In 2006, the European Union approved its first biosimilar drug. Now, more than a decade later, the United States and its FDA continues to struggle with how to incorporate these unique pharmaceutical treatments into mainstream medical practice. The complex and organic nature of these biological drugs makes it difficult to test and approve them in a traditional setting—biosimilar treatments will need to gain some degree of acceptance in at least 1 of 4 distinct medical and scientific communities before they can enter the mainstream. Physicians, pharmacists, patients, and health plans will play key roles in the eventual uptake of biosimilars by the broader marketplace, and each population must be reached in a very targeted way.

Perhaps the biggest obstacle to biosimilar uptake is the broad lack of familiarity with these medicines in most disciplines. For 

, despite the fact that biologic and biosimilar drugs have played a vital role in cancer treatment over the past decade in Europe, a 2011 survey of oncologists in found that about 1 in 4 doctors had never heard of biosimilar drugs and more than half admitted that they had “no or slight familiarity” with these treatments.

“People are not going to purchase or prescribe something they do not understand,” said Joseph P. Fuhr, Jr, PhD, professor emeritus at Widener University and member of The Center for Biosimilars editorial board.

“We have a lot of work to do on education,” added Molly Leber, PharmD, BCPS, FASHP, a manager of medication policy and formulary management in the Yale New Haven Health System who also serves on the editorial board at the Center for Biosimilars. “There are numerous surveys that have shown healthcare professionals and patients don’t know about the current drug approval process [for biologics] and even less about biosimilars.” Leber added that many healthcare professionals still have concerns about the safety of biosimilars because of the general lack of awareness about the approval process, and that patients often do not realize that there are alternatives to their current biologic therapies.

While the expanding presence of oncological biosimilars and biologics in the US marketplace will bring these drugs more to the forefront of the prescribing physician’s mind both in oncology and elsewhere, there are certainly some roadblocks to overcome before they become anything other than a last resort. Many physicians who are familiar with biosimilar and biologic drugs still tend toward prescribing more familiar treatment options because biosimilars feel risky; a biosimilar’s corresponding biologic often bears the full weight of testing and trials with the result that the “confirmatory trials” for biosimilar safety required by the FDA may feel inadequate. It is, in fact, the case that for biosimilars the weight of proof of safety and efficacy lies largely within the proof of similarity to a biologic. Further complicating the prescription process, because biosimilars are organic and their effects may evolve in a patient who takes them over time, physicians may be reluctant to prescribe a treatment that feels unpredictable to both the patient and themselves.

 Brian Lehman, MBA, MHA, RPh, manager of pharmacy benefits and policy in Columbus, Ohio, also on the editorial board for The Center for Biosimilars, described the oncology sector as one most likely to be impacted in the near term by biosimilar uptake. “The oncology community is currently impacted by the biosimilar Zarxio (filgrastim) that has been available on the market since September 2015,” he observed. Zarxio bolsters the immune system and helps a patient’s body overcome infection. Lehman further noted that there are 3 additional biosimilars in the oncology pipeline: those for Neupogen, Neulasta, and Procrit/Epogen. “The biosimilar pipeline is robust,” he said, adding, “the FDA has 66 biosimilar 

Furthermore, given that oncology drugs are “some of the highest-priced drugs available,” as Fuhr described them, the introduction of biosimilars will likely “increase access and improve quality of life for many patients,” he said.

In order to reach the prescribing population and generate momentum for biosimilar uptake in this sector, physicians must understand how valuable these drugs may be from both a treatment standpoint and an accessibility standpoint. While effective treatment is certainly vitally important, the relatively lower cost of biosimilar drugs will, of necessity, also play a role in their uptake. However, there is some debate about how affordable biosimilar drugs will actually be compared to their biologic counterparts. “Lower prices and greater access will benefit consumers and help decrease prices in the healthcare market,” observed Fuhr, adding that this will also motivate “innovators” to “attempt to find new drugs as profits on old drugs decline.”

Lehman agreed, stating, “The greatest benefit [of biosimilar uptake] would be increasing patient access to more affordable life-changing and even life-saving biologic drugs.”

