to another cause, symptomatic management and administration of empirical antibiotics is appropriate.13 For prolonged (>3 days) or highergrade CRS (grade 2 or higher), tocilizumab is recommended. The dosing is 8 mg/kg (maximum, 800 mg) given via IV infusion over 1 hour.13,25 For patients weighing less than 30 kg, a dose of 12 mg/kg should be used instead.25 Tocilizumab can be repeated as needed every 8 hours, with a maximum of 3 doses in 24 hours or 4 doses overall.

For grades 3 and 4, IV corticosteroids should be given with tocilizumab therapy.13 Vasopressors and other therapies to manage hypotension and hypoxia also should be used when needed.

The Pharmacist’s Role Pharmacists are in a unique position to educate providers and patients about potential AEs, recognition of symptoms, and management of immunotherapy toxicities.27 Early recognition and management of irAEs is critical for patients. Patient education for checkpoint inhibitors should focus on potential signs and symptoms and encourage patients to report any concerning symptoms quickly.28 Patterns of irAE incidence, including the type of irAE, prescribed checkpoint inhibitor, and underlying risk factors, should be considered.27 In addition, as corticosteroids are a foundation of treatment, pharmacists can assist in initial prescribing and tapering strategies. Tapers should last at least 4 weeks but should be individualized, as patients with corticosteroid-refractory disease may require a longer taper (6-12 weeks).27 There is no universal recommended tapering strategy, but the length of the taper is dependent on the severity and type of irAE.29 During any tapering strategy, close monitoring is warranted because the irAE can rebound. In addition, to help mitigate the risk for corticosteroid

Table 2. Management of Selected Low-Grade Immune-Related AEs Toxicity Rash

Diarrhea/ colitis

Signs and Symptoms

Other Considerations

Management

• Erythematous or maculopapular rash, frequently affecting the upper trunk • Pruritus • Vitiligo • Blistering, skin sloughing, and severe cutaneous irAEs (SJS, TENS) are treated more aggressively

• Typically presents during the first 2 treatment cycles • Ipilimumab is associated with higher rates of dermatologic irAEs compared with PD-1/PD-L1 inhibitors

• Continue ICPi for grades 1 and 2; hold with higher grades • Topical emollients, topical corticosteroids, and oral antihistamines • For more moderate symptoms, higher potency topical corticosteroids may be needed • Consider initiating oral corticosteroids for moderate symptoms (prednisone 0.5-1 mg/kg/day until back to grade 1, then taper over 4-6 wk)

• Watery diarrhea • Increase in stool count • Blood or mucus in stool • Abdominal pain, cramping

• Typically presents 6 to 8 weeks after starting treatment • Ipilimumab is associated with higher rates of gastrointestinal irAEs compared with PD-1/PD-L1 inhibitors

• Consider holding ICPi with grade 1; hold with higher grades • Oral hydration and dietary changes • Loperamide for 2-3 d • Consider initiating oral corticosteroids for grade 2 (prednisone 1-2 mg/kg/day until back to grade 1, then taper over 4-6 wk)

• Median time to onset is 2.5 months; earlier onset with combination therapy • PD-1/PD-L1 inhibitors are associated with higher rates of pulmonary irAEs compared with ipilimumab

• Hold ICPi with evidence of pneumonitis progression • For grade 2, oral corticosteroids (prednisone 1-2 mg/kg/day, then taper over 4-6 wk) • Consider empirical antibiotics

Pneumonitis • Dyspnea, cough • Chest pain • Difficulty with breathing (grade 1 – asymptomatic)

AEs, gastrointestinal bleeding prophylaxis and Pneumocystis jirovecii prophylaxis should be considered.15 For CAR T-cell therapies, detailed information on the management of CRS can be found in the REMS programs for axicabtagene ciloleucel, brexucabtagene autoleucel, and tisagenlecleucel.22,23 Of note, hospitals that treat patients

Table 3. Key Education Points for Pharmacists Pearls on Use of Corticosteroids for irAEs • Prednisone is recommended if a patient can tolerate oral therapy; otherwise, IV methylprednisolone can be used. • Short-term use does not affect the antitumor efficacy of the checkpoint inhibitors. • Patients should expect some response within 48 to 72 hours of initiation; dose increases or additional immunosuppressive agents may be required if there is no initial response. • Once symptoms improve to a mild level (ie, grade 1), corticosteroids are tapered off over 4 to 6 weeks. • Consider prescribing a PPI for gastrointestinal prophylaxis during corticosteroid therapy. • For long-term immunosuppression (>30 mg prednisone for more than 3 weeks), consider PCP prophylaxis. • Monitor for AEs associated with corticosteroid therapy (eg, hyperglycemia, edema, anxiety, iatrogenic adrenal insufficiency). Pearls on Use of Tocilizumab for CRS • Tocilizumab is approved only for CAR T-cell–induced CRS, not CRS mediated by other factors. • Hospitals and clinics that prescribe CAR T-cell therapies must be certified through REMS programs and have immediate, on-site access to tocilizumab. • For CRS, tocilizumab should be administered as an IV infusion only. • Consider storing tocilizumab vials in a separate location from prefilled syringes that are intended for subcutaneous administration to reduce the risk for dispensing errors. • Through inhibition of IL-6, tocilizumab can induce cytochrome P450 activities, which can persist for several weeks after a dose; therefore, concomitant medications should be reviewed for potential monitoring or dose adjustments. • Patients with concomitant neurologic toxicity also will need corticosteroids, since tocilizumab has limited efficacy in treating neurologic symptoms.

ICPi, immune checkpoint inhibitor; irAEs, immune-related adverse events; PD-1/PD-L1, programmed death (ligand)-1; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis

AEs, adverse events; CAR, chimeric antigen receptor; CRS, cytokine release syndrome; IL-6, interleukin-6; PCP, Pneumocystis jirovecii prophylaxis; PPI, proton pump inhibitor; REMS, Risk Evaluation and Mitigation Strategies

Based on references 13 and 18.

Based on references 1, 3, 4, 13, 15, 18, 25, and 30.

Guidance on grading and more specific management, including high-grade irAEs, can be found in the ASCO guideline.

