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WHEN CHOICE ARRIVES: Competition & Consequences

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BIOSIMILAR APPROVALS

Sarfaraz K. Niazi, PhD, is an adjunct professor of biopharmaceutical sciences at the University of Illinois and the University of Houston, and founder of biosimilars companies Karyo Biologics and Adello Biologics. He also founded the biosimilar advisory company PharmSci.

Articles

The Biologics Price Competition and Innovation Act (BPCIA) of 2010 initially posed significant barriers to biosimilar development, but regulatory reforms over the years have drastically reduced costs and approval times, with further advancements expected by 2025 that will foster competition and drive down prices.

BioRationality—The Evolution of the BPCIA and the Bright Future of Biosimilars in the US

On this episode of Not So Different, we discuss the FDA's approval of a new biosimilar for treating retinal conditions, which took place in September 2024 alongside other major industry developments, including ongoing legal disputes and broader trends in market dynamics and regulatory challenges.


Biosimilars Policy Roundup for September 2024—Podcast Edition

A retrospective study of a mandatory nonmedical switch in Canada found no significant differences in rates of treatment persistence, loss of response, or adverse events in patients with inflammatory bowel disease (IBD) on maintenance therapy 1 year post-switch.  

Treatment Persistence, Safety After Switching to Infliximab Biosimilars in Canadians With IBD

Cameron Santoro is an associate editor for The Center for Biosimilars

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Here are the top 5 biosimilar articles for the week of September 30, 2024.

The Top 5 Biosimilar Articles for the Week of September 30

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Mark Campbell, PharmD, is the chief pharmacy officer at RxBenefits.

For biosimilars to overcome these entrenched market dynamics, they must not only compete on price but actively work to build a network of support among providers and patients.

A Promise Unfulfilled: The State of Biosimilars

The FDA approved a new strength of a trastuzumab biosimilar; UnitedHealth will remove reference adalimumab from some preferred drug lists in favor of biosimilars and Evernorth will offer an interchangeable ustekinumab biosimilar at no cost to patients; Samsung Bioepis received a positive regulatory opinion for its aflibercept biosimilar.

FDA Approves Higher Strength of Trastuzumab Biosimilar

 the 420 mg strength of Hercessi (trastuzumab-strf), a biosimilar to Herceptin (trastuzumab), for the treatment of HER2-positive breast and gastric cancers. This follows an earlier approval of the 150 mg strength in April 2024, positioning Accord BioPharma, the US specialty division of Intas Pharmaceuticals, for a US commercial launch of its first biosimilar in early 2025.

Hercessi targets HER2-overexpressing cancers by inactivating the HER2 receptor, slowing cancer cell replication. The FDA’s decision was based on extensive studies showing the new higher dose of Hercessi’s efficacy, safety, and quality were equivalent to Herceptin. This approval marked a significant milestone for Accord’s entry into the US market, with plans to launch additional biosimilars, including pegfilgrastim and ustekinumab, in the near future. Hercessi was developed by Accord’s partner, Shanghai Henlius Biotech, which granted Accord exclusive rights to bring the biosimilar to the US and Canadian markets.

Humira and Stelara Face Coverage Challenges Amid Biosimilar Competition

UnitedHealth Group announced it will remove AbbVie’s Humira (reference adalimumab) from some of its preferred drug lists starting January 1, 2025, in favor of less expensive biosimilars for commercial health plans managed by its pharmacy benefits unit, Optum Rx. According to a report from 

, this makes Optum the last of the 3 largest US pharmacy benefit managers (PBMs) to exclude Humira, following similar moves by Cigna’s Evernorth and CVS’ Caremark. Together, these PBMs control about 80% of the US prescription drug market.

Despite the launch of 10 adalimumab biosimilars since January 2023, AbbVie has maintained a dominant market position, although it anticipates a reduced share in 2025. The US market share for adalimumab biosimilars has grown to nearly 20% this year. UnitedHealth will continue to provide coverage for Humira until the FDA designates certain biosimilars as interchangeable, expected in 2025.

 that starting next year it will offer an interchangeable ustekinumab biosimilar to Johnson & Johnson’s Stelara (reference ustekinumab) at $0 out-of-pocket cost for eligible patients through its specialty pharmacy, Accredo. Produced by affiliate distributor Quallent Pharmaceuticals, this biosimilar will offer over 80% savings compared with Stelara, helping patients save around $4,000 annually through Quallent’s co-pay assistance program.

