Do Changes Signal The End Of Biosimilar Regulatory Redundancy?

By Partha Anbil, MIT Sloan Life Sciences Industry Advisor

A revolution in biosimilar market dynamics promises to reshape competition and pricing for biologic therapies — a domain initially excluded from generic-style abbreviated pathways.

In June 2024, the FDA issued draft guidance proposing a fundamental change to interchangeability standards for biosimilars.¹ Historically, biosimilars could achieve "interchangeability" designation only through dedicated switching studies demonstrating that switching between reference products and biosimilars posed no safety or efficacy risks. This requirement created substantial development burdens and limited biosimilar adoption despite approval.

The 2024 draft guidance eliminates this requirement. Biosimilar developers can now demonstrate interchangeability through analytical and clinical comparability data already required for baseline biosimilar approval, without conducting additional switching studies.² This change directly addresses findings from the analysis of biosimilar switching data spanning 2022–2025, which show that patients who switch to biosimilars maintain high satisfaction and clinical stability. Humira-to-biosimilar transitions (Hadlima, Hyrimoz) showing similar clinical outcomes ³, ustekinumab biosimilar switches in IBD patients ⁴, and a Navitus study showing 94% of members successfully switched to a biosimilar within three months. A 2024 Association for Accessible Medicines report documents more than 2.7 billion days of patient therapy with biosimilars with no meaningful clinical differences.⁵

The EMA declared all biosimilars interchangeable in 2022, further supporting the safety of switching based on accumulated evidence — yet payers lacked policy frameworks to incentivize switching due to conservative FDA language around "biosimilarity" versus "interchangeability."

In October 2025, FDA released draft guidance further smoothing pathways to biosimilar approval by proposing to deprioritize comparative efficacy studies in exchange for more robust analytical data.⁶ In March 2026, the FDA issued yet another draft guidance proposing major updates to biosimilar pharmacokinetic (PK) study requirements, further reducing the time and expense of bringing biosimilars to market.⁷ The move aligns with the evolution happening abroad. In a reflection paper, the EMA called for a reevaluation of the need to perform comparative efficacy studies, at least for "some less complex biologicals with a straightforward mechanism of action."⁸

Market Momentum: Record 2024–25 Approvals

The regulatory shift coincides with unprecedented market activity:

• FDA approved 18 biosimilars in 2024, the highest annual total at the time.⁹
• In 2025, the FDA approved an additional 26 biosimilars, a new record surpassing the 18 approved in 2024, bringing the cumulative total to 90 biosimilars approved through the 351(k) pathway. Notable 2025 approvals include eight denosumab biosimilars, the first interchangeable omalizumab biosimilar (Omylclo), and Kirsty, the first interchangeable rapid-acting insulin aspart biosimilar.⁹
• The EMA approved a record 44 biosimilars in 2025 (the highest annual number ever), up from 28 in 2024¹⁰, with denosumab biosimilars representing the single largest category (12 approvals for Prolia/Xgeva indications).
• As of early 2026, the EMA has authorized approximately 152 total biosimilars, excluding withdrawn products.¹⁰

Recent approvals target significant commercial opportunities:

Immunology: Biosimilars of Stelara (ustekinumab) have entered the market, addressing one of the most-prescribed biologics in dermatology and gastroenterology. Stelara biosimilars entered the US market in 2025 with discounts of up to 85%, and real-world switching data from the European Crohn's and Colitis Organization congress in February shows successful transitions for IBD patients. Early 2025 approvals in this category suggest intensifying competition in the TNF-inhibitor and IL-12/IL-23 inhibitor segments.

Oncology: Biosimilars of Keytruda (pembrolizumab) are in development, with multiple candidates advancing through clinical trials in 2026–27. Formycon reported positive PK data for its candidate FYB206 in February 2026, targeting a BLA filing by mid-2027. First US approvals and market launches are anticipated in 2028–29 following key patent expirations in late 2028. This represents the first significant wave of oncology immune checkpoint biosimilars, with profound implications for cancer care access and costs. Oncology biosimilars are already on the market achieving strong uptake: the Cardinal Health 2026 Biosimilars Report finds that oncology biosimilars reach an average 81% market share within five years of launch.