Not all sources agree that biosimilar uptake will lead to more affordable treatments, however. Currently, biologic drugs account 

 about 62% of Medicare spending in the United States, compared to about one-third in 2005. It is to be hoped that biosimilar treatment options might make biologic results available to populations that either might not be able to afford them or that might not be prescribed to them first due to cost issues. This in itself presents another uptake issue, however, since conventional wisdom 

 that biosimilar drugs should cost about 30% less than their biologic counterparts but, thus far, these drugs are debuting at more of a 15% discount. This is due, in large part, to the costs of testing and proving similarity of these drugs.

Over the next 4 years, a large number of biologic patents will expire, expanding biosimilar development and production options. This could increase competition in the marketplace and drive biosimilar prices down to that benchmark 30% discount. If it does not, however, physicians and government bodies that fund many of their prescriptions will continue to find it difficult to prescribe these treatments when more conventional options exist.

Pharmacists and Biosimilar Interchangeability

Along with the prescribing community, pharmacists could play a major role in the uptake of biosimilar drugs that receive an FDA approval for interchangeability. For example, in Great Britain, the British Oncology Pharmacy Association (BOPA) has 

 a “welcome statement” to biosimilars that states, in part, that biosimilars can and should be used in place of more expensive biologic treatments when possible. For example, according to BOPA, Rituximab, a biologic used to treat non-Hodgkin’s lymphoma, currently costs the country’s National Health Services about $209 million each year. Medical economists speculate that a biosimilar to Rituximab could save what BOPA called a “significant” amount of money that could be “reinvested into innovation and patient services.” In the United States, a similar attitude from healthcare law- and policy-makers will play a huge role in whether or not pharmacists are willing, when possible, to prescribe a biosimilar in place of the reference biologic.

“The best-case scenario would be if biosimilars can be incorporated into the healthcare system the same way that generic drugs are,” said Leber, elaborating that this would enable biosimilars to create the cost-savings their proponents say will come with their uptake: through competition. She added, “If you look at the European experience, there has been a significant decrease in the drug cost and increase in prescription volume.” Lehman agreed, observing, “Ideally, biosimilars will provide significant savings relative to the cost of the reference product, but there is also a need to balance and monitor for the potential and unintended consequence of discouraging some manufacturers from bringing more biosimilar competition to the US market.”

At the end of the day, it may well be the patient population that is most receptive to biosimilars because their concerns are less complex than those of prescribers and pharmacists. In one particular biosimilar 

, researchers asked the question: “Would you use [this biosimilar] for your mother if she had ERBB2-positive breast cancer?” They concluded, “The answer should be ‘yes.’” The patient population will ultimately be concerned with 2 main issues regarding biosimilars: efficacy and affordability/accessibility. Manufacturers may opt to reach past physicians and pharmacists directly to the patient population in order to solicit requests from patients for these treatments and to smooth the prescription process for physicians. If patients requiring these treatments can be educated about their efficacy, safety, and affordability, then many roadblocks in other populations are likely to erode on their own.

“Patients need education in order to feel confident that a biosimilar is just as safe and effective as the reference product,” said Lehman, citing European 

 including “over 400 million patient days of safe and effective treatment using biosimilars since the first biosimilar was approved and marketed in 2006.”

 Although acceptance of biosimilars in the medical marketplace is largely an issue of educating the appropriate populations about biosimilar topics most relevant to them, there is one potential roadblock to uptake that is largely administrative yet possibly far more substantial than any other: 

. It is not accurate to equate biosimilars to generics in terms of their associated biologics, although it may be helpful to do so to a limited extent when attempting to educate the general public about them. Because biosimilars are not generics of biologics, however, they are difficult to name and track within the medical billing system. At present, when a drug enters the mainstream and physicians begin prescribing it, the long-term effects of that drug can, to a degree, be tracked through the medical billing system. Data in the system can be reviewed to examine effects on subpopulations of patients and potential problems and benefits may be identified. However, biosimilars cannot be named the same way as generics, which have names that link them back to the brand-name drug, and also have a four-letter suffix that, according to the FDA, has no meaning other than that it is unique to that specific biosimilar. This will prevent inadvertent substitutions and support safety monitoring, but it will dramatically complicate how the drugs are processed through medical billing and could inhibit prescribers’ and pharmacists’ willingness to promote biosimilar use. “Formulary decisions are going to be complex,” Leber warned.