Clinical

Pharmacy Practice News • December 2020

Review Article with CAR T-cell therapies must have 2 vials of tocilizumab on hand as part of the REMS program. Table 3 contains some key educational pearls for pharmacists about the use of corticosteroids and tocilizumab for irAE management.1,3,4,13,15,18,25,30 In the setting of the COVID-19 pandemic, additional challenges have arisen in balancing the risks and benefits of starting or continuing immunotherapeutic agents in cancer patients.21,31 Delivery of these agents requires contact with the health care system, and it is not known whether receipt of these agents affects the risk for contracting COVID-19 or its clinical course. For example, with FDA approval, extended-interval dosing strategies for checkpoint inhibitors (eg, pembrolizumab every 6 week administration) may be considered to limit patient exposure to health care environments.32 For CAR T- cell therapies, it may be prudent to delay treatment if resources such as hospital and ICU capacity and tocilizumab availability are strained.31 However, delaying treatment may not be realistic for many patients who need these therapies.21,33 Treatment decisions should be Individualized and consider indications and therapy goals. It is important to keep patients who are starting or continuing treatment informed of potential risks and the need to promptly report any symptoms of cough, fever, or dyspnea. Use of telemedicine also may help minimize exposure.34 Regulations for telemedicine have been relaxed through federal packages, notably the Coronavirus Aid, Relief, and Economic Security Act that expanded Medicare telehealth coverage. Several private payors also have expanded coverage of telemedicine as well. Given these expansions, pharmacists can contribute by encouraging telemedicine when appropriate and following up with patients to ensure that they have the knowledge and resources needed to navigate their health care during this pandemic.

COVID-19 pandemic in particular. Early identification and prompt management reduce patient morbidity and mortality. The complexities of cancer treatment with immunotherapies make a multidisciplinary approach increasingly important, with pharmacists playing an integral role in optimizing the management of patients treated with these agents.

References 1.

Dushenkov A, Jungsuwadee P. Chimeric antigen receptor T-cell therapy: foundational

science and clinical knowledge for pharmacy practice. J Oncol Pharm Pract. 2019;25(5):1217-1225. 2. Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016;39(1):98-106. 3. Yescarta [package insert]. El Segundo, CA: Kite Pharma Inc; 2020. 4. Kymriah [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018. 5. Yervoy [package insert]. Princeton, NJ: Bristol-Myers Squibb Co; 2020. 6. Libtayo [package insert]. Regeneron Pharmaceuticals Inc; 2020.

Bristol-Myers Squibb Co; 2020. 8. Keytruda [package insert]. Whitehouse Station, NJ: Merck Sharpe & Dohme Corp; 2020. 9. Tecentriq [package insert]. South San Francisco, CA: Genentech Inc; 2020. 10. Bavencio [package insert]. Rockland, MD: EMB Serono Inc; 2020. 11. Imfinzi [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals; 2020. 12. Tecartus [package insert]. Santa Monica, CA: Kite Pharma Inc; 2020. 13. Management of immunotherapy-related toxicities. Version 2.2019. National Comprehensive Cancer Network website.

7. Opdivo [package insert]. Princeton, NJ:

see IMMUNOTHERAPY, page 16

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Conclusion The use of immunotherapeutic agents has increased dramatically over the past few years with the approval of additional agents and expansion of indications.14 Thus, it is likely that more health care providers, including those in emergency medicine, will encounter patients with irAEs. Ultimately, timely recognition of irAEs and CRS is critical in managing the potential toxicities of immune checkpoint inhibitors and CAR T-cell therapies, respectively.35 Patients should be educated to promptly report any symptoms of cough, fever, and dyspnea during the

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16 Operations & Management

Pharmacy Practice News • December 2020

Finance

‘Our process allows for easy adaptation to other ambulatory care models and expansion to multiple medical specialties.’

A Win for Biosimilars Team continued from page 1

culprits. Such attitudes were due to “a lack of specialty care team education and support,” said lead author Jae Chau, PharmD, Kaiser Permanente Washington’s pharmacy clinical coordinator. To close that knowledge gap, the Clinical Pharmacy Administration Department developed a model incorporating multiple specialty care team members—prescribers, nurses, clinical pharmacists and infusion staff—to drive an integrated approach to communications with patients about biosimilar availability. “Training was provided to explain workflows and discuss best practices based upon previous experience,” Chau said. “We provided patient handouts and provider FAQs to all specialty team

members to aid in discussion of similarities and differences of the biosimilar product during patient outreach. All providers were educated about biosimilars, including an evidence summary to highlight the clinical trials used for FDA approval and those published after, such as observational cohorts. We found that our specialists were not resistant to biosimilar conversions—or starting de novo—but wanted to ensure patients would be allowed to switch back to the reference product, should there be an adverse drug reaction.” In 2019, this integrated approach was used for multiple “mini-launches” involving biosimilars bevacizumab-awwb (Mvasi, Amgen), trastuzumab-anns

More Biosimilars on Web Practical Considerations for Implementation of Biosimilars in Oncology: The Pharmacist’s Role, Parts 1-3 By Douglas Hackneyos, PharmD, BCOP Access under the Review Articles tab at pharmacypracticenews.com

IMMUNOTHERAPY continued from page 15

www.nccn.org/professionals/physician_gls/ pdf/immunotherapy.pdf. Updated December 16, 2019. Accessed August 3, 2020. 14. Hryniewicki AT, Wang C, Shatsky RA, et al. Management of immune checkpoint inhibitor toxicities: a review and clinical guideline for emergency physicians. J Emerg Med. 2018;55(4):489-502. 15. Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer. 2017;5(1):95. 16. Davies M, Duffield EA. Safety of checkpoint inhibitors for cancer treatment: strategies for patient monitoring and management of immune-mediated adverse events. Immunotargets Ther. 2017;6:51-71. 17. El Majzoub I, Qdaisat A, Thein KZ, et al. Adverse effects of immune checkpoint therapy in cancer patients visiting the emergency department of a comprehensive cancer center. Ann Emerg Med. 2019;73(1):79-87. 18. Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy:

