The Medicare Part D Rebate Rule and Biosimilars

It will take a close reading of the 600 pages of government policy to grasp their implications, but it seems the final rules by the Department of Health and Human Services (HHS) could on one hand lower a real barrier to biosimilar uptake and on the other hand create real problems for biosimilar manufacturers. In this post, we’ll put the spotlight on the final Medicare part D rebate rule.

Started in 2018, Stopped in 2019, Started Again in 2020, Stopped in 2021?

In early 2019, HHS Secretary Alex Azar announced the administration’s proposal to remove the drug rebate safe harbor from the federal antikickback statute. And it was mentioned during the summary of 2018 as a way to help biosimilar competitiveness, as part of the Biosimilar Action Plan. We attributed this move as a way of addressing the drug rebate trap, which acts as a disincentive to utilize newly marketed biosimilars. Movement on the drug rebate safe harbor stalled once the federal government calculated that such a plan would increase Medicare premiums. Secretary Azar claims that this rule would have no effect on final premiums.  

Secretary Alex Azar

According to the final rule, the safe harbor for part D rebates will be revoked January 2022, if no measures are taken by the incoming Biden administration to delay, modify, or even eliminate the rule. Rebates or discounts offered to Medicare patients at the pharmacy counter or point of sale will still be permitted. The existing rules regarding Medicaid supplemental rebates and rebates to Medicaid managed care organizations are not affected by the new safe harbor policies.

In the original proposed rule, “As proposed, this safe harbor would protect reductions in price on prescription pharmaceutical products offered to plan sponsors under Medicare Part D, Medicaid MCOs, or through a PBM acting under contract with either if: (1) the reduction in price is set in advance; (2) the reduction in price does not involve a rebate, unless the full value of the price reduction is accomplished through chargebacks or is a rebate required by law; and (3) the reduction in price is completely reflected in the price the pharmacy charges to the beneficiary at the point of sale.”

Now if It Applied to Part B, Well That Would Be Big for Biosimilars…

The first biosimilars that will largely be reimbursed under the part D benefit will likely be the first insulins approved as biosimilars in 2021 or 2022, or adalimumab in January 2023. The others available today are covered under part B, with perhaps the occasional exception being pegfilgrastim prefilled syringes, which can be self-injected at home. The removal of drug rebates for part D drugs can be a positive for biosimilars, assuming they are covered under the pharmacy benefit. It will allow more direct price competition for these specific agents, but because it is limited to part D drugs, the ramifications of this rule for biosimilars will remain somewhat limited. Applying the rebate rule to part B drugs would be a much more effective way to increase utilization of biosimilars (both existing and future). To the extent that Medicare plans to eventually shift more drugs from part B to part D, this may apply to far more agents. Will the safe-harbor rebate removal apply to commercial plans? Not according to HHS: “Extension of the revised discount safe harbor…to the commercial market is beyond the scope of this rulemaking.”

If part D biosimilars competed on price alone rather than on price plus rebates, that would help level the drug formulary playing field. That is, if the rebate revenue received by PBMs and plans is now negated, those organizations would no longer have major incentives to prefer the reference product. The reason is simple: Rebates are only valuable if a drug is utilized. A biosimilar when launched has no utilization. Therefore, a biosimilar rebate is rendered meaningless when the reference drug has 100% utilization.

There is some concern that pharmacy benefit managers and others might attempt to retain current rebate revenue in some other form (perhaps as a chargeback for “value-based services”). In response, HHS specified, “We note that labeling an arrangement as ‘value-based’ does not necessarily make it so, and any arrangement (whether labeled as value-based or otherwise) must still comply with all conditions of a safe harbor” and that “Value-based arrangements, like all arrangements that implicate the anti-kickback statute, must be analyzed on a case-by-case basis.”

Some point-of-sale rebates used to assure preferred formulary positioning would still be protected by a safe harbor. The key is to pass those rebates onto consumers at the point of sale and not to a pharmacy benefit manager.