If biosimilar uptake does not gain momentum in the next decade the entire biosimilar industry could be derailed. In the event that it is too expensive to bring these treatments to market and achieve uptake in the medical sector, manufacturers may opt to pursue other treatment models. Of course, runaway successes of biologics like Genentech’s 

 (omalizumab), a treatment for allergic asthma that became a blockbuster drug in 2014, could entice manufacturers to continue research and development as long as the biosimilar industry continues to evolve in the public eye and the view of the medical population.

Biosimilars are demonstrably safe, effective, and affordable relative to their biologic counterparts. Conveying that message to the various stakeholders: physicians, pharmacists, and patients, is the linchpin to biosimilar uptake in the United States in the next decade.

Who Will Influence Biosimilar Uptake: Physician, Pharmacist, Patient, or Payer?

Carole Ellis

As of today, March 23, 2020, the life sciences industry completes “the transition.” New categories of biologics will now be licensed via the biologics approval pathway under the Biologics Price Competition and Innovation Act (BPCIA). 

This transition occurs 10 years after the 2009 enactment of the BPCIA. During that interim, manufacturers of certain biologics approved and under review for approval were in limbo as to how their products and rights of exclusivity would be treated under the new policy.

 previously approved under section 505 of the Federal Food, Drug, and Cosmetic Act (FDC) will automatically be “deemed” biologics licensed under section 351 of the Public Health Service Act (PHS). Ultimately, these drugs will be categorized as biologics, subject to biosimilar and not generic competition.

Unfortunately, the original BPCIA statute did not provide instructions to the FDA on how to implement this change. Therefore, the FDA has taken certain steps to enact the transition via several proposed rules and the implementation of its 

The BAP was released in July 2018. The plan is in 2 sections. The first defines key areas in which the FDA wants to focus its regulatory efforts: improving clarity and efficiency of the biosimilar approval process, enhancing understanding through better public communications, and addressing anticompetitive practices.  

The second section is made up of key actions. These are steps that the FDA is either taking or planning to take to improve review processes, create information resources, upgrade guidance, and encourage public feedback. Many of these actions have already been initiated.

On February 21, 2020, the FDA released a 

 that goes into effect today. It amends the FDA’s regulatory definition of a biological product so that it is aligned with the BPCIA. “Under the final rule, the term 

means any alpha amino acid polymer with a specific defined sequence that is greater than 40 amino acids in size.” This is one of the final steps in the 10-year transition process. It opens the door for insulins to be approved via the biologics license application (BLA) pathway.  

Over 100 products that had been approved via new drug applications under the FDC now must be reviewed as BLAs under section 351 of the PHS. Drugs that will be transitioned include naturally occurring proteins such as hyaluronidase, human growth hormones, and menotropins.

The FDA is focusing on insulins and has made waves with the release of 

 The FDA indicated that switching studies may not be needed for a designation of interchangeable insulins if analytical assessments suggest high similarity between biosimilars and reference products. This could speed the arrival to market of the first interchangeable biosimilars in the United States for insulin.

The FDA has also released 2 question-and-answer documents that discuss the transition for 

. With the BAP and guidance, the FDA has signaled that they are moving forward with the transition as a means of introducing more affordable medicines into the healthcare system—specifically, by expanding the use of biosimilars.

As of today, the FDA has completed a 10-year process to bring a wider set of biologics under the biologics license pathway for approval.
 

New Rule: Transition to BLA Pathway Is Complete

Ron Lanton

The rapid growth of prescription drug costs continues to be a great concern in health care. The increasing use of specialty drugs, which includes biologics and totaled $360 billion in 2019, is one of the main drivers of prescription drug spending in the United States.

 Biologics, used as primary treatment for various cancers and other serious conditions, represented only 2% of all US prescriptions in 2017, yet accounted for 37% of net drug spending.

Given the vast amount of health care resources consumed by biologics, biosimilars are increasingly gaining attention as a viable option. As stakeholders evaluate biosimilars and their promised benefits, here’s a look at what biosimilars are bringing to health care today and the progress made so far.