American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2018;36(17):1714-1768. 19. Russano M, Citarella F, Napolitano A, et al. COVID-19 pneumonia and immunerelated pneumonitis: critical issues on dif-ferential diagnosis, potential interactions, and management. Expert Opin Biol Ther. 2020;1-5. doi: 10.1080/14712598.2020.1789097 20. Burke RM, Killerby ME, Newton S, et al. Symptom profiles of a convenience sample of patients with COVID-19 — United States, January–April 2020. MMWR Morb Mortal Wkly Rep. 2020;69(28):904–908. 21. Rossi E, Schinzari G, Tortora G. Pneumonitis from immune checkpoint inhibitors and COVID-19: current concern in cancer treatment. J Immunother Cancer. 2020;8(2):e000952. 22. FDA. Approved risk evaluation and mitigation strategies. Yescarta (axicabtagen ciloleucel) ) and Tecartus (brexucabtagene autoleucel). www. accessdata.fda.gov/Scripts/Cder/Rems/ index.cfm?event=IndvRemsDetails. page&REMS=375. Updated July 24, 2020. Accessed August 3, 2020. 23. Novartis. Kymriah (tisagenlecleucel) suspension for IV infusion. Risk evaluation and mitigation strategy (REMS): cytokine release syndrome and neurological toxicities. www.accessdata. fda.gov/drugsatfda_docs/rems/

—Jae Chau, PharmD (Kanjinti, Amgen) and rituximab-abbs (Truxima, Teva). “Often, we introduced the topic of biosimilars during an infusion of an innovator, or in the immediate period prior to the next infusion,” Chau said. “We used materials about biosimilars from the FDA and in-house handouts that we developed. These were made available to patients via mailing and could also be printed and shared during visits.” As of August 2019, 0% of patients were being treated with rituximababbs, 55.8% with bevacizumab-awwb, and 4.3% with trastuzumab-anns, Chau reported. By July 2020, those percentages had reached 90.7%, 98.2% and 83.3%. “Our process allows for easy adaptation to other ambulatory care models and expansion to multiple medical specialties,” Chau said. “As biosimilar availability continues to expand, using the entire care team, including clinical pharmacists, is pivotal for future biosimilar conversion success.”

Addressing a Perception Gap Miranda Kozlicki, PharmD, a PGY-1 resident practicing in the inflammatory bowel disease program at Vanderbilt University Medical Center, in Nashville, Tenn., which has a strong program of integrating pharmacists into specialty clinics, praised the multidisciplinary approach. “There is a perception gap

Kymriah_2018_05_01_Live%20Trainng%20 Program%20Slides.pdf. April 2018. Accessed August 3, 2020. 24. Baymon DE, Boyer EW. Chimeric antigen receptor T-cell toxicity. Curr Opin Pediatr. 2019;31(2):251-255. 25. Actemra [package insert]. South San Francisco, CA: Genentech Inc; 2020. 26. Le RQ, Li L, Yuan W, et al. FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome. Oncologist. 2018;23(8):943-947. 27. MacDougall K. The pharmacist’s role in educating the health-care team about adverse effects of immune checkpoint inhibitors. American Society of Clinical Oncology website. www.ascopost.com/ issues/may-25-2018/pharmacist-role-ineducating-the-health-care-team/. Published May 25, 2018. Accessed August 3, 2020. 28. Wood LS, Moldawer NP, Lewis C. Immune checkpoint inhibitor therapy: key principles when educating patients. Clin J Oncol Nurs. 2019;23(3):271-280. 29. Bosworth T. Tapering protocols needed to manage checkpoint inhibitor AEs. www. clinicaloncology.com/Current-Practice/ Article/05-18/Tapering-ProtocolsNeeded-To-Manage-Checkpoint-InhibitorAEs-/48704. Published May 16, 2018. Accessed August 3, 2020. 30. Postow MA, Sidlow R, Hellmann MD.

with biosimilars among patients about what they are, what they do, and how they affect the disease state,” she said in an interview. “The more times you hear the message, the better. Talking with the prescriber, the nurse and the pharmacist can improve knowledge and allow the patient to ask more questions that can help them feel comfortable with the decision to move forward with biosimilars.” When discussing a proposed switch from an originator such as infliximab to any of the biosimilars on the market, Vanderbilt does not use patient handouts like the ones offered by Kaiser Permanente Washington, but Kozlicki said they could definitely improve the process of patient education. “Having user-friendly materials that patients can take home clearly is beneficial, because if they just start Googling ‘biosimilars,’ it will be very confusing,” she said. “With biosimilars, there is always concern about the ‘nocebo effect,’ where the patient believes that they may receive less benefit than with the originator drug. Just by having these conversations, we can help prevent that from happening and patients should have better outcomes.” —Gina Shaw The sources reported no relevant financial relationships.

Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378(2):158-168. 31. Bachanova V, Bishop MR, Dahi P. Chimeric antigen receptor T cell therapy during the COVID-19 pandemic. Biol Blood Marrow Transplant. 2020;26(7):1239-1246. 32. Sehgal K, Costa DB, Rangachari D. Extended-interval dosing strategy of immune checkpoint inhibitors in lung cancer: will it outlast the COVID-19 pandemic? Front Oncol. 2020;10:1193. 33. COVID-19 patient care information - cancer treatment & supportive care. American Society of Clinical Oncology website. www. asco.org/asco-coronavirus-resources/careindividuals-cancer-during-covid-19/cancertreatment-supportive-care. Updated July 23, 2020. Accessed August 3, 2020. 34. Royce TJ, Sanoff HK, Rewari A. Telemedicine for cancer care in the time of COVID-19 [published online ahead of print July 16, 2020]. JAMA Oncol. doi: 10.1001/ jamaoncol.2020.2684 35. Renna CE, Dow EN, Bergsbaken JJ, et al. Expansion of pharmacist clinical services to optimize the management of immune checkpoint inhibitor toxicities. J Oncol Pharm Pract. 2019;25(4):954-960.

Dr Spencer reported no relevant financial relationships.