Deflating the Gross-to-Net Bubble

Of course, the biosimilar poster child for the damage posed by rebate traps is the long-running Inflectra® and Renflexis® vs. Remicade® story. Yet, this is the only real case where biosimilar uptake has been seriously damaged because of rebates offered by the reference manufacturer (Janssen Biotech). We have pointed out previously that Pfizer did themselves no favors in its initial pricing and launch of Inflectra, allowing Janssen to easily offer greater rebates to protect its marketshare.

Although the rebate itself may not be at fault, it allowed the gross-versus-net bubble to grow, to a point where retail prices had no bearing at all on actual cost. The infamous rebate has also clouded individual drug contracts to a point where no payer truly knows what another payer is paying for a drug product. Removing rebates from the equation can only make drug deals and discounting more transparent—unless or until PBMs and others find a new way to opacify the system.

As expected, the major trade organizations are lining up for or against the changes in the rebate safe harbor. The Pharmaceutical Care Management Association, representing PBMs, has stated its opposition. America’s Health Insurance Plans, an association representing payers, has expressed its concerns that lost rebate revenues will likely raise premiums. On the other hand, PhRMA has issued statements that support the rebate rule. Both BIO and PhRMA have published statements that are very much against the most-favored nations rule. BIO has gone so far as to call the latter an attempt at revenge by the Trump administration for the organization not fulfilling the President’s wish for a vaccine prior to the election.

In our next post, we’ll address how the Most Favored Nation’s Clause could be a very real disincentive to biosimilar makers.

Archigen Closes Its Doors After Failing to Introduce Rituximab Biosimilar

Samsung Biologics announced in its third quarter earnings report that they and partner Astra Zeneca have agreed to shut down their joint venture Archigen Biotech. This news was first reported in the Korea Biomedical Review.

Archigen was created in 2014 with the hope of developing a biosimilar to reference product Rituxan/MabThera for the treatment of follicular lymphoma. We profiled Archigen in 2018, and tried to update their clinical trial outcomes in May 2020, but did not receive a response. The handwriting may have been on the wall then.   

Its phase 3 trial of SAIT101 was completed in October 2020, and results can be viewed on This investigation of 316 patients with low-burden follicular lymphoma revealed week 28 overall response rates of 66.3% vs. 70.6% for the biosimilar and reference products, but a week 4 overall response rate of 59.6% and 70.0%, respectively. Complete response rates were equivalent at week 12 and 28 (25.0%–26.9% and 34.7%–35.2%, respectively). Partial response rates at week 12 were different, at 33.1% for SAIT101 and 45.9% for the reference product but similar at week 28 (32.4%–36.8%). P values were not provided for any of these differences.

In terms of immunogenicity, the appearance of antidrug antibodies did not appear to be different between the treatment groups over time. The incidence of neutropenia was higher in the biosimilar group (4.5% vs. 0.63%), infusion-related reactions were lower in the biosimilar group (11.5% vs. 16.5%), and headache was more common in those taking SAIT101 (5.7% vs. 1.3%). There appeared to be no other differences between the treatment groups.

It may be worth noting that Biogen is a partner with Roche in the manufacture of Rituxan. Biogen is also a 50% partner with Samsung Biologics in its Samsung Bioepis subsidiary (as well as a US marketing partner with Samsung Bioepis on its ophthalmologic biosimilars). This tangled web may have had something to do with the decision to stop work on SAIT101 and close down Archigen.

Pfizer’s Ruxience® began marketing in January of this year for the treatment of follicular lymphoma, and according to Bernstein Research, had captured more than 20% of the market after only 9 months.

Wraparound Services: Biosimilar Makers Must Be Sure to Get Them Right

Since 2014, when Zarxio® was the first biosimilar product approved by the Food and Drug Administration, manufacturers have seemed attuned to the need to two aspects of the launch: (1) pricing and (2) service offerings.