Evernorth’s initiative aims to lower costs for the more than 30,000 Accredo patients currently on Stelara, as well as for health plan sponsors. Humira biosimilars, also available at $0 out-of-pocket cost through Accredo, could save patients around $3,500 annually.

These changes come amid increased regulatory scrutiny of PBMs over their influence on prescription drug pricing. While PBMs claim to reduce costs through competition, the Federal Trade Commission has criticized them for overcharging patients, citing their vertical integration and market power. PBM executives, however, argue that pharmaceutical companies' complex patent strategies are to blame for high drug prices.

EMA’s CHMP Gives Positive Opinion for Aflibercept Candidate

Samsung Bioepis announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive scientific opinion on Opuviz (SB15), a biosimilar candidate referencing Eylea (aflibercept). As reported by 

, the positive opinion follows a thorough review of the marketing authorization application submitted earlier this year, marking a critical milestone in the approval process by the European Commission. A formal decision on marketing authorization is typically expected within 2 to 3 months of a positive opinion.

Opuviz is designed to treat ophthalmic diseases such as wet age-related macular degeneration and is a biosimilar to Eylea, developed by Regeneron. Eylea works by inhibiting new blood vessel formation through binding to vascular endothelial growth factor. The global market for Eylea reached approximately 12 trillion won ($8.9 billion) in 2023. Biogen, Samsung Bioepis’ partner for the US and European markets, will handle the marketing and distribution of Opuviz in Europe once final approval is granted.

“We are delighted to have received a positive opinion for Opuviz, our second ophthalmology biosimilar, following Byooviz,” said Samsung Bioepis Regulatory Affairs Vice President Jung Byung-in. “We will continue to expand our product portfolio to offer more treatment options for patients globally.”

1. Accord BioPharma, Inc. announces U.S. Food & Drug Administration approval of 420mg strength of Hercessi™ (trastuzumab-strf), a biosimilar to Herceptin® (trastuzumab), for the treatment of several forms of HER2-overexpressing cancer. Accord Biopharma. Press release; September 18, 2024. Accessed September 24, 2024. 

https://www.biospace.com/press-releases/accord-biopharma-inc-announces-u-s-food-drug-administration-approval-of-420mg-strength-of-hercessi-trastuzumab-strf-a-biosimilar-to-herceptin-trastuzumab-for-the-treatment-of-several-forms-of-her2-overexpressing-cancer

2. Wingrove P. UnitedHealth to remove AbbVie's Humira from some US drug reimbursement lists next year. Reuters. September 10, 2024. Accessed September 24, 2024. 

https://www.reuters.com/business/healthcare-pharmaceuticals/unitedhealth-remove-abbvies-humira-some-us-drug-reimbursement-lists-next-year-2024-09-10/

3. Manalac T. Cigna continues biosimilar push, targets J&J’s Stelara with no out-of-pocket cost. BioSpace. September 6, 2024. Accessed September 24, 2024. 

https://www.biospace.com/business/cigna-continues-biosimilar-push-targets-j-js-stelara-with-no-out-of-pocket-cost

4. H-S Lee. EMA issues positive view on Samsung Bioepis’ Eylea biosimilar. Korea Biomedical Review. September 23, 2024. Accessed September 24, 2024. 

https://www.koreabiomed.com/news/articleView.html?idxno=25196

Clinical

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Eye on Pharma: High-Strength Trastuzumab Biosimilar; Originator Coverage Removals; CHMP Aflibercept Opinion

 written by Vibeke Strand, MD, clinical professor in division of immunology/rheumatology at Stanford University School of Medicine, gave an overview of 

The trial found similar efficacy and safety of the adalimumab biosimilar Cyltezo (adalimumab-adbm; Boehringer Ingelheim) and the reference product (Humira) in patients with moderate to severe rheumatoid arthritis (RA). “Similar substantial benefits across a range of patient-reported outcomes” were reported in VOLTAIRE-RA participants randomized to the biosimilar and originator, Strand wrote.