No Longer a Theory: Cost Reductions and Increased Access

Even though the US biosimilar market is still in the early stages, promising signs are emerging demonstrating that biosimilars can bring value to health care. The theory behind biosimilars is that, much like generic drugs, they promote competition by competing with reference biologics on price. This leads to lower prices, increasing access to life-saving drugs with minimized financial toxicity for patients.

Because US biosimilars are in their infancy, there are many unanswered questions. However, significant price reductions in the European Union were documented when biosimilars entered the market.

 Price reductions for epoetins in 2015 following biosimilar competition were substantial: 25% to 29% in Scandinavia, 39% in France, and 55% in Germany. Price reductions for the reference biologic and biosimilar filgrastim after the 2015 launch of a filgrastim biosimilar ranged from 14% in France to 27% in Germany.

 Because of the differences in market conditions, pricing, and governmental policies, the European data do not predict exactly what might happen in the United States. However, they do suggest price reductions in the same drug class can be expected as biosimilars are launched.

When the United States finally created the regulatory framework for biosimilars in 2009, the Congressional Budget Office estimated the sales-weighted market average discount on biosimilars would be 20% to 25% relative to reference agents―a high bar to reach, but hopefully one that is attainable.

The first US biosimilar, a granulocyte colony-stimulating factor (G-CSF) filgrastim, finally became available in September 2016, and data are clearly demonstrating significant cost savings. For example, for the fourth quarter of 2017, the payment limit for biosimilar G-CSF filgrastim was 28% lower than for filgrastim, based on CMS payment limits of average sales price (ASP) plus 6%.

Similar results have been demonstrated across The US Oncology Network, a network of more than 1350 independent physicians who deliver value-based cancer care in the community setting. The ASP trend for G-CSF biosimilars over a 3-year period clearly shows substantial cost savings compared with the reference product, based on CMS data for the Oncology Care Model (Figure 1).

The declining ASP trend for G-CSF over this same 3-year period resulted in a progressive increment in savings.

If the results seen so far in the United States and Europe hold true, as more biosimilars enter the US market, price reductions in the same drug classes will happen. Examples of this are already emerging. Commercial payers and pharmacy benefit managers in the United States are leveraging the competition from the few biosimilars in the market to negotiate lower prices on biologics in the same class and, in some cases, prefer one product over another.

The potential for biosimilars to deliver cost savings appears to be significant. The 

 utilized 2016 sales data from a large selection of biologic drugs to project potential savings from biosimilars over a 10-year period, concluding “…biosimilars would lead to a $44 billion reduction in direct spending on biologic drugs from 2014 through 2024, or about 4% of total biologic spending over the same period, with a range of $13 billion to $66 billion.”

 The study noted the savings potential will be affected by various evolving features, such as payment rates, litigation, competition, and interchangeability.

In addition to cost savings, biosimilars add value through increased access for patients. According to the European data, a substantial increase in use of therapeutic biologics and biosimilars occurred when a biosimilar entered the market, with the increase being attributed to reduced costs driven by competition.

An analysis for the Biosimilars Council projected 1.2 million US patients could gain access to biologics by 2025 due to increasing biosimilar availability.

Based on the data, women, lower-income patients, and the elderly would benefit more than others, although all individuals with health insurance would profit by having more treatment options.

Many originator biologics will lose exclusivity over the next 5 years, generating projected savings of $78 billion as biosimilars enter the market.

 As several long-awaited therapeutic biosimilars for cancer finally launch, patients will have more treatment options and the potential for more affordable care. However, these benefits will be realized only if more stakeholders embrace biosimilars.

Progress so far has been slow. For instance, it has taken 5 years for the first US filgrastim biosimilar, Sandoz’s Zarxio, to achieve a 32% market share.

 Unfortunately, biosimilars do not take off quickly, mainly because displacing products that are firmly entrenched in the market is not easy (Figure 2).

Those of us involved in biosimilar development, including the Center for Biosimilars®, are collaborating and working hard to drive better education for all stakeholders, especially physicians, because they play a key role in recommending and prescribing biosimilars for their patients. There is much work to be done, as demonstrated by a recent physician survey in which 74% of respondents indicated “physician confidence” was one of the biggest barriers to biosimilar adoption.