Payers, for example, assumed that the net cost of biosimilars would be lower than the reference product assumption (the question of how much lower was not yet known). They also assumed that biosimilar manufacturers would be prepared to come to market with a set of wraparound services (including “hub” services) that would be competitive with those offered by the reference manufacturer.

Specifically, we’re referring to amenities like patient access to financial assistance and education about the product, and physician-targeted services that might improve prescribing, administration, and ordering of the biologic or biosimilar. From the physician practice perspective, these services can speed prior authorization requests for the product. The reason is simple: If you want physicians to prescribe a biosimilar, it has to be as easy to prescribe as the reference agent; no physician practice wants additional administrative work.

Over the past 5 years, as 17 biosimilars entered the market, these manufacturers approached the wraparound services aspect as a cost of doing business, an aspect of gaining a level playing field. Some biosimilar makers touted their efforts, like Coherus CompleteTM to equal or surpass the reference manufacturer’s services.

For some companies, this package may be more easily bought than created. At last week’s GRx+Biosimilars 2020 virtual conference, Gary Deeb, Senior Vice President, Global Licensing Business Development for Lupin, believes that its wraparound services will not be developed organically. As a generic drug maker entering the biosimilar field, Lupin doesn’t currently offer these services on its individual generic drugs. Recognizing their criticality, Mr. Deeb said, “We’re not set up to offer these services seamlessly to physician offices. We have to adapt and need to understand the therapeutic space. And part B drugs are very different from part D drugs [Lupin usually provides] in terms of services.” He stated, “We may need to go to our partners for these services. We don’t have to do it internally. We just need to recognize that these services will be important.”

Just because a reference manufacturer provides a certain package of services, this does necessarily represent the bar one has to meet, asserted Paul Thomas, Chief Commercial Officer, US, Biocon Biologics. He believes that the wraparound service packages in play today may not be optimal, and perhaps may offer too broad a slate of services. Mr. Thomas said, “Some services are critical and required, others are less so. It’s about separating out what is core to helping the patient versus other services.”

Another factor that may change the equation on wraparound services is the potential for interchangeability, particularly that for insulin. If an interchangeable insulin is brought to the market, and the pharmacy makes the decision to substitute for it, what will be the pushback from providers or patients, if the hub services provided by the biosimilar manufacturer does not match up well with those of the reference drug maker? We won’t know the answer to this until it occurs. But it does sound like some companies, like Biocon, may be willing to test this question.

Samsung Bioepis’ Ranibizumab Biosimilar Application Filed With FDA

On November 18, Samsung Bioepis and its marketing partner Biogen jointly announced that the 351(k) application for SB11, a ranibizumab biosimilar, has been filed and accepted by the Food and Drug Administration.

The US patent for Roche’s reference product Lucentis® expired in June 2020, and the market for ranibizumab could be over $1 billion. Lucentis has losing market share for the treatment of retinal vascular disorders to aflibercept over the past few years.

Although second to file for approval, Samsung Bioepis’ most prominent competitor experienced a setback earlier this year. In its third-quarter earnings report, Coherus Biosciences disclosed that it was preparing for “Bioeq’s resubmission of a 351(k) BLA with the FDA for the biosimilar candidate to Lucentis (ranibizumab) in 2021.” Coherus had previously indicated that its licensing partner Bioeq had filed for FDA approval in late 2019 but did not disclose an application rejection or other negative result. That could leave the door open for Samsung Bioepis and Biogen to launch first. Only one other biosimilar manufacturer has publicly announced an intent to market a ranibizumab biosimilar.

In its press release, Hee Kyung Kim, Senior Vice President and Clinical Sciences Division and Regulatory Affairs Team Leader, Samsung Bioepis, stated. “If approved, SB11 will be a valuable treatment option for people with retinal vascular disorders, potentially helping millions of people in the United States.”

Ian Henshaw, Senior Vice President and Global Head of Biosimilars at Biogen, called the 351(k) filing for SB11 “a key milestone in the process for providing a new potential treatment option for patients in the United States with retinal vascular disorders.” A drug approval application was also filed with the European Medicines Agency in October. The timing of this filing could place the FDA decision date in the late third quarter to early fourth quarter of 2021.

