Coronavirus disease 2019 (COVID-19) altered the workflow in all areas of the health care and life sciences industries. The FDA was not exempt from pandemic-induced upheaval. Meetings of advisory committees, which provide the FDA with expert advice on scientific, technical, and policy matters, were often postponed, and although drugs were still reviewed and approved, significant delays occurred.

From the start of the United States’ response to the COVID-19 pandemic in March 2020 until late summer, 2 biosimilars were 

: Hulio (adalimumab) and Nyvepria (pegfilgrastim). This represented not only an improvement in patient access and affordability of life-changing medications, but also a slowdown in biosimilar approvals.

In previous years, biosimilar approvals had steadily increased. As shown in the figure, the projected trend suggested approximately 12 biosimilar approvals for 2020 and 14 for 2021.

The trend line for biosimilar approvals suggested 2020 would be another strong year for the emergence of these lower-cost therapies; however, just 2 had been approved by the midyear point.

Although other factors came into play, such as patent expirations and product development, it appeared unlikely that the total of 12 biosimilar approvals would be achieved in the final quarter of 2020, and there was even potential for this slower pace to extend into 2021.

There were other reasons why patient access did not improve as expected. Typically, once manufacturers receive biosimilar approval, many face 

 that delay products from reaching the market promptly. These court cases often are purposely filed to interfere with market access to a new product. In some cases, “

” agreements postpone market entry of a biosimilar for many 

The COVID-19 crisis extended these delays because court systems temporarily closed to prevent spread of the virus and reopenings were late or occurred only in stages. Well into 2020, virus hot spots 

 to stall judiciary system operations, adding to the time needed to achieve market access for these new therapy options.

In addition to regulatory and judicial barriers, the overwhelming workflow within health systems also played a role in limiting access to new therapies. When health care facilities are in crisis mode, many components of the reimbursement and education processes, each of which is vital for biosimilar uptake, are hindered. 

Pharmacy and therapeutics (P&T) committees are necessary for ensuring new therapies will be included in the health care facility formulary. From the start of COVID-19, P&T meetings were often conducted virtually or 

 on evaluating emerging therapies for COVID-19 treatment, leaving little time for consideration of other formulary additions. With so much focus on COVID-19, little time was allocated to much else.

Within hospitals, the same was true regarding in-service education for physicians. With a need to educate physicians on current protocol, diagnostics, and treatment surrounding COVID-19, there was not much time left to educate on biosimilar therapies and novel agents.

“Lunch and learn” programs were likely on hiatus during the pandemic due to social distancing requirements, understaffing, and a strain on funding. Gathering professionals into a conference room could not be prioritized over keeping everyone safe.

Typically, many facilities partner with manufacturers to supply marketing materials and food to lunch and learns, and a clinical staff member presents on the topic at hand. As manufacturer field teams were grounded, less information reached the health care providers. Most nonessential visits were prohibited to prevent unnecessary risk of virus spread. These grounded professionals included sales representatives who provide information about new products, field reimbursement specialists who assist in getting products approved by the health plans, and medical science liaisons who can discuss new products on a higher level. These professionals were not as physically active as the pandemic unfolded and virtual methods of interaction were implemented.

If new therapies, including biosimilars, were not approved by the FDA, litigated promptly in the courts, cleared for formulary placement, or explained to physicians, it is unlikely patients were learning much about them. Especially when it comes to biosimilars, patients need to be aware of their potential options and the associated benefit of cost savings. With COVID-19, the nation entered a time of financial instability and loss of health care coverage, and these new therapy options became even more important for safe and affordable health care.

Coronavirus disease 2019 altered the workflow in all areas of the health care and life sciences industries, and the FDA was not exempt from pandemic-induced upheaval.

The Pandemic's Multilevel Effect on Patient Access

Amanda DeMarzo, PharmD, MBA, PACS, is the associate director of Patient Access with the National Board of Prior Authorization Specialists, an affiliate of the Accreditation Council for Medical Affairs, based in Oradell, New Jersey. She focuses on how to improve the current health care system as a whole through improved training, widespread certification, and advanced technology for better patient outcomes. She developed a passion for patient-centered care and shared decision making during patient-facing roles over the last 8 years.