 It will be critical to help providers understand the vital role biosimilars can play in achieving success with value-based care. Even in the face of declining ASPs, providers can succeed in the value-based world by utilizing biosimilars that hold down costs while increasing access.

Preparedness Can Overcome Operational Hurdles

Successfully integrating biosimilars into a cancer practice requires careful preparation. This is especially critical for the therapeutic biosimilars that are now emerging, because they impact virtually all aspects of the practice. Strategies must be defined to ensure the delivery of high-quality care and operational efficiency. Practices can begin by examining various biosimilar brands and then refining their choices. Technology and workflow tools should be modified to minimize errors, and processes should be developed for updating providers and staff as the biosimilar market evolves.

Operational excellence and clinician and patient confidence can be achieved by developing strategies that integrate biosimilars with each phase of the patient journey, including diagnosis and treatment selection, insurance authorization, patient education, treatment scheduling, treatment admixture, and finally, treatment administration. Careful planning and execution of each phase will ensure a seamless patient experience, resulting in satisfied patients and secure reimbursement. It also is critical to educate all staff, including prescribers, revenue cycle employees, nurses, pharmacists and admixture personnel, so they understand the role they play in delivering quality care when a biosimilar is involved.

With health care transitioning away from fee for service—style practice, the future looks bright for biosimilars. Because they can increase access and decrease costs, biosimilars are poised to play a vital role in value-based care. As patients take on an increasing share of rising health care costs, biosimilars may become a valuable tool in minimizing financial toxicity while maintaining quality of care and stretching limited health care dollars. With the advent of coronavirus disease 2019, stakeholders may enthusiastically embrace biosimilars as they pursue ways to curb costs. Empowering the value biosimilars bring to health care just might be a big part of the solution everyone is seeking.

1. Statista. Prescription drug expenditure in the United States from 1960 to 2020. Accessed June 15, 2020. 

https://www.statista.com/statistics/184914/prescription-drug-expenditures-in-the-us-since-1960

2. Roy A. Biologic Medicines: The biggest driver of rising drug prices. 

https://www.forbes.com/sites/theapothecary/2019/03/08/biologic-medicines-the-biggest-driver-of-rising-drug-prices/#553ba24918b0

3. Patel KB, Arantes LH, Tang WY, Fung S. The role of biosimilars in value-based oncology care. 

4. Mulcahy AW, Hlavka JP, Case SR. Biosimilar cost savings in the united states initial experience and future potential. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6075809/

5. Biosimilars in the United States: Providing more patients greater access to lifesaving medicines. The Biosimilars Council. 2017. Accessed June 15, 2020. 

http://biosimilarscouncil.org/wp-content/uploads/2019/03/Biosimilars-Council-Patient-Access-Study.pdf

6. McGowan S. 5 years of biosimilars in the US: what have we learned? 

. January 29, 2020. Accessed June 15, 2020. 

https://pharmaphorum.com/views-analysis-market-access/5-years-of-biosimilars-in-the-us-what-have-we-learned/

Biosimilars Bring Value to Health Care

Robert Rifkin, MD, FACP

Hillel P. Cohen, PhD, is executive director of scientific affairs at Sandoz, helping to explain the principles of biosimilars and biosimilar policies to the healthcare community, patient advocacy groups, and health authorities. He has published and given presentations in the areas of biosimilar education, switching, interchangeability, naming, and safety. Cohen led Sandoz in its efforts on the first biosimilar presentation (Zarxio) to an FDA advisory committee and participated in the Biosimilar User Fee Amendments of 2017 negotiations on behalf of industry. He is active in biosimilar trade associations and helped cofound the Biosimilars Forum, where he is currently cochair of the education committee. He is also a member of the education and regulatory committees of the Biosimilars Council, a division of the Association for Accessible Medicines.

Hillel P. Cohen, PhD

Patients see drug couponing as a way to lower or avoid cost sharing on brand-name prescription drugs. Payers view drug couponing as undercutting their pharmacy benefit design. Pharmaceutical companies see drug couponing as the key to greater sales, especially when they are in nonpreferred formulary positions (i.e., after generic competition is launched).