Thoughts on the Savings From a Biosimilar Shared-Savings Model

Of the several pieces of legislation floating in the netherworld of Congressional action (or inaction) is the bill that was introduced by Senators John Cornyn (R-TX) and Michael Bennet (D-CO) early this past summer. Entitled the Increasing Access to Biosimilars Act of 2020, it directs the Centers for Medicare and Medicaid Innovation to create a shared-savings model for part B biosimilars. This proposal will likely be reintroduced next year, and a session at this week’s GRx+Biosimilars meeting delved into some of the forces behind it.

John O’Brien, PharmD, MPH

John O’Brien, PharmD, MPH, Managing Partner, South Capitol, said that when he served as advisor to the Secretary and Deputy Assistant Secretary for Health Policy at Health and Human Services, the department recognized that two major payment barriers existed for biosimilars. They were (1) rebate traps, “which will be really problematic for part D biosimilars when they exist” and (2) a misaligned incentive that pays doctors more for prescribing reference products than biosimilars. The use of rebates are ingrained in the system, he pointed out, and “as long as that profit motive exists for prescribers, it will be a challenge for biosimilars,” said Dr. O’Brien.

Jim Carey

Jim Carey, Executive Director, US Health Policy, Merck,added that most of the biosimilars are 15% to 35% lower by WAC when first introduced onto the market. “If providers begin to use biosimilars and share in those savings, the idea is that they will adapt their behavior. If there is no savings, there is no sharing.”

Since there is limited ability to address buy-and-bill medications from the health system perspective, a biosimilar shared-savings model has been suggested. In a previous article, we addressed this question from an administrative standpoint, as in: “Is it practical?” Dr. O’Brien emphasized that a potential shared-savings model to biosimilars would have to pass muster with actuaries at CMS. They will want to know whether the savings accrued will be worth the effort. Only then would CMMI be given the challenge of creating a demonstration project.

Dr. O’Brien cited a report from Milliman, indicating the savings from a biosimilar shared savings demonstration may not be huge. He stated that Milliman’s calculated accumulated savings by 2029 to the federal government will be $1.9 billion to $12.5 billion, while paying bonuses to physicians of $3.4 billion to $7.4 billion. This may be a close call. We were unable to find the Milliman analysis, so we cannot verify the assumptions on which it is based.

Mr. Carey noted that regardless of whether the shared-savings model is based on a fixed percentage of savings going back to the physician or on some other calculation, “we model significant savings to the system.” He stated that “the results of these economic models are not yet published but will be soon.”

The idea of shared savings for biosimilars seems as enticing as it does for general medical care. And Dr. O’Brien said, “The momentum for this type of approach is growing. Personnel is policy in the fed government.” In a new Biden administration (even without a Democratic majority in the Senate), he expects some Obama alumni to be part of it, and they were behind the push for biosimilar savings in the first place. “Even the folks who are there now, generally support policies like this,” he said.

In Other Biosimilar News…Samsung Bioepis released the one-year results of its phase 3 trial of SB11, a biosimilar of ranibizumab, at the American Academy of Ophthalmology 2020 virtual meeting. This study confirmed the interim results, which were reported in May 2020. “The 52-week data confirms SB11 has equivalence in efficacy and pharmacokinetics as well as a comparable safety and immunogenicity profile with the reference product,” stated Hee Kyung Kim, Senior Vice President, Samsung Bioepis in a press release. The biosimilar maker filed for approval with the European Medicines Agency in October, and an FDA filing on SB11 is expected in the next few months.

Employers Getting Their Arms Around Biosimilars, but Will Push Come to Shove?

Until the onset of COVID-19 pandemic, employers sponsored the health plans that covered 49.6% of the US population. “Although the situation is very fluid,” F. Randy Vogenberg, PhD, RPh, Board Chair of the Employer–Provider Interface Council (EPIC), told BR&R, “a conservative estimate is that this may have dropped closer to 40% at one point with the higher unemployment resulting from the country’s economic downturn.”