Amanda DeMarzo, PharmD, MBA, PACS

Christina Mattia

Gregory Schimizzi, MD, is a co-convener of the Biologics Prescribers Collaborative (BPC) and the cofounder of Carolina Arthritis Associates, PA, in Wilmington, NC.  He has been a licensed and board-certified rheumatologist in private practice for 30 years. He co-founded, and previously served as president, of the Coalition for State Rheumatology Organizations (CSRO). He has also previously served as president, and a member of the executive board, at the North Carolina Rheumatology Association. Dr Schimizzi completed his undergraduate and medical school studies at Wayne State University in Detroit and completed his fellowship training at the University of California at Irvine.

Gregory Schimizzi, MD

CfB: I'm Tony Hagen with The Center for Biosimilars. Today, we're speaking with Sean McGowan. He's the senior director of Biosimilars for AmerisourceBergen. Welcome, Sean.

CfB: Sean, can you comment about biosimilar approvals in 2021? It was a pretty interesting year, I think, even though we had just a few.

McGowan: Yeah, it was it was quite a year of firsts for biosimilars in 2021. And in starting with the biggest approval and launch onto the market with the Semglee [insulin glargine] product from Mylan/Viatris. In July of 2021, the FDA approved the first ever interchangeable biosimilar product in Semglee, an insulin product indicated for treatment for type 1 and type 2 diabetes. That product launched in November with actually 2 versions of branded and an unbranded version. So, Semglee's entrance into the retail pharmacy, including mail order pharmacy, space makes it the first biosimilar to be covered under patients’ pharmacy benefit or Part D plans. So, kind of a first of its kind.

And the interesting thing about the Semglee launch is that it's got the potential to positively impact millions of more patients with its availability at the pharmacy counter. And this is definitely going to be a preview of what's to come with the future of Part D biosimilar launches. Not to mention that Semglee has been recently adopted on to a couple of national PBM [pharmacy benefit manager] formularies, including Express Scripts and Prime Therapeutics.

As we look into other therapeutic areas in 2021, we also saw the first biosimilar approval in the retina-ophthalmology space with Biogen's Byooviz, which references Lucentis [originator ranibizumab]. In October, we saw the FDA approved Cyltezo, making it the first interchangeable biosimilar product referencing Humira [originator adalimumab] and only the second interchangeable product ever to be approved by the FDA. And just to clarify, Cyltezo already had FDA approval. It was that interchangeable designation that received approval back in October.

Then in late December, right before the end of the year, the FDA approved 2 other biosimilars: an insulin glargine product from Lilly and then Yusimry, a biosimilar referencing Humira from Coherus [Biosciences]. So, all of these approvals and entrances in 2021 indicate to me that the FDA is getting back on track to reviewing and approving these products so patients can access these treatments. Also, it's an indication that the market continues to expand.

CfB: Just a footnote to that introduction. The Semglee launch was both a branded and unbranded. Can you shed any light on why that strategy was chosen by Biocon?

McGowan: Yeah, so Mylan and Viatris are the commercial partners and US Biocon is the manufacturing partner and from what I can see and what's been published publicly is that there's actually a non-biosimilar version of Semglee already on the market that had launched back in [the] summer of 2020. And that product came out on the market with a heavily discounted WAC [wholesale acquisition cost] price and looked to be launched to compete more in the Medicare Part D and Medicaid space or those cash paying patients. And then as the biosimilar products were being approved, Mylan/Viatris was looking to compete both in the commercial space as well as that Medicare/Medicaid space. And so, they've kind of launched the same product under 2 different names, 1 branded and 1 un-branded to fit specifically into some specific payer markets. And so, we're less than a quarter into the launch of this product and time will tell on how that strategy actually plays out.

CfB: Thanks. So, at the GRxBiosims meeting, which is a fairly informative conference, there were several FDA representatives speaking and they seemed a lot more focused on biosimilars than they had been in the past. Coming out of the pandemic, or at least, maybe partway through the pandemic, what does this signify, do you think?