In a value-based pharmacy benefit design, the payer assigns medications that are highly effective, lower cost, or both to lower formulary tiers, to make them attractive to plan members. On the other hand, agents that are deemed to be of less value are placed in higher tiers, or even excluded from coverage. Simply, lower cost sharing means greater incentive to use and better sales for the industry. However, drug couponing, which is now ubiquitous, remove the patient incentive to use higher value drugs (and the disincentive to use lower value agents).

In the case of biosimilars versus originator medications, drug coupons offered by the manufacturer of Enbrel

, for example, actually make it less expensive for the patient to purchase the originator than the biosimilar, assuming a lower-copay biosimilar tier. That is, unless Sandoz, the maker of the approved etanercept biosimilar, matches Amgen’s couponing program. In that case, there would be incentive or disincentive for either product, from the patient’s perspective.

In dealing with couponing programs, payers have 3 options: (1) let things be and hope that if patients have little cost sharing perhaps adherence will improve overall, (2) ban the use of couponing by members (in other words, don’t allow network pharmacies to accept them), or (3) exclude from coverage any drug for which coupons are offered (this would be a lot of drugs today).

, couponing has boosted prescriptions for branded medications by greater than 60%. For the nation as a whole, every copayment coupon adds up to $120 million over the first 5 years after a generic drug is introduced. For the manufacturers of 85 medications that first faced generic competition between 2007 and 2010, couponing boosted spending anywhere from $700 million to $2.7 billion over a scenario in which couponing did not exist.

To preserve the value of biosimilars, payers will have to carefully mull their limited options. Excluding coverage of originator products that have copayment coupons may not be practical, because of the delicate situation regarding switching of biosimilars and lack of an interchangeable designation, especially for patients on established therapy. Banning the use of copayment coupons seems like a more reasonable option for payers, but one that may cost them members, particularly in today’s heated competitive market. 

Payers will have to carefully mull limited options.

Drug Couponing: Better or Worse for Biosimilars?

Stan R. Mehr

Rick Lozano is the Vice President of Biosimilars and Integrated Business Development for AmerisourceBergen. His responsibilities span across AmerisourceBergen, working with internal teams and manufacturer partners to create and manage innovative biosimilar and follow-on biologic manufacturer relationships. In addition to his leadership in biosimilars, Lozano leads the team connecting AmerisourceBergen’s manufacturer sourcing and commercialization capabilities across all types of products to expand existing manufacturer partnerships and forge new business development opportunities.

Rick Lozano

Christopher Mikson, MD, JD, is a partner in Mayer Brown's Washington, DC office, where he serves as leader of the firm’s FDA Regulatory practice and coleader of the healthcare practice. He focuses his practice on FDA regulatory matters and complex litigation and transactional matters in healthcare and the life sciences.

Christopher Mikson, MD, JD

As the coronavirus disease 2019 (COVID-19) pandemic spreads, it will continue to affect the biopharmaceutical industry. Biosimilars are no exception, and the effect on their uptake and adoption will be multifaceted. Here are several ways that biosimilars are most likely to be influenced by COVID-19:

Inaccessibility of healthcare providers (HCPs) and other medical decision-makers:

 currently, COVID-19 is setting the priorities for most HCPs and hospital decision-makers: take care of affected patients, navigate the evolving COVID-19 coverage and payment landscape, and maintain an adequate supply of beds and personal protective equipment. During this time, institutions may lack the bandwidth to continue to evaluate complex biosimilar-related decisions and may stick to the status quo, the reference product, or the existing preferred biosimilar product until the dust settles. This will slow down biosimilar uptake across the board. As providers defer to their status quo therapy options to avoid unnecessary disruption, uptake of the 8 therapeutic oncology biosimilars 

 in the United States so far may be particularly hard hit.