According to Bernstein Research estimates, currently marketed biosimilars are now saving the US about $5.6 billion a year, and employers are only now awakening to the promise of biosimilars. At this week’s Festival of Biologics virtual meeting, a voice representing employers asked for colleagues to go beyond understanding biosimilars and to help secure the sustainability of the industry.

Margaret Rehayem

Margaret Rehayem, Vice President of the National Alliance of Healthcare Purchaser Coalitions, told attendees that “employers hope that biosimilars will take a more competitive place in the market, and that “employers look for reduction of wasteful and low-value drugs.” That fits well the raison d’être for the introduction of biosimilars.

There does seem to be some impetus for moving these days: Ms. Rehayem said, “The biosimilar industry is not quite at the point of sustainability in the US. Employers are just now wrapping their arms around what a biosimilar is. They need now to engage.”

One might expect this engagement to start by pressing their health plan vendors to (1) prefer the use of biosimilars so they can see some of that annual savings and (2) ensure that any rebates are passed completely through to their own bottom lines (particularly self-insured companies). Ms. Rehayem concurred, stating that payers are still driving choices of reference vs biosimilars. “Employers have taken a back-of-the-bus approach,” she stated, “letting payers make coverage decisions and accepting their recommendations. But you almost have to have a medical degree to understand the issues.

“It is important though to look at how biosimilars first came on the market, with [small] discounts, making it easy for the reference manufacturers to compete,” she said. “Employers need to step up and engage beyond the use of intermediaries. More work needs to be done.” She called for more education, adding that the FDA’s approach on restricting misleading information was just a beginning.

“Some of our employer coalitions are acting on their own,” said Ms. Rehayem, pointing to a paper from the Midwest Business Coalition on Health, “which takes employers through a series of steps to take the right actions at the right time [to improve access to biosimilars]. Employers should be looking at contracts, looking at the status of formularies, moving from the back seat to

Physician Familiarity Fuels Infliximab Switches to Biosimilar

The results of an interesting study of infliximab biosimilar use at a Veterans Administration (VA) facility were announced at the Academy of Managed Care Pharmacy’s Nexus 2020 session. The paper outlined real-world experience that further bolsters support for biosimilar infliximab switching.  

The poster did not indicate industry support for the research. It detailed changes in coverage over time and subsequent uptake of the two marketed biosimilar versions of Remicade®. Before May 2017, the reference agent was considered the preferred infliximab agent on the VA National Formulary. After that date, the VA decided to make Inflectra® (Celltrion/Pfizer’s infliximab-dyyb) the preferred product. This policy was changed in September 2018, when Renflexis® (infliximab-abda) was designated the preferred infliximab agent.

Derek K. Pinnell, PharmD, and colleagues from the VA Medical Center in Salt Lake City noted that 10 months after the first policy change, Inflectra utilization rose above 50% of total infliximab prescriptions. However, Renflexis garnered more than 50% utilization only two months after being named preferred product. The reduced delay (and subsequent > 85% total utilization of Renflexis) was considered a consequence of “increasing familiarity and comfort with biosimilars in general,” stated the authors. They were quicker to institute biosimilar infliximab switches after that most recent policy change.

Unsurprisingly, fewer patients who were already established on treatment with the reference biologic switched to Inflectra than patients who were treatment naïve after the biosimilar was designated the preferred agent. There was more than a 20-point difference between infliximab-naïve use of Remicade and those who were already receiving it (65%) after the first policy change. This difference rapidly dropped once Renflexis was named preferred product (just 20% remained on the reference product at the end of the study period in December 2019).

It does seem that VA physicians were far quicker to switch to another biosimilar once the second policy change was implemented. This applied even to physicians with patients already receiving Remicade.