Operations & Management

Pharmacy Practice News • December 2020

Sterile Compounding

Navigating 503A and 503B Not for the Faint of Heart D

uring the Visante Business of Pharmacy Virtual Forum 2020, a topic that stirred considerable discussion was how to stay clear of the financial and regulatory pitfalls of sterile compounding. Whether a health care system operates as a traditional 503A compounder, focusing solely on patient-specific prescriptions, or is considering a 503B build-out to serve multiple facilities within its network, major variables need to be considered.

approach is not for the faint of heart. Ryan Stice, PharmD, the vice president of pharmacy at Sutter Health, headquartered in Sacramento, Calif., noted that, given the pressures of drug shortages, quality assurance and steadily rising costs, “it’s harder to sell not doing something versus taking action.” To that end, he and his colleagues did some research, and “it looked like we had a great 503B opportunity. But then we did a deeper dive and realized that it only

Brown, who was not part of the forum but described his system’s compounding strategies in a video interview with Pharmacy Practice News (bit.ly/3foioik). Most of Duke’s compounding is done as a 503A, but it is building a new facility that will have the capability of complying with 503B compounding requirements. For health systems considering such an approach, “the first step is to determine the CSPs you need most, what your volumes would be, and your highest-cost

‘For health systems that handle CSPs in ways that may be perceived as blurring the line between [503A and 503B] compounding, … [the 1-mile rule] puts them at risk of heightened scrutiny by regulatory agencies.’ —Fred Massoomi, PharmD One looming policy roadblock that came up is the question of when the FDA will implement its draft 1-mile radius provision, which allows 503A hospital pharmacies to distribute its compounded sterile products (CSPs) to owned and controlled health care facilities, as long as they are located within a 1-mile radius. The “1-mile rule,” as it’s known, was first released in draft form as part of the FDA’s 2016 compounding guidance. The provision is based on the reasoning that a centralized hospital pharmacy sending compounded drugs beyond a 1-mile radius would be operating like a 503B pharmacy but not regulated as one. In an April 2020 guidance establishing temporary policies regarding the compounding of certain drugs during the COVID-19 pandemic, the FDA made it clear that the 1-mile rule was still in draft form and would not be enforced yet. Fred Massoomi, PharmD, a senior director at Visante and a facilitator at the forum, said he expected a final version of the 1-mile rule to come out by the end of the year. Regardless of how that process plays out, he emphasized that health systems need to consider how the provision might affect their compounding operations. Indeed, “some states already have incorporated similar limitations into their statutes,” Massoomi said. “For health systems that handle CSPs in ways that may be perceived as blurring the line between the two compounding models, [the 1-mile rule] puts them at risk of heightened scrutiny by regulatory agencies.”

Still Scary: DIY 503B Building your own 503B facility is another fraught sterile compounding topic that came up during the forum. Based on comments made by several forum participants, taking that DIY

made sense to insource about 10 CSPs, and so we decided it just wasn’t a smart move, based on volume and value.” The question of value can be difficult to answer, noted one forum participant from a health system that submitted an application to be an FDA-registered 503B facility in May 2019. “If we had approached this simply from a cost-justification basis—we invested about $10 million—there is no way this would have been a viable operation,” said the forum participant, a chief pharmacy officer, who requested anonymity due to corporate communication policy. “We had to build other services into our centralized service center [CSC] for this to really work.” Adding those other services “was part of our overall strategy of building a viable CSC, rather than a partial solution to 503B compounding,” the participant stressed. “A CSC strategy that includes a 503B has an ROI [return on investment] that is much more attainable.” John Fanikos, PharmD, the executive director of pharmacy at Brigham and Women’s Hospital, in Boston, agreed that an integrated services approach to 503B is the key to success. “Contracting and supply chain distribution initiatives, nuclear medicine consolidation, code tray fulfillment—whatever service line you need to add in order to leverage that centralized facility is the way to make the investment work,” Fanikos said.

Making the Decision Hospitals should consider a few key factors when deciding whether to build a 503B facility, noted Matthew Brown, PharmD, the pharmacy manager - compounding pharmacy at Duke University Health System Raleigh-Durham, in North Carolina. Duke is one of the few health systems to produce CSPs from active pharmaceutical ingredients (APIs), noted

items,” Brown said. “Then you need to determine how to produce those products. If it’s a simple, sterile repackage, it may be feasible to do that in a small CGMP [Current Good Manufacturing Practice] facility. If you have more complicated products (such as epidurals) that are going to

require the use of APIs, it gets much more expensive, because you’ll need to build larger cleanrooms with more complex and expensive equipment.” Brown emphasized that when going the 503B route, “every step in your compounding processes needs to be validated. The more complex the compounding process is, the more it’s going to cost for you to validate them.” Standard operating procedures (SOPs) are another hurdle. “There’s SOPs for syringe filling, SOPs for garbing of your compounding staff, and a host of other process-based SOPs, not to mention all of the quality assurance SOPs you’ll need to validate your compounding equipment and processes. “It is a different world,” Brown added. “On some level, you have to forget pharmacy and learn CGMP. Clearly, this is not something that is going to make sense for every health system.” —David Bronstein The sources reported no relevant financial relationships other than their employment.

18 Operations & Management

Pharmacy Practice News • December 2020

Specialty Pharmacy

HOSP Coalition continued from page 1

The new advocacy group is taking off at a critical time for health-system specialty pharmacies, as the market for costly specialty medications continues to outpace that of traditional medicines. In 2019, for example, specialty drug expenditures increased nearly 12% versus less than 1% growth for traditional pharmaceuticals, according to Doug Long, the vice president of industry relations at IQVIA. For 2020, that number is estimated to climb even further: Segal Consulting estimated that by the end of this year, the cost trend for specialty drugs is projected to increase by 15% (bwnews.pr/3p2ba8f ). That growth, however, does not guarantee access. Patients often are forced to join a preferred pharmacy to receive their medications, moving them away from the integrated patient care model offered by hospitals, according to HOSP. “Health-system–owned specialty pharmacies [offer] an important care integration strategy that helps to improve medication adherence, reduce readmissions and lower overall health care costs,” Tom Scully, a general partner at Welsh, Carson, Anderson and Stowe, and the former Centers for Medicare & Medicaid Services administrator, said in a statement. “HOSP delivers a platform for the industry to firmly establish the integrated specialty model as the new industry standard.” Scully also noted that the organization was “long overdue” and “a great way to share ideas and expertise, discuss databased research on improved outcomes,

and advocate” for the common interests of integrated specialty pharmacies.