Repurposed contracting and promotional activities: 

although many regular account manager activities have been disrupted by social distancing measures, contracting can be conducted effectively via digital media. This is especially true for biosimilar manufacturers with existing relationships or customers interested in immediate cost-saving opportunities who are not yet preoccupied with managing COVID-19. Many financial decision-makers (pharmacy directors, medical directors) are postponing contracting discussions. Account managers can now focus on bringing accounts on board for biosimilars and leave “pull-through” sales activity for later. Also, manufacturers that are preparing to launch biosimilars during this quarter or the next may decide to postpone marketing or do a soft launch, which would entail supplying product, leveraging digital or nonpersonal channels, and contracting via tele-detailing. This could affect biosimilars such as Merck's trastuzumab and bevacizumab biosimilars, Ontruzant and SB8, respectively, which are lined up for launch over the next 2 quarters.

COVID-19 is causing a dramatic mismatch of supply and demand that manufacturers are struggling to forecast. On the supply side, manufacturing and supply chain processes in hubs such as China, India, and the United States are being disrupted due to global lockdowns. On the demand side, conflated factors make demand difficult to predict. On one hand, patients delay seeking treatment, particularly for less convenient administration methods such as infusions, which can lead to lower patient volume and overall demand. On the other hand, stockpiling and demand for subcutaneous or oral formulations may cause a spike in demand for certain products despite decreasing patient volume. In February 2020, the FDA 

 the first case of a shortage of a drug due to coronavirus. Although all manufacturers are working to mitigate the risk of supply shortages, biosimilar manufacturers that rely on facilities in Europe and Asia may be particularly at risk on the supply side (

Delays in biosimilar approvals and clinical trials: 

most clinical trials are likely to be delayed due to challenges managing protocols, deprioritization in favor of more immediate acute care needs, and patients’ inability to travel to appointments. Beyond the logistics and prioritization challenges, manufacturers run the risk of trial participants contracting the disease, which leads to 

 on how to manage clinical trials during the pandemic. All of the above-mentioned complicating factors are likely to undermine Prescription Drug User Fee Act/Biosimilar User Fee Amendments dates for biosimilars with approval decisions scheduled by the end of 2020 (

Increased budget pressure can accelerate postcrisis biosimilar usage: 

Without a doubt, the current situation is putting significant budget pressure on the health system, with many providers 

 copays, coinsurances, and out-of-pocket costs due to COVID-19. Although the broader impact on the economy and health system is still unclear, what is certain is that after the crisis, providers will actively look for ways to compensate for the extra expense they are incurring now, and it will be more important than ever for biosimilars to deliver on their promise to bring savings to the healthcare system. In the meantime, it will be important to monitor what manufacturers of reference products and biosimilars do to help support providers as this situation evolves.

There are additional aspects of the pandemic that will affect both biosimilars and reference products alike, such as ensuring safe supplies of medicine in patients’ homes as we all observe social distancing. Patients, either on their own or in consultation with their HCPs, may start to make adjustments to treatment regimens to allow for less time in the hospital or the clinic, especially when it comes to biologics that suppress their immunity, as also recommended by 

Such recommendations, along with the already limited infrastructure, overburdened healthcare system, and social distancing policies will create a very difficult environment for biologics and biosimilars businesses in the short and medium term. However, companies can think strategically about how to create opportunities from these difficult circumstances, such as leveraging virtual technology for contracting discussions, stressing cost savings with cash-strapped customers, and improving patient-support wraparound services. These will help them set the stage for success in a post—COVID-19 world.

At the end of the day, the priority for everyone right now is protecting health and safety. Although biosimilar adoption and evolution to new treatment paradigms may stall, we firmly believe that health and safety are foremost in mind for providers everywhere.

Christina Corridon, MPH, MBA, is a principal in ZS’s Boston office and leads the firm’s biosimilar vertical. Scott Kniaz, MBA, is a strategy insights and planning manager in ZS’s Washington, DC, office. Will Gatziolis, MBA, is an associate principal in ZS’s New York office. Ross Shahinian is a strategy insights and planning manager in ZS’s New York office. Sandeep Sangwan, MPharm, is a knowledge management consultant in ZS’s New Delhi office.  All are key leaders in the ZS biosimilar vertical.

The coronavirus disease 2019 (COVID-19) effect on the biosimilar industry will be deep and lasting, causing not just approval and launch delays but profound structural changes in how business is done.
 