The study offers a glimpse of what can also occur in other health systems and provider networks. As contracting or pricing deals change over time for medications like infliximab, payers can be expected to change preferred status on one or more of the drugs in the category. It appears that physicians, at least in the VA system, are willing to roll with the changes.

Missed Opportunity for Huge Savings With Biosimilar Etanercept

Although it appears today that biosimilars for Enbrel® will not be launched before 2029, a budget impact analysis presented at the Academy of Managed Care Pharmacy (AMCP) Nexus meeting hints at how much money is being left on the table until then.

Researchers from Xcenda and Sandoz (the latter of which has an approved etanercept biosimilar) assessed the situation from the perspective of a US commercial 1 million member plan with a 3% annual growth rate. The price of the biosimilar was pegged to 15% below the 2020 wholesale average cost of the reference product. They addressed two potential scenarios for patients already receiving chronic therapy: (1) 5% uptake at baseline and 5% monthly increase in uptake (i.e., 60% marketshare by end of year 1) and (2) 5% baseline utilization and 7% monthly gains in marketshare (i.e., 82% by end of year 1). Marketshare increases in years 2 or 3 were not considered. For treatment naïve patients, a 12% baseline uptake and 5% monthly increase was assumed through year 1.

In scenario 1, a biosimilar etanercept would be administered to 1,077 patients compared with scenario 2, in which 1,453 patients would receive the biosimilar. After the first year, the total net cost savings with biosimilar etanercept amounted to nearly $6.5 million in scenario 1 and $8.6 million in scenario 2. By the end of year 3, annual savings (not cumulative savings) would grow to $12.8 million with 60% marketshare of the biosimilar or $17.2 million with 82% marketshare. Three-year savings might be as high as $42.4 million in scenario 2. Average cost savings per patient switched to the biosimilar from Enbrel would be $11,069 per year and $11,071 for the two scenarios, respectively.

Biosimillar etanercept savings
Scenario 2 savings

Whereas this budget impact model has several limitations, including potential double-counting of hypothetical members who have more than one inflammatory indication, it does offer insight into the possible value of biosimilars at a relatively modest discount (but a fairly aggressive switching schedule).

When asked about the effect of Enbrel price increases on model savings, Edward Li, PharmD, of Sandoz, told BR&R, “Our model was constructed earlier this year (April), and therefore the WAC pricing that we used is reflective of that time period. We did not account for price increases of the reference drug over time, because we cannot speculate what other companies will do. Therefore, this is the more conservative estimate of the savings; if there are indeed price increases, then the savings will be larger.”

Price increases from Amgen on this agent does seem highly probable. In the past, our own simple calculations of the impact of obstructed access to biosimilar discounts have resulted in distressing future numbers that illustrated not so much biosimilar etanercept savings but excess costs having been paid to reference manufacturers because of delayed marketing. If the 2029 date holds, giving Amgen 31 years of exclusivity on this agent, a 15% discount will be cold comfort: It may be considerably less paid by a health plan, but it won’t feel like savings at all.

Pharmacists Believe Lack of Interchangeability Information and Designations Pose Real Barrier to Biosimilar Adoption

How do payers and health systems view the barriers to biosimilar adoption in October 2020? A survey by the Academy of Managed Care Pharmacy (AMCP), the AMCP Foundation, and its partners revealed the latest views of a group of healthcare stakeholders.1

The poster presented at last week’s Academy of Managed Care Pharmacy’s (AMCP) Nexus meeting yielded preliminary data from the survey, demonstrating interesting trends on barriers to biosimilar adoption. The results of this survey offered a bit of a contrast to previous survey findings (which also included several groups of stakeholders, with pharmacists comprising nearly three-quarters of respondents).

In a 2018 study, researchers from AMCP found that the most likely strategies to advance biosimilar uptake, according to surveyed payers, involved federal and state policies, prescriber education on real-world studies, and explicit guidance from the FDA guidance on biosimilar substitution. For the 2020 study, several questions were modified and the pool of respondents did not replicate that in 2018. The researchers acknowledged that as a result, limited comparisons can be made between the two surveys. Yet, based on the 2020 study sample of more than 200 payers and health systems, it seems that priorities have shifted slightly (Table).