Adalimumab is a monoclonal antibody targeting tumor necrosis factor-α that has been approved in the US since 2002 and Europe since 2003, and adalimumab-adbm was the first biosimilar adalimumab product approved as 

The summary explained that participants who received the biosimilar had similar symptom reduction and side effects as those who received the reference product and then switched to the biosimilar. Participants were randomized to the biosimilar or reference product for the first 24 weeks, at which point half of the patients on the reference product were randomized to switch to the biosimilar. PROs were recorded at 12 and 24 weeks after the start of treatment to assess whether there were differences in the effects of biosimilar and reference product treatment on health-related quality of life.

Participants in the study completed a 36-item questionnaire (SF-36) to assess patient-reported health status across eight domains: physical functioning, physical role limitations, bodily pain, general health perceptions, energy/vitality, social functioning, emotional role limitations, and mental health. These outcomes are evaluated individually and grouped into the physical component summary score and mental component summary score. Patients also completed surveys assessing their perception of their disease activity and health-related quality of life.

At 12 and 24 weeks, the 2 treatment groups showed similar improvements in both physical and mental component summary scores. Mental component scores improved by 70% in the reference product group and 68% in the biosimilar group, physical component score by 59% and 56%, levels of improvement considered clinically important. There were no significant differences in physical component summary scores between groups at baseline, week 12, or week 24. Mental component summary scores were somewhat higher in the reference product group at baseline, but improvements at weeks 12 and 24 were similar between groups.

Improvements across all domains showed no significant differences between groups. Regarding individual domains, the author explained that more than two-thirds of participants reported clinically meaningful improvements in domains such as physical functioning, bodily pain, and vitality, and more than half reported improvements in others such as general health, emotional role limitations, and social functioning.

According to the summary, the VOLTAIRE-RA trial found people with rheumatoid arthritis receiving either the biosimilar adalimumab-adbm or the reference product experienced similar improvements in symptoms and similar levels of side effects, and these effects “translated into highly similar clinically meaningful improvements in experience and perception.” The author added that “a high proportion” of participants in the trial reported greater improvements compared to a reference US population similar in age and sex, and this finding “represents attainment of a treatment goal that was difficult to achieve in early trials of non-biologic treatments for rheumatoid arthritis.”

Strand V. Summary of research: effects of adalimumab-adbm versus adalimumab reference product on patient-reported outcomes in rheumatoid arthritis: results from VOLTAIRE-RA. 

. Published online August 9, 2024. doi: 10.1007/s40744-024-00691-0

A summary of research written by Vibeke Strand, MD, clinical professor in division of immunology/rheumatology at Stanford University School of Medicine, gave an overview of patient-reported outcomes (PROs) in the VOLTAIRE-RA trial.

Patient-Reported Outcomes Similar Between Adalimumab-adbm, Reference Product in VOLTAIRE-RA Study

 assessing patient satisfaction with adalimumab for inflammatory bowel disease (IBD) reported overall “a high level of satisfaction with adalimumab treatment.” The survey responses showed higher levels of overall patient satisfaction for Hulio, Humira, and Amgevita, and higher levels of satisfaction with the injection device for Yuflyma, Hulio, and Humira, compared to other adalimumab products.

Adalimumab, a monoclonal antibody targeting tumor necrosis factor-α, is used to treat moderate to severe Crohn disease (CD) and ulcerative colitis (UC), chronic inflammatory diseases of the digestive tract collectively called IBD. After patent expiration of the reference product (Humira), several biosimilars became available in Europe. However there are differences in dosage, formulation, and delivery devices across biosimilars. The investigators pointed out that these factors and their impact on adverse events and quality of life can influence a patient’s satisfaction with treatment, which in turn influences treatment compliance, persistence, and adherence. For example, the presence of citrate and larger injection volume in adalimumab products have previously been shown to be associated with pain at the injection site.