COVID-19's Multifaceted Effect on Biosimilars

Scott Kniaz, MBA

Another study from Europe found that biosimilar etanercept was effective and well-tolerated in the majority of patients who switched from originator etanercept.

The study looked at Samsung Bioepis’ biosimilar, SB4, which is sold as Benepali in European countries. 

 have also found SB4 to work well for the majority of patients who switched from the originator etanercept, Enbrel. The anti-tumor necrosis factor (anti-TNF) inhibitor, is currently prescribed in the United States for rheumatoid arthritis (RA), juvenile idiopathic arthritis, psoriatic arthritis (PsA), ankylosing spondylitis, and plaque psoriasis.

An observational study conducted in Poland looked at patients being treated for RA, juvenile idiopathic arthritis, PsA, or ankylosing spondylitis, in which the originator etanercept replaced SB4.  

Etanercept was replaced with SB4 in 162 patients (Group 1), and in another 6 patients SB4 was the initial biologic used (Group 2). Efficacy and safety were assessed over a 6-month period.

The biosimilar was effective and well-tolerated in the majority of patients, however, for 24 patients in Group 1 (14.8%), returning to the originator was necessary due to loss of efficacy or adverse events.

Previous observational studies have found rates of discontinuing the biosimilar ranging from 2-14%. Specifically in this study:

9 patients experienced clinically confirmed loss of efficacy

9 patients reported subjective loss of efficacy

13 patients reported adverse events, the most common of which were headache and skin lesions.

Of the 24, returning to the originator reversed the loss of efficacy or resolved the adverse event. No adverse events were reported in the 6 patients for whom the biosimilar was the initial therapy (Group 2), and the biosimilar was effective in these patients.

The authors conclude that SB4 was effective and well-tolerated in most patients, but that further research is required to investigate the effects of switching patients between originators and biosimilars.

Felis-Giemza A, Chmurzy&#324;ska K, Na&#322;&#281;cz-Janik J, et al. Observational study of inflammatory arthritis treatment by etanercept originator switched to an etanercept biosimilar.

2019;57(5):257—263. doi:10.5114/reum.2019.89516.

The study follows others that have found that SB4 works well for the majority of patients who switched from the originator etanercept, Enbrel.

Another European Study Finds SB4 Tolerated by Most Patients

Peter Page

 that it has entered into a partnership agreement with Mylan to commercialize its proposed etanercept (Enbrel) biosimilar. The agreement authorizes Mylan to market the potential biosimilar in Europe, Australia, New Zealand, Latin America, Africa, and Asia.  

Etanercept is an anti—tumor necrosis factor (TNF) inhibitor indicated to treat rheumatoid arthritis (RA), plaque psoriasis, ankylosing spondylitis, and other autoimmune diseases. Enbrel generated $5.2 million in 

Vinita Gupta, CEO of Lupin commented on the collaboration, 

, “We are extremely pleased to announce this partnership as both Lupin and Mylan share a commitment to bring affordable and high-quality medicines to market, especially in areas of unmet need.” 

 that Mylan has developed with a pharmaceutical company to accelerate a biosimilar commercialization. In April 2018, Mylan entered a partnership with Fijifilm Kyowa Kirin Biologics to launch its adalimumab biosimilar, referencing Humira, in Europe. 

“The introduction of biosimilars is an important mechanism to help increase access to more affordable biologics treatments, and our industry-leading portfolio of 20 biosimilar products positions Mylan to be at the forefront of delivering those sales,” said Rajiv Malik, president of Mylan of the collaboration. 

The proposed etanercept biosimilar completed a phase 3 clinical trial in February 2018 with a successful outcome. The 52-week trial, which included more than 500 patients with RA in 11 countries, compared the efficacy and safety of the proposed biosimilar directly with the reference product. 

Under the terms of the agreement, Lupin will receive an upfront payment of $15 million as well as an equal share in net profits of the product. The potential biosimilar has been filed with the European Medicines Agency and Japanese regulatory 

, and is planned to be filed in other domains.  

Lupin recently announced that it has entered into a partnership agreement with Mylan to commercialize its proposed etanercept (Enbrel) biosimilar.

Authors