1. Expanded Medicare/Medicaid Policies1. Clear FDA Guidance on Interchangeability
2. Prescriber Education on Real-World Studies2. Interchangeability Studies
3. Formulary Policies that Promote Biosimilar Use in Treatment-Naïve Patients3. Formulary Policies that Promote Biosimilar Use in Treatment-Naïve Patients
4. Clear FDA Guidance on Substitution4. Medicaid/Medicare Policies to Encourage Biosimilar Use
5. Medicaid/Medicare Policies to Encourage Biosimilar Use5. Reduced Cost-Sharing for Patients Using Biosimilars

In the current study, the vast majority of 17 strategies specified by the researchers were considered useful in improving biosimilar adoption. Yet the emphasis seems to have moved subtly away from switching and towards interchangeability as the top strategy to improve biosimilar uptake. In 2018, aspects in interchangeability ranked only number 8, but just two years later, occupied the top 2 spots. Again, the comparability of these two surveys is very limited, so this statement would need to be considered with caution.

From a managed care policy perspective, the main attraction of interchangeability is that such a product can be automatically substituted at the pharmacy. From a practical standpoint, however, this is beginning to seem like a mirage that draws no closer.

The current, real-world situation is this: The concept of interchangeability is not directly applicable to a drug covered on the medical benefit, and essentially all biosimilars marketed today are covered under medical benefit (with the possible rare exception of pegfilgrastim prefilled syringes, which can be self-injected).

The first potential interchangeable product could be one of the adalimumab biosimilars, which will first be marketed in 2023. Yet, even if Boehringer-Ingelheim did receive the FDA designation, this would not guarantee that payers will prefer Cyltezo®. This agent will face competition from at least six other agents released throughout that year.

The research group reported that health plans and PBMs are considered most influential in improving biosimilar uptake, at 43% of respondents. “Employer groups, professional
associations and commercial manufacturers appear to be
least likely to be influential (<5% for each),” they stated.


  1. Chung I, White A, Spain J, et al. Overcoming biosimilar barriers: Stakeholder perspectives on strategies to overcome challenges—a cross-sectional study (poster). Presented at AMCP Nexus 2020, October 20–23, 2020.

Biosimilar Bytes from DIA Biosimilars 2020

The sessions from the Drug Information Association Biosimilars 2020 virtual meeting held earlier this month touched on some very important points for the biosimilar community. In addition to our previous meeting report, I thought some others needed to be mentioned briefly, with a bit of commentary.

One Biosimilar Class That Poses Difficulties for Comparative Pharmacokinetic Analysis  

Andrea Laslop, MD, Head of Scientific Office, Austrian Medicines and Medical Devices Agency (AGES), Austria, reminded that in consideration of efforts to streamline the biosimilar development and approval process, some biologics may require special considerations. She pointed to locally acting biologics like ranibizumab, aflibercept, and dornase alfa. When these agents are utilized, they result in “very low systemic levels, which makes a comparison of [pharmacokinetic] endpoints between the biosimilar and reference product very difficult.” She believes that pharmacodynamic endpoints in comparative studies may be used to compensate for this gap in the analytical data.

DIA Biosimilars 2020
Andrea Laslop, MD

Comment: Both ranibizumab and aflibercept, ophthalmologic agents, are undergoing active biosimilar development for the US market, and these prospective manufacturers generally have planned or are in the midst of phase 3 trials. For these next-wave biosimilars, the Food and Drug Administration (FDA) may decide to weigh the phase 3 trial results a bit more heavily than for other systemic biosimilars, just for this reason.