As of Q1 2026, no Keytruda biosimilar has been approved in the United States. Keytruda's primary US patents expire in late 2028 (with extensions to 2029), and its 12-year regulatory exclusivity expires on September 4, 2026.

 Amgen, Henlius (IND cleared Sep 2025), and other companies have pembrolizumab biosimilar candidates in their pipelines. Bioéticos launched the first pembrolizumab biosimilar globally in Paraguay in August 2025, but this is not a US-approved product.

Endocrinology: Biosimilars for Trulicity (dulaglutide), a GLP-1 receptor agonist, are advancing with FDA decisions anticipated in early-to-mid 2026. The GLP-1 landscape has evolved markedly: as of Q1 2026, semaglutide supply has stabilized (70–85% availability) and tirzepatide availability has reached approximately 85–90% following expanded manufacturing. The approval of oral semaglutide (Wegovy) for weight loss and pending FDA decisions on tirzepatide for cardiovascular outcomes are reshaping the competitive environment into which dulaglutide biosimilars will enter.

Clinical Trial and IRB Review Regulatory Modernization

Beyond accelerated approval and biosimilar pathways, broader clinical trial regulations are transforming to address long-standing inefficiencies and modernize evidence generation.

The FDA is harmonizing guidance on single institutional review board (IRB) reviews for multicenter clinical trials, replacing the previous system where each trial site maintained independent IRB review.² Single IRB review will reduce duplicative review cycles, accelerate trial initiation, and simplify sponsor compliance while maintaining ethical oversight. Implementation is expected to expedite trial startup timelines by 20%-30%, directly supporting accelerated approval programs' goal of faster confirmatory trial execution.

Real-World Evidence and AI Integration

The FDA's Advancing Real-World Evidence (RWE) Program increasingly leverages patient registries, electronic health records, and observational data to support regulatory decisions.² This shift is particularly relevant for confirmatory trials in accelerated approval programs, where RWE can supplement traditional trials to demonstrate clinical benefit on patient-relevant outcomes.

Example: Diverse participant enrollment requirements

Following the 2022 FDA draft guidance on Diversity Plans and the 2023 Food and Drug Omnibus Reform Act (FDORA), which requires diversity action plans, regulatory scrutiny of trial demographics has intensified. Analysis of FDA-approved oncology trials from 2017-24 reveals persistent underrepresentation of Black participants (typically 8%-12% of participants vs. ~13% of the population) and suboptimal female enrollment in trials that allow both genders (24%-47% of participants vs. 50% expected).²

The CDER 2026 guidance agenda includes "Collection of Race and Ethnicity Data in Clinical Trials and Clinical Studies for FDA-Regulated Medical Products: Revised Draft," signaling continued regulatory emphasis on representative enrollment. The FDA will increasingly condition approval on demonstrated efforts to achieve representative enrollment, affecting trial design timelines and site selection strategies.

Accelerated Approval Portfolio Implications

Pre-approval trial initiation: Companies pursuing accelerated approval must now plan confirmatory trial infrastructure in parallel with pre-approval trial conduct, increasing development budgets by 15%-25% but substantially reducing post-approval timeline uncertainty. This favors larger companies with robust development infrastructure over smaller biotechs.

Surrogate endpoint selection: FDA's 2025 guidance provides clearer standards for acceptable surrogate endpoints but applies higher scrutiny to novel surrogates. Oncology programs relying on response rate and progression-free survival thresholds face lower risk; neurology programs targeting new biomarkers face higher uncertainty about endpoint acceptance. The FDA's March 2026 pharmacokinetic draft guidance reinforces the broader trend toward analytical primacy over clinical studies — a shift with implications for surrogate endpoint strategy across both accelerated approval and biosimilar programs.

Withdrawal risk management: Companies must plan for the possibility of accelerated approval withdrawal at the time of approval. Financial modeling should incorporate 10%-15% probability of indication withdrawal within 5 years for novel indications, substantially higher for programs where clinical benefit pathways are uncertain.