The nationwide study in France in centers affiliated with the Groupe d’Etude Therapeutique des Affections Inflammatoires du tube Digestif (GETAID) investigated the satisfaction of patients with IBD with adalimumab biosimilars and the reference product. The study surveyed 941 patients with IBD being treated with adalimumab, 797 (85%) with CD and 141 (15%) with UC, across 45 centers affiliated with the GETAID over 2 2-week periods in 2022. Patients had a median time since diagnosis of 11 years, and most patients were in clinical remission at inclusion. Participants completed a satisfaction questionnaire consisting of 4 items each rated by a 10-point scale: overall satisfaction with adalimumab; satisfaction with the subcutaneous injection form; satisfaction with the injection kit; and satisfaction with support services. In addition, the survey asked about patient characteristics, treatment characteristics, injection site reactions, and previous treatment with different adalimumab products.

Humira (46%), Amgevita (19%), and Hulio (11%) were the most commonly used adalimumab products, followed by Idacio (7%), Hyrimoz (6%), Yuflyma (6%), Imraldi (4%), Amsparity (1%), and Hukyndra (0.1%). The mean overall satisfaction score for adalimumab treatment was 8.5/10 (SD, 1.8), 8.6 (SD,, 1.5) for Humira, 8.6 (SD, 1.8) for Hulio, 8.5 (SD, 1.4) for Amgevita, 8.2 (SD, 1.8) for Hyrimoz, 8.2 (SD, 1.5) for Idacio, 8.2 (SD, 1.7) for Imraldi, 7.8 (SD, 2.1) for Yuflyma, and 6.5 (SD, 2.3) for Amsparity. Overall satisfaction was significantly higher in patients treated with Humira compared to Amsparity or Yuflyma, in patients treated with Hulio compared to Amsparity, and in patients treated with Amgevita compared to Amsparity.

Most patients (83%) used pen devices for subcutaneous injection and performed injections themselves. The mean satisfaction score for an injection pen device was 8.7 (SD, 1.6) and 8.7 (SD, 1.5) for a syringe. Mean satisfaction with the subcutaneous injection form was 9.0 (SD, 1.4) in patients receiving Yuflyma, 8.9 (SD, 1.3) for Humira, 8.9 (SD, 1.7) for Hulio, 8.7 (SD, 1.6) for Amgevita, 8.5 (SD, 1.6) for Hyrimoz, 8.1 (SD, 2.2) for Idacio, 7.8 (SD, 2.2) for Imraldi and 7.2 (SD, 2.5) for Amsparity. Patients receiving Yuflyma, Humira and Hulio rated their satisfaction with the subcutaneous injection form significantly higher than those receiving other adalimumab products.

Satisfaction with the injection kit was rated 8.8 (SD, 1.3) by patients treated with Amsparity, 8.1 (SD, 2.4) for Imraldi, 8.1 (SD, 1.9) for Yuflyma, 7.7 (SD, 2.0) for Amgevita, 7.7 (SD, 2.4) for Idacio, 7.6 (SD, 2.3) for Humira, 7.6 (SD, 2.6) for Hyrimoz, and 7.3 (SD, 2.5) for Hulio. About one-third of patients (32%) reported they did not receive an injection kit at the start of treatment.

Most patients (70%) reported they did not use support services, such as assistance calls, websites, or videos, and 17% reported that no support services had been offered.Mean patient satisfaction with support services was 6.0 (SD, 3.1) in patients receiving Amgevita, 5.4 (SD, 2.7) for Yuflyma, 5.2 (SD, 2.7) for Imraldi, 5.1 (SD, 3.4) for Idacio, 5.0 (SD, 3.3) for Hulio, 4.7 (SD, 3.5) for Humira, 4.5 (SD, 3.7) for Hyrimoz, and 3.8 (SD, 4.7) for Amsparity.