McGowan: Yeah, it was great to see the quality and safety of generic and biosimilar medicines was a top priority for our industry and a key theme of the meeting. So, I'd say this progress is motivating and moving in the right direction. The FDA has also promised to provide more clarity on the handling of the interchangeable designation, which I think everyone is really interested to gain some additional clarity and insight into that designation, as we see more and more products receive that designation in the future. It's also encouraging that the pharmacy benefit managers have been moving interchangeable biosimilars onto their preferred formularies like they've done with Semglee and that pharmacists in the retail space now get a chance to experience a biosimilar product. But overall, there's still a lot of basic education required about biosimilars to generate more confidence in their use across all stakeholders in the supply chain.

CfB: So, you have a terrific pipeline report on biosimilars, which is updated regularly. Can you tell us what we can look forward to in biosimilars in the insulin market in 2022?

McGowan: Yeah, sure. So, with 2 approved insulin glargine products, we'll see that market become more and more competitive once Lilly announces the launch timing of their insulin glargine that just recently received approval. We're seeing a product being developed by Sandoz that's currently in phase 3 trials. Last week, we saw an announcement that Biocon's application for its insulin aspart received a CRL [complete response letter] from the FDA but Biocon seemed to be confident that they're going to be able to provide the additional data that's required there. So, we'll see some additional markets either open up or expand in the near future.

We also have another insulin glargine from Lanett that's in the preclinical clinical trial stage. And so, we're expecting, at least based on what they've disclosed, that their clinical trials will start Q1 or Q2 in 2022. And then they're looking for FDA approval in 2023 and a potential launch in 2024.

Finally, there are about 5 rapid-acting insulin biosimilars currently in the pipeline for manufacturers including Biocon, Viatris, Sandoz, and Sanofi. And they're all in different clinical trial stages at this time, from preclinical to phase 3. So, I anticipate more of these insulin products to continue to be developed and hopefully approved and launched onto the US market in the coming years.

CfB: So, this year is shaping up to be a positioning race for adalimumab biosimilar market entry. They don't actually arrive until 2023 but what can you say about the positioning that's going on and how companies are looking to stand out in this market?

McGowan: Yeah, you're absolutely right. 2023 is going to be the year of the Humira biosimilars. And I think we're all anxiously waiting to see how this plays out. And it is going to be 1) very interesting and 2) I think a bit complicated with the number of manufacturers that are already set to launch products in 2023 [n = 7]. And then, how are they going to compete against the existing versions of Humira? So, as far as timing is concerned, Amgen will be first out of the gate with their product launching at the end of January 2023. And they're going to have about a 5-month head start over the next tranche of manufacturers that'll bring their Humira biosimilars to market. So, the next group will have Organon, [Boehringer Ingelheim], and Coherus launch their products in that middle summer timeframe, kind of end of June and early July. Then, we're going to see Viatris, Sandoz, and Pfizer launch their products between August and November in 2023. And then, we also know that Teva, in partnership with Alvotech in the development of that Humira biosimilar, is waiting for FDA approval, but launch timing is really unknown at this point.

CfB: As an aside for the Amgen now, Amgevita [adalimumab biosimilar] will have that 5-month head start. What do you think will be the lasting impact of that advantage?

McGowan: Right now, Amgen definitely is positioned to have the advantage from that timing standpoint and that head start over everybody else. Just a couple of things to take into consideration, you're absolutely right that 2023 is going to be an exciting year, but keep in mind these manufacturers are absolutely focused not only on 2023 but the several years to come after that. And so, 2023 is definitely going to be a year where the staging has taken place. Yeah, there's going to be a bit of an advantage for Amgen, and they're going to have a lot of critical decisions to make around pricing, PBM coverage, support services, patient and physician education, which is all going to have an impact on everybody else that comes after Amgen. So, I think a lot of things are going to play out, but we can't discount the fact that in the years 2024, 2025, and beyond are going to be years where these products are going to be competing. But 2023 is most certainly going to be probably the most exciting, just given the timing and the number of products that are going to come onto the market.