Increased Advocacy and Focus Tim Affeldt, PharmD, the vice president for Specialty/Infusion Pharmacy Operations at Fairview Health Services and a member of HOSP’s board of directors, stated that creating a trade association “dedicated to representing specialty pharmacies owned by health systems means HOSP members can focus on our unique issues and commitment to patients and their care team. This is why Fairview has been very interested in HOSP from the beginning.” Other members of the new coalition include Baystate Health, Berkshire Health Systems, CommonSpirit Specialty Pharmacy, Hartford HealthCare, Shields Health Solutions, UMass Memorial Health Care and WVU Medicine. Baystate Health is typical of the integrated health systems that make up the alliance’s eight-member core group. It serves some 800,000 patients across western New England; and, according to Gary Kerr, PharmD, MBA, the chief pharmacy officer, it treats more than 30,000 patients per year through its

specialty pharmacy platform. “We need more collective weight,” Kerr said. “We need more stories to tell. Internally, we all agree that the more outcomes we can track, report and publicize, the better off we’re going to be.” Kerr cited a three-year retrospective cohort study by investigators from UMass Memorial Health Care and Shields Health Solutions, two other founding HOSP members, which suggested substantial potential savings in total medical expenditures (TME) among members of an accountable care organization (ACO) who used an integrated specialty pharmacy. The study, conducted at the UMass Memorial Medicare ACO, indicated TME savings of as much as $1,000 per month for integrated specialty pharmacy users compared with a control group of ACO patients who did not use the specialty pharmacy (JAMA Netw Open 2020;3[10]:e2018772). (Costs were calculated on a per-member per-month basis.) That is the kind of evidence, Kerr noted, that “spreads the impact story” of integrated specialty pharmacy “beyond just capturing scripts and filling and processing the claims.”

‘Who Better Than Us?’ Like its HOSP partners, Baystate Health strives to promote the value of its specialty pharmacy services to patients

‘We need more collective weight … [and] more stories to tell. Internally, we all agree that the more outcomes we can track, report and publicize, the better off we’re going to be.’ —Gary Kerr, PharmD, MBA

Helping you deliver better medicine to more people. Leiters is an FDA registered and inspected 503B outsourcing provider of high-quality compounded sterile preparations and services including: Pre-ﬁlled syringes, IV bags and vials

Specialty

Traditional pharmaceuticals

+12%

+<1%

with complex, rare and chronic medical conditions. “Here in Western Massachusetts, we service the ZIP codes within our immediate catchment area,” Kerr said. “Who better to service these patients than us?” Kerr questioned why some specialty products have to be shipped “from Texas or Florida or even other parts of New England when we’re exceptionally well set up to serve our patients.” He added: “We can do so much when we control all elements of the care model. It’s very difficult to give up control to outside parties and rely on the airlines and conventional courier services to get product [on time].” The Baystate Regional Cancer Program’s D’Amour Center for Cancer Care is a prime example, he said, of how shipment delays can affect patient care. Patients “are scheduled on particular days and intervals,” Kerr noted. “Their diseases are closely monitored. To have to rely on another specialty pharmacy provider outside the state is introducing all kinds of variables that we control when we own the channel ourselves.” Kerr said Baystate had made inroads into limited drug distribution channels. “Once we jump through fiery hoops and swim flooded tunnels, we’re able to get into the network,” he said. Will an organization like HOSP help to expand entry into those networks? “That’s our core belief,” Kerr said.

What About Excelera?

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Fairview’s Affeldt acknowledged that the HOSP Alliance isn’t the only effort to band health system specialty pharmacy stakeholders together. In fact, his hospital was a founding member of another group, Excelera, that seeks strength in numbers via its own network of providers. Asked to compare the

Operations & Management

Pharmacy Practice News • December 2020

Creating a trade association ‘dedicated to representing specialty pharmacies owned by health systems means HOSP members can focus on our unique issues and commitment to patients and their care team.’

—Tim Affeldt, PharmD

two organizations, Affeldt said although they share a common focus on providing integrated specialty pharmacy care, their operating models are completely different. “Excelera is a for-profit company that helps health systems start, operate and optimize specialty pharmacies,” he explained. HOSP, in contrast, is a nonprofit trade association that “is not going to help anyone start a pharmacy; they’re not going to help their membership run their operations.” Affeldt said he first heard about HOSP “a couple of years ago when Jack Shields [the founder and chairman of Shields Health Solutions] began talking about the possibility of a trade association that speaks for health systems that own specialty pharmacies. That was the genesis.” Affeldt said Fairview has long been a strong advocate for the belief that patients “do better” when their specialty pharmacy care is integrated within a health system. “So when HOSP was being formed,” he said, “we felt we shouldn’t miss out on that. We should be a part of that voice nationally.” Now a member of the HOSP board of directors, Affeldt said he envisioned the organization holding its first membership meeting “maybe a year from now— depending on COVID-19.”

What 1 of the Big 4 Has to Offer Despite health systems’ inroads into specialty pharmacy, the four largest providers in the market—CVS Specialty, Express Scripts’ Accredo, AllianceRx Walgreens Prime and Optum Specialty— continue to hold the dominant share. A common quality that these providers often cite in their success is a strong focus on the patient—a strength that Joel Wright, the CEO of AllianceRx Walgreens Prime, expanded on for Pharmacy Practice News. “Our specialty pharmacy patients benefit in a number of ways,” Wright said. “First, they have greater access to specialty and limited distribution drugs, thanks to our long-term and trusted relationships with pharmaceutical manufacturers.” Those manufacturers, he noted, “choose AllianceRx Walgreens Prime as a limited distribution drug partner because they value our ability to support patients throughout their treatment journey. Our trusted relationship with payors also helps ensure appropriateness of care for patients and reduces waste, all of which help keep health care more affordable. “Second, we continually provide innovative solutions to help patients manage

their health care on their own terms. This year alone, we launched several online disease state assessments empowering patients to manage their prescriptions.” Wright also cited AllianceRx Walgreens Prime’s partnership with Inovalon. “With Inovalon’s DataStream, AllianceRx

Walgreens Prime team members who serve patients can see real-time, patientspecific data from across the health care ecosystem,” he said. “These supplemental data offers our pharmacists greater insight into comorbidities, past and ongoing medications, laboratory results,

Specialty Pharmacy and other pertinent information.” The DataStream technology, Wright added, provides “a continuity in care between the patient, provider and pharmacy. Having access to information beyond our walls better informs pharmacy decisions and provides our specialty patients with improved treatment, holistic care and better outcomes.” —Bruce Buckley The sources reported no relevant financial relationships other than their employment.