Of the 941 total patients, 299 (32%) reported they had experienced injection site reactions, including 50% of those treated with Amsparity or Imradi, 48% receiving Idacio, 40% receiving Yuflyma, 34% receiving Humira, 28% receiving Hyrimoz, 23% receiving Amgevita, and 17% receiving Hulio. A total of 223 (24%) participants reported previous treatment with a different adalimumab product, of which 32 (14%) discontinued treatment with the previous product due to side effects, and the rest switched from the reference product to a biosimilar. Fourteen of the 32 patients who discontinued the previous adalimumab product due to side effects reported persistent injection site reactions after switching.

The authors concluded that patients with IBD in their study had a high level of satisfaction with adalimumab treatment, “with some differences in terms of overall satisfaction and satisfaction with the injection device.” They said their findings suggest Hulio, Humira, and Amgevita benefit overall patient satisfaction, and Yuflyma, Hulio, and Humira benefit patient satisfaction with the injection device. Currently, they said, the choice between adalimumab products is usually based on non-medical considerations, such as costs or additional services for patients. Since patient satisfaction is associated with better treatment adherence, the authors wrote, “we need to look beyond efficacy and safety by investigating patient satisfaction to be able to make the right choice.”

Caron B, Seksik P, Buisson A, et al. Patient preferences for adalimumab in inflammatory bowel disease: a nationwide study from the GETAID. 

. 2024;17:17562848241265776. doi:10.1177/17562848241265776

An observational study assessing patient satisfaction with adalimumab for inflammatory bowel disease (IBD) reported a high level of satisfaction with all adalimumab product, including biosimilars.

French Study Finds High Patient Satisfaction With Adalimumab Biosimilar Treatment for IBD

The arrival of biosimilars brought a slew of associations, expert opinions, political interventions, marketing discussions, and many more online discussions. Experts were born, scientists came up with complex ideas, statisticians published papers, the US Congress went into action, and the pharmacy benefits managers (PBMs) bumped into receiving the most significant financial break.

As someone who’s been engaged in this space since before the term “biosimilar” was coined, I want to share my opinion about why there is so much irrationality in the introduction of biosimilars, albeit at the risk of challenging the deniers.

Biosimilars could have been just another generic drug with no hoopla. Still, biologic drugs were excluded from generic treatment because of the structural variability even for therapeutic proteins, even though that is not as large as a bacterial vaccine. The Hatch-Waxman Act of 1984, also known as the Drug Price Competition and Patent Term Restoration Act, made it easier and less expensive for manufacturers to enter the generic drug market. The Act established an abbreviated new drug application (ANDA) process that allowed manufacturers to apply for FDA approval before the patent on an existing drug expired.

The first ANDA approved under the Act was for generic disopyramide to treat cardiac arrhythmias. Many large pharmaceutical companies initially opposed the Act, arguing that it would disincentivize innovation and hurt patients. However, recognizing the profitability of generic drugs, many big pharma companies eventually entered the generic market, often through subsidiaries or partnerships.

Despite their involvement, these companies tend to exit once intense competition drives prices down to less profitable levels. This cycle has led to the establishment of large, dedicated generic manufacturers, like Teva Pharmaceuticals and Mylan (now Viatris), dominating the space.

Generics are priced, on average, 80% to 85% lower than their brand-name counterparts. The initial steep decline in price occurs when the first few generics enter the market, and a more significant change comes when more generics become available. This is not happening with biosimilars; there are only 16 molecules available as biosimilars. So, there is nothing different in the history of biosimilars than the history of generic drugs. Many big pharma companies have jumped into the race and maintained their interest because the price has yet to drop 80% more universally. I predict that this will happen as competition rises, which is currently being kept low due to the high cost of development for biosimilars. In my opinion, a rational mind would conclude that it is all in the regulatory guidelines to modulate. Instead, all promoters of biosimilars talk about how much biosimilars would have saved or will save as if this were news. None of them have given attention to the cause of the lack of competition because it required a scientific investigation and contribution that is not their area of expertise.