CfB: And 1 more question on the adalimumab pricing. What could be the effects on pricing of having so many competitors arrive on the market at the same time? Do you think that there will be a sudden drop, or do you think that given the settlements that they made with AbbVie [reference adalimumab manufacturer] that that is not going to occur?

McGowan: Yeah, that remains to be seen. I think the pricing piece is going to be interesting, just because they're going to be so many products out there and then you have this long history of AbbVie's pricing on this product. But I think a lot of the activity is going to be driven by the PBMs in which products they decide to adopt, put on their formularies, and switch patients over to. So, it's really going to be incumbent upon the manufacturers to be negotiating those deals with the with the PBMs and then which products are being adopted and which products are left off of formularies. So, at the end of the day, given that this is that pharmacy benefit space, I think the PBMs are going to play a very critical and influential role in the launch of these products.

CfB: Okay, so, etanercept has been a bit of a disappointment in terms of bringing biosimilars to market. The 2 contenders have not succeeded in breaking through the patent barriers on Enbrel [originator etanercept]. So, is there a possibility that other etanercept biosimilar makers will step forward?

McGowan: Yeah, this is certainly disappointing news for the biosimilar market, and it's been an ongoing legal battle across the last several years, especially with 2 FDA approved products out there. But the litigation rulings at this point seem to be pretty definitive. I don't foresee any manufacturers continuing to pick up the torch and continue the legal battle here, which, again, is unfortunate and it doesn't seem like we'll see an Enbrel biosimilar on the market in the US for the next several years.

CfB: In ophthalmology, ranibizumab has taken some interesting turns. Susvimo is a biobetter, some might say, and has an implant reservoir vs an injectable, which could offer great convenience to patients. Could this be a disruptor in the ranibizumab market and how could it affect biosimilar competition?

McGowan: Yeah, it’s a new market and molecule for the biosimilar markets, which is really exciting. So, it's going to be a very interesting market to watch evolve. Not only have we seen this implantable device launch onto the market, we also know that Roche/Genentech is developing their faricimab molecule, which will have retina-ophthalmology indications. So, we'll have to see how successful they will be at launching that product, which will have patents and exclusivities if and when it's approved, and then how successful they'll be in converting patients over to that product. We also have another organization and company with Outlook Therapeutics actually developing a bevacizumab product specifically for the retina-ophthalmology indications. So, that's going to be a little bit of a nuanced wrinkle and addition into an already complex and competitive market.

But on the biosimilar front, there's currently only 1 approved product from Biogen with Byooviz. And we're anticipating at least 3 other biosimilars referencing Lucentis to come onto the market in the next 2 to 3 years. So, Biogen is most certainly going to be the first product on the market in this space and what's been announced is a mid-2022 launch for that product. But it's going to be very interesting to see how the practitioners and the practices get educated on biosimilars, since they most likely have not utilized a biosimilar in the past, and how to build those into their care plans and adopt these products. Given the complexity and how heavily competitive this market is, given the innovator company's position, a new branded product coming to market, and then several biosimilars, it's going to be another very interesting market to watch evolve.

CfB: Yeah, affordability is a tremendous issue in ophthalmology. So, what else might move the needle in the biosimilar pipeline events in 2022?

McGowan: Looking ahead to calendar year 2022, I think there are a few opportunities and challenges to look for. So, going back to Semglee's launch and the availability of 2 versions, a branded and unbranded, we'll be watching closely as to how these products compete in the commercial market vs the Medicare/Medicaid or Part D plans. So, which version of the product is going to get adopted and how quickly can it grow and into what levels? And then what learnings can manufacturers glean from the strategy that Viatris has taken, and can they take those learnings and apply them to other biosimilar markets, and I think Humira is 1 specifically that jumps right to the front of my mind. So, can this type of strategy be replicated in other markets? In staying on the topic of Humira, the approval and the launch of Semglee will most certainly act as kind of a dress rehearsal for bigger biosimilar market entrance expected in the Part D space in 2023. So, having an interchangeable product and having a Part D product, a pharmacy benefit product, is most certainly going to provide a lot of learnings and education around how the pharmacists' handle these products, how the pharmacy benefit managers handle these products, how they're positioned on the formularies, and how that interchangeable designation is treated at the pharmacy counter.