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20 Operations & Management

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FDA Watch

2020: Truly the Year Of the Specialty Drug F

or years, specialty drugs have dominated new drug approvals, and 2020 was no different. Despite being distracted by a pandemic, the FDA is expected to come close to tying the 2018 record, when 39 novel specialty drugs were approved. This year also might be the one when the specialty spend outpaces the spend for traditional medications, according to Aimee Tharaldson, PharmD, a senior clinical pharmacist, emerging therapeutics, at Express Scripts. Last year, specialty drugs accounted for about 48% of the drug spend, and it’s been inching up, according to the “Express Scripts 2019 Drug Trend Report” (bit.ly/3kO36EN). “In the past 10 years, there’s been a significant number of new options to treat patients with several specialty conditions,” Tharaldson said at the AMCP Nexus 2020 Virtual meeting, where she highlighted several that were approved this year.

Cancer

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Cancer medications dominate the field. “In many cases, cancers are treated more as a chronic condition. So the number of people living with cancer is growing,” Tharaldson said. “Even though there was a dip in cancer drug approvals last year with only 11, we’re having a spike this year.” By the end of 2020, the FDA is expected to approve 21 novel cancer drugs, she noted. The agency started the year by approving avapritinib (Ayvakit, Blueprint Medicines), a once-daily tyrosine kinase inhibitor (TKI) indicated for gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha exon 18 mutation. “Clinical trials showed ... almost 85% of patients experiencing tumor shrinkage with this targeted drug,” said Richard Pazdur, MD, the director of the FDA’s Oncology Center of Excellence. About 5,000 patients in the United States are diagnosed with GIST each year, “and approximately 10% have GIST caused by a mutation, which makes the cancer more aggressive and difficult to treat,” Tharaldson said. Ripretinib (Qinlock, Deciphere), an oral TKI for the fourth-line treatment of advanced GIST, also was approved this year. Other specialty cancer drugs approved in 2020 were tazemetostat (Tazverik, Epizyme), an oral dimethyltransferase inhibitor for inoperable epithelioid sarcoma, and isatuximab-irfc (Sarclisa, Sanofi), an IV drug for relapsed/refractory multiple myeloma. “Epithelioid sarcomas are soft

tissue tumors, with only about 150 new cases diagnosed per year in the U.S.,” Tharaldson n said. The approval was based on a single arm of a multicenter trial in patients with histologically confirmed metastatic or locally advanced epithelioid sarcoma. Patients received tazemetostat twice daily until disease progression or unacceptable toxicity. The overall response rate (ORR) for 62 evaluated patients was 15% (95% CI, 7%-26%), with 1.6% having a complete response (CR) and 13% a partial response (PR); responses lasting six months or longer occurred in 67%. Isatuximab-irfc was approved as an IV infusion given once weekly for four weeks, then every other week. The biologic is used with pomalidomide and dexamethasone (pom-dex) to treat adults with multiple myeloma who have received at least two prior therapies. Isatuximab-irfc binds to the CD38 receptor on multiple myeloma cells. In the ICARIA-MM study, isatuximab-irfc plus pom-dex demonstrated a statistically significant improvement in progressionfree survival (PFS), with a median PFS of 11.53 months compared with 6.47 months with pom-dex alone (hazard ratio, 0.596; 95% CI, 0.44-0.81; P=0.0010). Tucatinib (Tukysa, Seattle Genetics) was approved with trastuzumab and capecitabine (Xeloda, Genentech) to treat patients with advanced HER2-positive breast cancer, including those with brain metastases, after failing at least one prior HER2 regimen. “Approximately 280,000 cases of invasive breast cancer are diagnosed annually and 17% overexpress HER2 protein,” Tharaldson said. In approving tucatinib, an oral TKI, the FDA considered the results of the HER2CLIMB trial, a randomized, double-blind, placebo-controlled trial of 612 patients with HER2-positive, unresectable, locally advanced or metastatic breast cancer despite treatment (N Engl J Med 2020;382:597-609). The median PFS in patients who received tucatinib plus trastuzumab-capecitabine was 7.8 months compared with 5.6 months for placebo. “It was particularly effective in patients with brain metastases,” she said. Sacituzumab govitecan-hziy (Trodelvy, Immunomedics), an antibody drug conjugate for the third-line treatment of metastatic triple-negative breast cancer (TNBC), was another noteworthy oncology drug approval, Tharaldson said. Of the 280,000 cases of breast cancer diagnosed each year in the United States, 10% to 15% are triple-negative. “Chemotherapy has been the mainstay

Operations & Management

Pharmacy Practice News • December 2020

FDA Watch Orphan Drugs

of treatment for triple-negative breast cancer,” the FDA’s Pazdur said. “The approval of Trodelvy represents a new targeted therapy for patients living with this aggressive malignancy.” The FDA approved sacituzumab govitecan-hziy based on a clinical trial of 108 patients with metastatic TNBC who had received at least two prior treatments for metastatic disease. The ORR was 33.3%, with a median duration of response (DOR) of 7.7 months. Of the patients with a response to sacituzumab govitecan-hziy, 55.6% maintained their response for six or more months and 16.7% maintained their response for 12 or more months. Sacituzumab govitecan-hziy also received orphan drug status in October, to treat glioblastoma.

A First for Cholangiocarcinoma Pemigatinib (Pemazyre, Incyte) is an oral fibroblast growth factor receptor 2 (FGFR2) indicated to treat cholangiocarcinoma that has spread and cannot be resected. Between 9% and 14% of the 8,000 cases diagnosed each year have FGFR2 mutations. “This is the first drug approved to treat this condition, which is typically treated with surgery and chemotherapy,” Tharaldson said. The FDA approval was based on data from a multicenter, open-label, single-arm study of 107 adults harboring FGFR2 fusions or rearrangements. Pemigatinib monotherapy resulted in an ORR of 36% and a DOR of 9.1 months. Capmatinib (Tabrecta, Novartis) is an oral TKI approved for adults with metastatic or inoperable non-small cell lung cancer (NSCLC) with a mesenchymal-epithelial transition (MET) exon 14 skipping mutation. Novartis estimated that up to 5,000 patients will be candidates annually for this treatment, which is the first drug to be approved for NSCLC caused by the MET mutation. The approval of capmatinib is based on results from the pivotal GEOMETRY study. In the MET exon 14 population (n=97), the confirmed ORR was 68% (95% CI, 48%-84%) and 41% (95% CI, 29%-53%) among treatment-naive (n=28) and previously treated patients (n=69), respectively. The study also demonstrated a median DOR of 12.6 months (95% CI, 5.525.3 months) in treatment-naive patients (19 responders) and 9.7 months (95% CI, 5.5-13 months) in previously treated patients (28 responders).