The FDA, European Medicines Agency (EMA), and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA), among other significant agencies, have dramatically changed the approval guidelines once the fear of disaster created by big pharma is reduced, saying that only they know how to make these drugs. If the primary, secondary, and tertiary structures of the drugs are the same, which is quickly confirmed, the risks are no different than any other drug administered parenterally. However, the regulatory agencies are not in the business of being rational at the risk of being blamed; a good example is that the FDA and EMA have yet to declare the futility of clinical efficacy testing, which adds about 75% of the development cost. None of the promoters of biosimilars have worked on promoting this thought to the FDA; all I see is a redundant declaration that biosimilars are saving money.

While the MHRA has been more rational, I anticipate both EMA and FDA will agree with MHRA and remove efficacy testing; this direction is evident from the recent FDA move to remove the redundant switching and alternative testing of approved biosimilars to receive an interchangeable status. All agencies have approved the biosimilars with pharmacodynamic markers, but this is not necessary since any biological property is proportional to the plasma concentration profile that is easily compared—no different than the traditional bioequivalence studies. Such studies are not required for generic drugs administered parenterally. Still, in the case of biosimilars, it is necessary to ensure that the subtle structural differences do not affect disposition kinetics.

So, what should be the rational path to making biological drugs more affordable is to reduce biosimilars' cost of goods (COGs). The first element is the media that is commercially supplied at a high premium; we should be able to switch to in-house media using the lowest cost components. Second, switch to continuous manufacturing as the FDA has recently suggested. And third, let the United States Pharmacopoeia create release specification, thus eliminating analytical assessment studies—all of it will reduce the COGs significantly so that biosimilars will likely become available to patients for a cost no different than what they pay today for generic drugs, but only if we better align PBM practices with that goal.

The article by Sarfaraz K. Niazi, PhD, critiques the irrationality surrounding biosimilars, suggesting that regulatory changes and cost reductions in manufacturing could make biosimilars as affordable as generic drugs.

BioRationality—The Missing Rationality in Biosimilar Discussions and the Path Forward

Sophia Humphreys, PharmD, MHA, BCBBS, director of system formulary management at Sutter Health, discusses the challenges of expanding biosimilars into new therapeutic areas and highlights the role of education, competitive pricing, and integrated delivery networks (IDNs) in improving adoption and market growth.

’s Institute for Value-Based Medicine (IVBM) event in Seattle, Washington, cohosted with Providence. During the event, she presented on pharmacoeconomic impacts of biosimilar market expansion and participated in a panel discussion. The IVBM event highlighted integrative approaches in neuroscience population health, with additional presentations on the Alzheimer disease landscape, nonopioid pain management, and the impact of biosimilar market expansion.

How do new therapeutic classes and indications for biosimilars influence market expansion?

 I think this goes beyond just patient education. For example, when we started with biosimilars for cancer—curative and supportive agents—they were quickly adopted. But once we moved into immunology, endocrinology, and ophthalmology, we observed more hesitation. One reason is that many of these are maintenance therapies. We’re not talking about starting a new treatment plan but convincing patients who may have already failed several therapies before reaching the [reference] biologic to switch to a biosimilar.

So, first, we needed to educate both patients and providers that biosimilars are highly similar to the reference product. There's no evidence of reduced efficacy, increased immunogenicity, or new safety concerns. Over the past 10 years, we’ve used biosimilars successfully. We also needed to address health care system leaders that expanding biosimilar use across therapeutic classes can increase access to lifesaving, life-altering medications for more patients.

What are the key factors driving competition among adalimumab biosimilars in the market?

 Adalimumab has been a favorite molecule since July 2023, and several factors play a role. It’s quite similar to what we saw with infliximab in autoimmune diseases. Many of these patients are on maintenance treatments. With adalimumab, a key issue is matching the existing product patients are used to. For example, if my patient is using a citrate-free product, you probably don’t want to switch them to a product that isn’t citrate-free, as that could cause more injection-site discomfort. Another consideration is concentration—many patients prefer a higher-concentration formulation.

Interchangeability is also a factor. In states that allow pharmacy-level switching, when a physician prescribes the reference product, a pharmacist can switch it to an interchangeable biosimilar without new authorization. Each state has its own regulations, including the need to inform patients and physicians about the switch. Lastly, we have to ensure the biosimilar is covered by the patient's payer and offers comparable patient support, such as co-pay assistance. For 340B sites, the impact on 340B accumulation must also be considered. These are comprehensive considerations.