And then there's some excitement in the medical benefits of the Part B space with the forthcoming launch of the first biosimilar in the retina-ophthalmology space in Byooviz, which references Lucentis and we've talked about just a minute ago. Again, that launch is expected to happen mid-year in 2022. 2022 is also going to be the year where everyone is preparing for the watershed moment of the 7 plus biosimilars referencing Humira coming onto the market starting in 2023. And with the 7 plus Humira biosimilars entering the retail and specialty pharmacy space, a whole new customer group and market will be introduced to biosimilars. So, again, kind of going back to my point earlier around the education piece and how this continues to be a critical element to improve the adoption of biosimilars, the aperture expands exponentially as these retail pharmacy and specialty pharmacy products come onto the market.

And then just some considerations for the biosimilar market moving forward. We'll continue to watch how manufacturers of innovative products respond to biosimilars. A great example, Janssen towards the end of 2021 launched an unbranded version of Remicade [originator infliximab] similar to how Semglee was launched both branded and unbranded. Now, we've got an innovator product in the Part B space with a branded and unbranded [version]. We'll most certainly make note of whether or not this strategy is successful and then whether or not other innovator companies adopt a similar strategy. We're also expecting to see a new set of manufacturers launch biosimilar products into existing markets, as well as new biosimilar markets like Biogen with their Lucentis biosimilar. Finally, existing biosimilar markets will become more competitive with new entrants. All of this is really great in my opinion because these manufacturers continue to see an opportunity for biosimilars, and patients will benefit from increased competition that helps improve access and affordability.

CfB: Terrific, Sean, thanks. Finally, the Build Back Better Act has been through a lot of drafts, and we don't know whether it's going to see the light of day. What are your thoughts on how this might affect biosimilars in the final version, if there is one?

McGowan: Yeah, that's a great question and I know a lot of focus on the Build Back Better Act was paid in the November timeframe before the legislators shut it down for the end of the year. We're going to be following this very closely to see what policies actually make it into the bill, in whatever way shape or form that happens. I think we all want to see policies that continue to support a market that allows for biosimilar competition, encourages manufacturers to invest in the space, and helps to bring down drug prices and the overall cost of care. Despite all the challenges and hurdles the biosimilar market has had to overcome across the last several years, biosimilars have most certainly delivered on their promise to expand access, drive down costs, and deliver on savings.

CfB: Thanks very much, Sean. It's great talking with you again about biosimilars at The Center for Biosimilars.

Sean McGowan, senior director of Biosimilars for AmerisourceBergen, forecasts potential biosimilar approvals and launches in 2022 as well as offers insights into how emerging biosimilars will impact the market and pricing in the coming years during an interview.

AmerisourceBergen Rep Previews the Year Ahead for Biosimilars: What’s Coming Down the Pipeline in 2022?

Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

Entering 2020, we have the opportunity to take a moment, look back, and reflect on the lessons learned of the previous decade with regard to biosimilars. The road to a successful biosimilars market has been anything but straightforward. With complications including a slow rate of approval, extended delays in product launches due to patent litigation, or the small and incremental degree of economic impact, it’s easy to become frustrated and question whether or not biosimilars represent an economically prudent investment in the new decade. 

While I would not argue with anyone that we should expect more from the biosimilars opportunity, simply throwing the baby out with the bathwater at this point would be a monumental mistake that fails to see the growing opportunity the space provides us. Essentially, these hurdles are not as insurmountable as they appear and can be managed if we focus our approach at the appropriate obstacles and recognize the benefits to continued biosimilar development beyond simply the primary goal of lowering the price of biologic drugs. 

The Elephant in the Room: What is a Fair Price?