Another drug approved for NSCLS is selpercatinib (Retevmo, Loxo Oncology), an oral RET inhibitor, indicated for patients with RET-positive forms of the cancer. The drug also is approved for RET-positive thyroid cancer and competes with pralsetinib (Gavreto, Blueprint Medicines), another oral RET inhibitor that was approved in September. The treatment of small cell lung cancer (SCLC) also advanced in 2020 with the approval of lurbinectedin (Zepzelca, Jazz/PharmaMar), an alkylating agent that is infused every 21 days. The approval was based on data from a multicenter single-arm study in 105 adult platinum-sensitive and -resistant patients with SCLC who had disease progression after treatment with platinum-based chemotherapy. The data showed that in patients with relapsed cancer, lurbinectedin demonstrated an ORR of 35% and a median DOR of 5.3 months (30%) (Lancet Oncol 2020;21[5]:645-654). Brexucabtagene autoleucel (Tecartus, Kite/Gilead), a chimeric antigen receptor T-cell therapy, was approved as a one-time infusion for mantle cell lymphoma (MCL), and tafasitamab-cxix (Monjuvi, MorphoSys/Incyte) was approved as an IV infusion for large B-cell lymphoma. Tafasitamab-cxix should be used with lenalidomide and given on days 1 and 15 of a 28-day cycle after induction therapy. A rare form of non-Hodgkin lymphoma, MCL arises from cells in the “mantle zone” of the lymph node and predominantly affects older men. MCL is highly aggressive following relapse, with many patients progressing following therapy. The approval was based on the ongoing single-arm, open-label ZUMA-2 trial. Of 74 patients with relapsed or refractory MCL in the ZUMA-2 trial, 87% responded to a single infusion. “Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” said ZUMA-2 lead investigator Michael Wang, MD, a professor in the Department of Lymphoma and Myeloma at the University of Texas MD Anderson Cancer Center, in Houston. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.” Early clinical evidence indicates durable remissions in later lines of therapy, Wang added.

Several of the cancer drugs listed above also carry an FDA orphan drug abo designation. In fact, about 30% of candes cer drugs have an orphan drug designace ttion, indicating a therapy for a condittion that affects fewer than 200,000 people. Although cancer is a large part pe of the designation, orphan conditions are much broader and a key component of the specialty market. “When you look at the specialty pipeline, over half of novel drugs in development are for orphan conditions,” Tharaldson said. Outside of oncology, other drugs that received this designation include osilodrostat (Isturisa, Novartis), an oral cortisol synthesis inhibitor to treat adults with Cushing disease, who either cannot have or were not cured by pituitary surgery. Cushing disease affects about 4,000 U.S. patients annually. Patients with hemophilia A or B also will benefit from 2020 orphan drug approvals—particularly those who are prone to inhibitor formation, which can lead to treatment failure and bleeding episodes. Coagulation factor VIIa (recombinant)-jncw (Sevenfact, LFB S.A.) was approved to control episodes in patients with hemophilia A or B with inhibitors by bypassing the parts of the coagulation pathway that are blocked by inhibitors. It is given as an IV infusion every three hours until bleeding stops. The safety and efficacy of factor VIIa (recombinant)-jncw were evaluated in 27 patients with hemophilia A or B with inhibitors, which included treatment of 465 mild or moderate episodes and three severe bleeding episodes. The study assessed the efficacy of treatment 12 hours after the initial dose was given. The proportion of mild or moderate bleeding episodes treated successfully with both the lower dose of 75 mcg/kg and higher dose of 225 mcg/kg (requiring no further treatment for the bleeding episode, no administration of blood products, and no increase in pain beyond 12 hours from initial dose) was approximately 86%. The study also documented three severe bleeding episodes that were treated successfully with the higher dose. Another study of factor VIIa (recombinant)-jncw in 15 patients with severe hemophilia A or B with or without inhibitors found that two doses, 75 mcg/kg and 225 mcg/kg, were optimum. Tharaldson cited several other noteworthy orphan drugs: Inebilizumab-cdon (Ulpizna, Viela Bio) and satralizumab-mwge (Enspryng, Genentech), approved for adults with neuromyelitis optica spectrum disorder (NMOSD) who are AQP4 antibodypositive. NMOSD affects approximately 10,000 Americans, and 80% have the AQP4 antibodies. Inebilizumab-cdon is a biologic that is infused every six months, and satralizumab-mwge is an

interleukin-6 inhibitor given as a selfadministered subcutaneous injection once monthly. Triheptanoin (Dojolvi, Ultragenyx), a purified medium-chain triglyceride, is a source of calories and fatty acids for patients with long-chain fatty acid oxidation disorders, in which the body is unable to produce energy from fat. If left untreated, patients can have severe complications, including early death. Fostemsavir (Rukobia, ViiV Healthcare) is a novel oral glycoprotein 120 attachment inhibitor used with other antiretrovirals for the treatment of multidrug-resistant HIV, which affects about 10,000 U.S. patients. Approval was supported by a clinical trial showing that more than half of patients had undetectable viral loads with the addition of fostemsavir. Risdiplam (Evrysdi, Genentech), a survival of motor neuron 2 (SMN2) splicing modifier, was approved for the treatment of spinal muscular atrophy. About 500 U.S. infants are born with the disorder annually. Risdiplam is designed to treat this disorder caused by mutations in chromosome 5q that lead to SMN protein deficiency. In the FIREFISH and SUNFISH trials, risdiplam showed clinically meaningful improvements in motor function in people with varying ages and levels of disease severity. For instance, infants achieved the ability to sit without support for at least five seconds, a key motor milestone. Risdiplam also improved survival without permanent ventilation at 12 and 23 months old. A liquid medicine, risdiplam is administered daily at home by mouth or feeding tube. Viltolarsen (Viltepso, NS Pharma) is an antisense oligonucleotide to treat Duchenne muscular dystrophy for patients with a confirmed mutation, amenable to exon 53 skipping. About 8% of patients who have this dystrophy have a confirmed mutation amenable to exon 53 skipping. Somapacitan-beco (Sogroya, NovoNordisk), given as a subcutaneous injection, is a new, long-acting growth hormone analog for adults with growth hormone deficiency. Lonafarnib (Zokinvy, Eiger BioPharmaceuticals) was approved to reduce the risk for death from HutchinsonGilford progeria syndrome and for the treatment of certain processingdeficient progeroid laminopathies in patients aged 12 months and older. Progeria and progeroid laminopathies are ultra-rare, genetic, premature aging diseases that accelerate mortality in young patients. The disorders result from the buildup of defective progerin or progerin-like protein in cells. Lonafarnib, an oral farnesyltransferase inhibitor, helps prevent the accumulation of defective progerin or progerin-like protein. see NEW DRUGS, page 22