Countering Negative Anecdotal Biosimilar Reports

Ali McBride, PharmD, MS, BCOP, Clinical Coordinator, University of Arizona Cancer Center and President of the Association of Community Cancer Centers, reminded attendees of the continued importance of biosimilar education. “I’m still hearing questions about why clinical studies haven’t occurred for extrapolated indications,” he said. Some of the negative information about biosimilars comes from small or anecdotal studies, according to Dr. McBride. We need to counter these reports with greater education: “Pharmacovigilance (including national registries and Medwatch reporting) will have a big role in addressing these one-off reports.”

Comment: Publication of any case studies or negative outcomes associated with biosimilars has been sparse, and certainly overwhelmed with information about successful switches, positive clinical trial results, and impressive cost savings. Dr. McBride is right, however, in that published pharmacovigilance data will help further establish the quality of biosimilars. Expect the BBCIC to be a greater player in this effort.

DIA Biosimilars 2020
Ali McBride, PharmD, MS

Workflow Challenges to Onboarding Biosimilars

Dr. McBride also covered the practical aspects of incorporating biosimilars into practice. He made an excellent point about the workflow challenges: “EMR implementation can actually be more difficult than obtaining P&T review!” Rya Haumschild, PharmD, MS, Director of Pharmaceutical Services at Emory Healthcare, agreed, “Updating the EMR is so important and time consuming when adding a biosimilar.” Dr. McBride pointed to the problem of incorrect order entry, which includes not only using the wrong drug name (though EMRs have done a good job of addressing the four-letter suffixes), as well as E-prescribing chargemaster elements, like dosing and drug quantity.

In the case of pegylated (long-acting) filgrastim, “every physician will refer to Neulasta® but very few will specifically designate OnPro®,” he said. This causes more issues for the finance department than it does for patient care (because they think all of these patients are receiving the prefilled syringe formulation). There is the separate issue of stocking multiple biosimilars based on different health plans’ formulary preferences.

Comment: Incorporating biosimilars into the everyday workflow of a practice is critical to smoothly increasing uptake of biosimilars. Yet, this topic is rarely covered in detail. It is good to hear that EMR vendors like EPIC have been meeting this challenge.

Role of Pharmacists in Biosimilar Education

DIA Biosimilars 2020
Shubha Bhat, PharmD, MS

Shubha Bhat, PharmD, MS, BCACP, Ambulatory Care Clinical Pharmacy Specialist—Gastroenterology, Center for Digestive Disorders and Crohn’s and Colitis Program, Boston Medical Center (BMC), described the BMC’s transition from Remicade® to Inflectra®, which was approved by the medical center’s P&T Committee in December 2017. Pharmacists were at the forefront of gaining the physician’s buy-in for the program, which included clinical monitoring of patient outcomes, switching to the biosimilar for patients whose conditions were stable for at least 6 months (or naïve to treatment). From March 2018 to June 2019, 97% of eligible patients were given the biosimilar. Only five patients did not transition to the biosimilar (discontinued infliximab treatment or lost to follow-up). Dr. Bhat noted, “None of the discontinuations were related to the biosimilar switch. Our real-time monitoring of patients revealed no differences in outcomes or safety.”

Comment: The pharmacist’s role in terms of drug information and biosimilar education cannot be overemphasized. Health systems and health plans have learned to rely on pharmacists to help ease any concerns prescribers may have regarding biosimilars. And not only P&T Committees but individual prescribing physicians need their expertise in transitioning programs like this one.

Orphan Biosimilars Pose Analytic Challenges

There is no guarantee of financial success when developing orphan biosimilars, and Dr. Laslop raised an additional practical issue that may raise the stakes further. Under current regulatory guidelines, clinical noninferiority studies of biosimilars generally that the biosimilar perform within 10% or 15% equivalency margins in terms of efficacy and safety. With some biologics to treat orphan diseases (like eculizumab or romiplostim), the number of available patients for study is much smaller than for rheumatoid arthritis or breast cancer, for example. Therefore, Dr. Laslop said, “The low number of patients precludes stringent equivalence margins and the development of a comprehensive safety database prelicensing.” This is a very good point and may mean that other (unspecified) statistical approaches in comparative trials may be more useful in the assessment of orphan biosimilar candidates.