What pricing strategies have been employed in the adalimumab biosimilar market, and how effective have they been?

 That’s a $20 billion question. By the end of 2023, we saw 2 main strategies: high WAC [wholesale acquisition cost] with high rebates and low WAC. Almost all biosimilar companies have adopted 1 [or both] of these strategies.

Unfortunately, by the end of 2023, according to IQVIA’s biosimilar report, we hadn’t seen a high adoption rate—less than 5%. However, when infliximab was introduced, its first-year uptake didn’t exceed 5% either. So, while it’s early, we’re already seeing a benefit as [reference] products reduce prices due to competitive pressure. In my view, biosimilars delivered a win to both the health care industry and patients in 2023.

How does the adalimumab biosimilar market serve as a case study for the broader biosimilar industry?

 Time will tell. Adalimumab biosimilars are working hard to promote their products, engage with payers, and connect with patient groups. I hope that in 2 or 3 years, we’ll be able to differentiate which product strategies were more effective—whether interchangeability made a difference, whether high-concentration vs low-concentration mattered, and if syringe size or citrate-free options enhanced adoption. For now, we’re still in the learning phase.

What lessons can be learned from markets with high biosimilar adoption rates to improve uptake in slower markets?

 That’s a great question. First, we need to differentiate between medical benefit and pharmacy benefit. Many of the most successful biosimilars are in the medical benefit space, especially in the "buy and bill" space. IDNs that work closely with GPOs [group purchasing organizations], 340B branches, and formulary management teams perform regular reviews of coverage, patient mix, and ASP vs acquisition cost. This helps them decide which biosimilars to prioritize. Additionally, some IDNs have built biosimilar tools into their EHR [electronic health record] systems to streamline physician workflows. Physicians are extremely busy and can’t be expected to remember which product to use each quarter, so it’s important to build support into the system. Some IDNs have also incorporated prior authorization processes for both the reference product and biosimilars, further streamlining care. Finally, it’s crucial to conduct regular performance reviews and share success metrics with leadership. This continuous improvement process elevates the entire system.

How have early adopters of biosimilars influenced the overall acceptance of these products?

 Early on, systems like Kaiser Permanente, Providence, Yale New Haven, and University Hospitals published data on the success of their biosimilar programs. This real-world evidence from large IDNs across different therapeutic classes has shown several common success factors, such as starting early and conducting comprehensive pharmacoeconomic analysis. Smaller and rural hospitals, which may lack the resources of larger systems, can learn from these pioneers. Early adopters carry the initial resistance, but they also pave the way for the rest of the market to follow.

What strategies should IDNs employ to effectively incorporate biosimilars into their formularies?

 IDNs should stay ahead of the game by closely monitoring FDA approvals and evaluating biosimilars as soon as they are approved. This supports contracting teams when negotiating with GPOs or biosimilar manufacturers, allowing them to promise market share in exchange for beneficial contracts.

Collaboration with payers is also crucial. And ArchMed has published its data showing that its biosimilar-first policy significantly reduced PMPM [per-member per-month] costs. These strategies help harvest the cost-saving potential of biosimilars for both health care systems and patients.

Sophia Humphreys, PharmD, MHA, BCBBS, director of system formulary management at Sutter Health, discusses the challenges of expanding biosimilars into new therapeutic areas and highlights the role of education, competitive pricing, and integrated delivery networks in improving adoption and market growth.

Expanding Biosimilar Adoption: Insights and Strategies With Dr Sophia Humphreys

Gastroenterologists generally are accepting of biosimilars for initiating therapy in patients who are biologics-naïve. However, they remain skeptical of switching patients to biosimilars if their disease is successfully managed with an originator biologic.This practice is called nonmedical switching, and it may be done to get patients on a less expensive form of the same therapy.

 of nonmedical-switching studies of patients with inflammatory bowel disease (IBD) has detailed the knowledge gaps and study limitations responsible for this hesitation by gastroenterologists.