While the question of pricing is critically important, we must also acknowledge the other structural and economic realities of drug prices. One prominently articulated alternative to biosimilars is the implementation of pricing regulation for biologics after they reach the end of their exclusivity period. This approach would attempt to establish a “fair price” at which an originator biologic will be sold that is intended to include all of the expenses associated with biologic development and the ongoing supply of that product. However, there are several issues with this concept that should be addressed:

Given the current political landscape, it appears rather remote that agreement on a price setting process for biologics or any other pharmaceuticals could be established within the near future.

The creation of this “fair price” would require a degree of transparency from the pharmaceutical industry far beyond anything that presently exists. Currently, there are little if any details concerning the true cost of drug development, high quality manufacturing, and consistent supply. 

The most challenging aspect of this endeavor would be establishing an agreed upon definition of a “fair price.” Given the number of stakeholders involved in and impacted by the pricing of pharmaceuticals, it appears highly unlikely that these participants would agree to a threshold for profit generation.

Realigning our Understanding of Biologics, Generics, and the Concept of Cost

Much of the recent frustration with biosimilars stems from our previous experience with generics. Over the last 35 years, generics have demonstrated that competition can drive dramatic savings with the value being recognized almost immediately. The simplicity of the molecules and the well-established mechanism of declaring products interchangeable, creates a clear pathway for competition. However, the US healthcare market is now closing in on the second decade of a drug shortage crisis that has primarily centered on the persistent and extended interruptions in the supply of hundreds of generic medications.

As a result, we must re-examine our traditional perspective that it is always easy to create generic drugs and always hard to create biosimilars. We have learned that all pharmaceuticals require a great degree of due diligence and commitment to quality. Perhaps the modest barriers to generic entry have been too low to ensure a long-term and consistent availability of high-quality small molecule drugs. Rather than stopping biosimilar development, we should use this ongoing experience to improve our understanding of safe, effective, and sustainable manufacturing for all medications.

A Holistic Approach to Enter the New Year

We are still early in the biosimilars experience and are continuing to make strides in addressing many of the challenges that have slowed and diluted the extent of financial impact. Even with these challenges, the future of biosimilars looks exceedingly bright. According to a report by Global Market Insights, by 2025 the global biosimilars industry is poised to surpass a valuation of $69 billion. However, that will be merely a dream if we are unable to address those hurdles. So what are our next steps? 

Physicians and other clinicians need to understand the concepts of risk management to avoid unnecessary apprehension. If clinicians become more comfortable with the analytical characterization methods to monitor changes in biologics, we move closer to a day when redundant clinical studies are no longer required.

The manufacturing of biosimilars must be monitored closely to avoid any negative impact on product quality. An increased degree of scrutiny of small molecule drugs, including generics, is also important.

We must continue to leverage our advocacy capabilities to remove additional barriers such as the use of excessive patenting to delay the introduction of competition.

Long-term resolution to our challenge of lowering the cost of medications must at some point address the way in which providers are reimbursed. As long as physicians and other providers are reimbursed in a way that higher acquisition costs lead to larger reimbursement opportunities, acceptance of competing products, biosimilars or other, will continue to be limited.

Hurdles to a vibrant biosimilar market are not as insurmountable as they appear.

Understanding the Risks, Opportunities, and Prospects of Biosimilars in 2020 and Beyond

Steven Lucio, PharmD, BCPS

Mauricio Rubio is a pharmacist with advanced studies in administration, and he is currently a master of business administration candidate. He has 13 years of experience in sales, marketing, and business development in Latin America for pharmaceutical and consultancy companies. He has participated as a speaker in the Jack Leckerman Biosimilars Forum in 2018 and 2019.

Mauricio Rubio

Carlos Sattler, MD, is the head of clinical development and medical affairs at Sandoz, Inc. In this capacity, Sattler leads efforts in the United States to develop and implement Sandoz’s medical and scientific strategy, medical education and communication initiatives, and data-generation activities in support of biosimilars and other Sandoz products. Sattler specialized in pediatric medicine and is subspecialty trained in pediatric infectious diseases.

Carlos Sattler, MD

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/

Authors