22 Operations & Management

Pharmacy Practice News • December 2020

FDA Watch

NEW DRUGS continued from page 21

In clinical trials, the life span of patients with Hutchinson-Gilford progeria syndrome who were treated with lonafarnib increased by an average of three months through the first three years of treatment, and by an average of 2.5 years through the maximum follow-up of 11 years. The investigators

reported an overall 60% reduction in mortality (P=0.0064).

Other Specialty Drugs Teprotumumab-trbw (Tepezza,Horizon Therapeutics) was the first drug approved for thyroid eye disease (Graves’ disease). Teprotumumab-trbw is given as an IV infusion every three weeks for eight doses. Ozanimod (Zeposia, Bristol Myers Squibb), a sphingosine 1-phosphate

receptor modulator, was approved for relapsing/remitting forms of multiple sclerosis. Peanut allergen (arachis hypogaea) powder-dnfp (Palforzia, Aimmune Therapeutics) is an oral immunotherapy to prevent severe allergic reactions, including anaphylaxis from accidental peanut exposure. Approximately 1.6 million children in this country have a peanut allergy, and 75% to 80% of these

allergies persist into adulthood. Decitabine and cedazuridine (Inqovi, Taiho Oncology) is used to treat certain patients with myelodysplastic syndromes. It is a fixed-dose combination of oral decitabine, which is an anti-metabolite that has been available as an injectable form for about 15 years, with a new cytidine deaminase inhibitor. —Marie Rosenthal

Table. 2020 Specialty and Traditional Novel Drug Approvals Brand Name

Active Ingredient

Veklury

Remdesivir

Gilead

Severe COVID-19

Inmazeb

Atoltivimab, maftivimab, and odesivimab-ebgn

Regeneron

Ebola virus

Gavreto

Pralsetinib

Blueprint Medicines

Non-small lung cancer

Detectnet

Copper Cu 64 dotatate injection

RadioMedix

Detect certain types of neuroendocrine tumors

Sogroya

Somapacitan-beco

Novo Nordisk

Growth hormone

Winlevi

Clascoterone

Cassiopea Spa

Acne

Enspryng

Satralizumab-mwge

Genentech

Neuromyelitis optica spectrum disorder

Viltepso

Viltolarsen

Nippon Shinyaku

Duchenne muscular dystrophy

Olinvyk

Oliceridine

Trevena

Acute pain in certain adults

Evrysdi

Risdiplam

Genentech

Spinal muscular atrophy

Lampit

Nifurtimox

Bayer Healthcare

Chagas disease in certain pediatric patients younger than 18 years of age

Blenrep

Belantamab mafodotin-blmf

GlaxoSmithKline

Multiple myeloma

Monjuvi

Tafasitamab-cxix

Morphosys US

Relapsed or refractory diffuse large B-cell lymphoma

Xeglyze

Abametapir

Dr. Reddy’s

Head lice

Company

Indication on Approval Date

Inqovi

Decitabine and cedazuridine

Otsuka

Adults with myelodysplastic syndromes

Rukobia

Fostemsavir

ViiV Healthcare

Resistant HIV

Byfavo

Remimazolam

Acacia

Sedation

Dojolvi

Triheptanoin

Ultragenyx Pharma

Molecularly long-chain fatty acid oxidation disorders Metastatic small cell lung cancer

Zepzelca

Lurbinectedin

Jazz

Uplizna

Inebilizumab-cdon

Viela Bio

Neuromyelitis optica spectrum disorder

Tauvid

Flortaucipir F18

Avid Radiopharmaceuticals

Diagnostic agent for patients with Alzheimer’s disease

Artesunate

Amivas

Severe malaria

Cerianna

Fluoroestradiol F18

Zionexa

Diagnostic imaging agent for certain patients with breast cancer

Qinlock

Ripretinib

Deciphera

To treat advanced gastrointestinal stromal tumors

Retevmo

Selpercatinib

Loxo Oncology

To treat lung and thyroid cancers

Tabrecta

Capmatinib

Novartis

Non-small cell lung cancer

Ongentys

Opicapone

Neurocrine

Patients with Parkinson’s disease experiencing “off” episodes

Trodelvy

Sacituzumab govitecan-hziy

Immunomedics

Adults with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease

Pemazyre

Pemigatinib

Incyte

Certain patients with cholangiocarcinoma, a rare form of cancer that forms in bile ducts

Tukysa

Tucatinib

Seattle Genetics

Advanced unresectable or metastatic HER2-positive breast cancer

Koselugo

Selumetinib

AstraZeneca

Neurofibromatosis type 1, a genetic disorder of the nervous system causing tumors to grow on nerves

Zeposia

Ozanimod

Celgene

Relapsing forms of multiple sclerosis

Isturisa

Osilodrostat

Recordati Rare

Adults with Cushing’s disease who either cannot undergo pituitary gland surgery or have undergone the surgery but still have the disease

Sarclisa

Isatuximab

Sanofi Aventis

Multiple myloma

Nurtec ODT Rimegepant

Biohaven

Migraines

Barhemsys

Amisulpride

Acacia

Prevent nausea and vomiting after surgery

Vyepti

Eptinezumab-jjmr

Lundbeck Seattle BioPharmaceuticals

Prevent migraine in adults

Nexletol

Bempedoic acid

Esperion

Adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of low-density lipoprotein cholesterol

Pizensy

Lactitol

Braintree Labs

Chronic idiopathic constipation in adults Epithelioid sarcoma

Tazverik

Tazemetostat

Epizyme

Tepezza

Teprotumumab-trbw

Horizon Therapeutics Thyroid eye disease Ireland

Ayvakit

Avapritinib

Blueprint Medicines

Adults with unresectable or metastatic gastrointestinal stromal tumor

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