Biosimilar Development Opportunities

Interchangeability timing: The elimination of switching study requirements accelerates interchangeability timelines by two to four years and reduces costs by approximately $15 million - $30 million per program. The October 2025 and March 2026 FDA draft guidances further reduce development costs, with comparative efficacy studies alone costing $24 million on average and requiring one to three years. Companies with biosimilar candidates in the pipeline can realistically target interchangeability status by 2027–28, enabled by the streamlined regulatory framework.

Market entry sequencing: Second-to-market biosimilars entering within three years of first biosimilar approval demonstrate accelerated price reductions, with some molecules seeing 20% - 30% additional price drops annually. Companies should evaluate aggressive development timelines and parallel regulatory submissions to capture a second-mover advantage before pricing compression limits margins.

Therapeutic area focus: Immunology (TNF inhibitors, IL-12/IL-23 inhibitors), oncology (immune checkpoint inhibitors), and endocrinology (GLP-1 agonists) represent the highest-value opportunities through 2028, with orphan disease biosimilars offering lower competition but smaller revenue pools. The approaching patent cliff estimated at $236 billion in global brand sales at risk by 2030  including Keytruda ($29.5 billion revenue), Stelara ($6.72 billion), and Opdivo ($9 billion), represents an unprecedented wave of biosimilar development opportunities.¹¹ However, the IRA's Maximum Fair Price mechanism introduces a "biosimilar paradox, in which negotiated price floors may compress biosimilar margins, making development less viable for some molecules even as exclusivity expires.

Conclusion

The transformation of U.S. pharmaceutical regulation beginning in 2024 represents a critical inflection point in balancing access to innovation with patient protection. Biosimilar market dynamics are shifting from regulatory constraint to competitive intensity, promising substantial cost savings and expanded access to biologic therapies while reshaping the financial models of blockbuster originator products.

Industry professionals must navigate this environment by investing in robust confirmatory trial infrastructure, monitoring regulatory guidance releases and FDA enforcement patterns, and strategically evaluating biosimilar development opportunities across high-value therapeutic areas. Companies that proactively align with the heightened regulatory expectations of 2026–27 and capitalize on biosimilar market opportunities can succeed in an environment that demands both innovation and accountability.

References:

1. FDA. (2024, June 21) Considerations in Demonstrating Interchangeability With a Reference Product: Update
2. FDA. (2025-2026). Regulatory Updates in Clinical Trials and Biosimilar Development. Multiple guidance documents.
3. Pharmacy Times. (2025, December 17) Infliximab and Adalimumab Biosimilars Maintain Comparable Safety, Efficacy, Immunogenicity in IBD
4. Hospital Healthcare Europe. (2026, March) Biosimilars in IBD: key ustekinumab research from ECCO’26
5. Association for Accessible Medicines. (2024, September) Generic and Biosimilar Medicines Save $445 Billion in 2023
6. FDA. (2025, October 29). FDA Moves to Accelerate Biosimilar Development and Lower Drug Costs [news release].
7. FDA. (2026, March 9). Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations [draft guidance]
8. EMA. (2024, February) Concept paper for the development of a reflection paper on a tailored clinical approach in biosimilar development [news release]
9. FDA Biosimilar Product Information database, accessed 20 April, 2026
10.  JDSupra (2026, January) How the U.S. Compares to Europe on Biosimilar Approvals and Products In the Pipeline – Updated January 22, 2026

Editor's Note: The views expressed in the article are those of the authors and not of the organizations they represent.

About The Author:

Partha Anbil is at the intersection of the life sciences industry and management consulting. He is currently senior vice president of life sciences at Coforge Limited. He held senior leadership roles at WNS, IBM, Booz & Company, Symphony, IQVIA, KPMG Consulting, and PWC. He has consulted with and counseled health and life sciences clients on structuring solutions to address strategic, operational, and organizational challenges. He was a member of the IBM Industry Academy. He is a healthcare expert member of the World Economic Forum (WEF). He is also a life sciences industry advisor at MIT, his alma mater.