The majority of studies thus far have suggested nonmedical switching from infliximab to its biosimilar CT-P13 (Inflectra; Remsima) is safe. Previous reviews have 

The systematic review identified 44 studies on switching patients from infliximab (Remicade), the first biologic marketed for use in IBD, to the biosimilar CT-P13; however, only 3 were randomized controlled trials (RCTs), only 1 of which has been published. Approximately half of the studies reviewed by the authors, most of which were observational and not intended to change treatment patterns, were not yet published.

The authors of the current review concede that “safety and efficacy of biosimilar use in infliximab-naïve patients is generally accepted,” but they advise caution on nonmedical switching because of study limitations that include the small number of RCTs compared with observational studies, lack of controls in observational studies, lack of long-term data, and a reliance on studies published at conferences for which key study design details are missing.

 by Frank I. Scott of the Crohn’s and Colitis Center at the University of Colorado Anschutz Medical Campus agrees that more research is needed before nonmedical switching can be widely adopted.

The review authors found shortcomings with the single published RCT, the 

, which studied a switch from originator infliximab to the biosimilar in 6 inflammatory diseases, including IBD. The study included the use of a composite measure of disease worsening across the same 6 heterogeneous inflammatory diseases, with different dosing regimens and concomitant therapies.

The authors also criticized the inclusion criteria for the trial as having “ill-defined disease-specific criteria,” which they said “introduces the potential for bias and limits the inferences that can be extrapolated to IBD.” Furthermore, they criticized the noninferiority margin, which they say could have demonstrated noninferiority even if up to 50% of the patients switched to CT-P13 experienced disease worsening, based on enrollment numbers.

Although the NOR-SWITCH trial demonstrated noninferiority and included patients with IBD, the data presented on ulcerative colitis and Crohn disease (CD) “did not allay” the concerns of gastroenterologists regarding switching their patients on infliximab to a biosimilar, according to the editorial. The review authors noted “the trend toward increased disease worsening in CD patients has caused some concern in the gastrointestinal community and a desire for more robust data in IBD patients.”

In an IBD subgroup open-label extension of NOR-SWITCH, stable switched patients stayed on CT-P13, and stable patients on infliximab switched to CT-P13. Efficacy, safety, and immunogenicity were similar between the groups; however, the authors of the systematic review said that “low enrollment numbers precluded conclusive implications to be drawn.”

The other 2 RCTs on nonmedical switching were conducted wholly on patients with IBD. In these trials, similar efficacy, safety, and immunogenicity were reported between groups. However, the authors of the systematic review caution that our understanding of the details of these studies is incomplete because they were presented at conferences and have yet to be published, a concern Scott echoes in his editorial.

The authors of the review acknowledge that, overall, the 21 published observational studies suggest that nonmedical switching from the infliximab originator to the biosimilar is safe, but they also note that study designs were heterogeneous and many lacked a control group. Loss of response and discontinuation rates also varied widely between studies. This variability in observational study design and results make it “difficult for broad generalizations regarding the safety and effectiveness of nonmedical [switching] to be made,” the authors noted, adding that observational studies have not had robust assessments for antidrug antibodies, leading to knowledge gaps regarding immunogenicity.

Mandatory switching to biosimilars to reduce health care costs and expand access to biologic therapies has been criticized by gastroenterologists, “who cite a lack of high-quality controlled trials to support such decisions in stable patients,” according to the review article. Several countries have instituted some measure of mandated switching to biosimilars, such as 

, and these policies have drawn criticism from 

. According to the editorial, “While nonmedical switching policies have been enacted, there has been incomplete pharmacovigilance reporting.”

Both the systematic review and accompanying editorial stress the need to ensure patient safety before cost reduction, as well as that future studies should address the knowledge gaps regarding long-term effectiveness and immunogenicity. They also recommend a greater reliance on published RCTs as opposed to those only available as conference abstracts.

Although the totality of the evidence is reassuring, the jury is still out on nonmedical switching to biosimilars, according to new study results.
 

Mark Campbell, PharmD

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