Maggie L. Shaw

Persons living with cancer, rheumatoid arthritis, or other conditions requiring costly biologic therapies may one day pay less for their medications—if a cascade of federal regulatory changes translates into meaningful market competition. 

Biosimilars make up just 5% of prescriptions in the US but accounted for 51% of total drug spending in 2024, and only about 10% of reference biologics that will lose patent protection in the next decade currently have a biosimilar in development. | Image credit: Tada Images - stock.adobe.com

On March 9, 2026, the FDA issued new draft guidance aimed at further reducing the time and expense of bringing biosimilars to market, the latest in a series of actions taken under the current administration to lower the cost of biologic drugs.

The draft guidance, titled "New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 4)," recommends streamlining unnecessary clinical pharmacokinetic (PK) testing when scientifically justified. 

PK studies evaluate how the body processes a drug and have traditionally been required as part of demonstrating that a biosimilar behaves like its reference product. The FDA stated this change could save biosimilar developers up to 50% of their PK study costs, or approximately $20 million per program.

The March guidance also revises how developers may use international data. Specifically, it provided updated recommendations to biosimilar applicants seeking to use data from a comparator product approved outside the US as evidence that a proposed product is biosimilar to the US-licensed product—describing scenarios in which a biosimilar applicant may use such clinical data without conducting an additional 3-way PK study involving the proposed biosimilar, the US-licensed reference product, and the non–US-licensed comparator.

In a related action, the FDA withdrew its 2015 final guidance on demonstrating biosimilarity to a reference product, stating it no longer represents the agency's current thinking.

The March announcement builds on a prior FDA effort in October 2025, when FDA Commissioner Marty Makary, MD, MPH, announced draft guidance reducing certain unnecessary comparative efficacy studies (CES), which can require 1 to 3 years and cost $24 million.

That earlier guidance drew wide attention for proposing a significant shift in how biosimilarity is demonstrated. The FDA emphasized that current analytical technologies offer sufficiently sensitive tools to characterize highly purified therapeutic proteins and, in many cases, can detect minor differences more precisely than a clinical trial.

 Under that framework, a well-conducted comparative analytical assessment (CAA) is often more sensitive than a CES, whose outcomes may be affected by factors such as dose selection, patient population variability, or trial design.

Weighing Market Urgency With Cautious Optimism

The urgency behind these actions is grounded in a stark spending imbalance. Biosimilars make up just 5% of prescriptions in the US but accounted for 51% of total drug spending in 2024, and only about 10% of reference biologics that will lose patent protection in the next decade currently have a biosimilar in development.

Congress established the approval pathway for biosimilars in 2010 through the Biologics Price Competition and Innovation Act, and the FDA has since approved 82 biosimilars, providing additional treatment options for conditions such as cancer, rheumatoid arthritis, diabetes, Crohn disease, and osteoporosis—although that figure represents a small fraction of approved biologics overall.

Industry stakeholders and patient advocates largely welcomed the October and March guidance. The Biosimilars Forum described the October guidance as addressing the affordability crisis in prescription medicines, and Makary emphasized that regulatory barriers have prevented greater biosimilar entry into the US market and that expanding competition is essential to driving down biologic prices and improving patient access.

Still, analysts and health policy experts cautioned against reading the regulatory changes as a near-term solution to drug costs.

Taking the New Guidance With a Grain of Salt

Regulatory streamlining addresses only one of several layers of friction slowing biosimilar uptake in the US. Even with lower development costs and shortened timelines, significant structural barriers remain. Manufacturers have shown hesitation to invest in biosimilars for small patient populations where return on investment is limited, manufacturing complexity for advanced biologics continues to require specialized facilities and expertise, and even with streamlined guidance, bringing a biosimilar to market can take nearly a decade.

Patent protections pose a particularly stubborn challenge. A GlobalData health care analyst noted that branded biologics will still control the market through patents, which act as a bottleneck to market entry for biosimilars, meaning the guidance will not, on its own, improve patient access to biosimilars.

The guidance has also attracted pushback from organizations focused on biologic safety. The Alliance for Safe Biologic Medicines submitted comments to the FDA expressing strong concern over what it characterized as the "genericizing" of biosimilars, stating that the proposed shifts would be "scientifically inappropriate and potentially harmful to patient confidence" and urging the agency to regulate in a manner consistent with the recognition that biosimilars are not generics.

Without additional reforms—such as addressing rebate structures, patent thickets, prescriber incentives, biosimilar education gaps, and pharmacy benefit manager transparency—the US may not realize the full potential of biosimilar competition.

 The benefits of these regulatory reforms could take years to materialize, underscoring that policy change alone will not close the biosimilar access gap.

The FDA is accepting public comments on the March 9 draft guidance, and developers and payers alike are expected to weigh in before the guidance is finalized.

FDA takes further steps to streamline biosimilar development and make medicines more affordable. News release. FDA. March 9, 2026. Accessed March 9, 2026. 

https://www.fda.gov/news-events/press-announcements/fda-takes-further-steps-streamline-biosimilar-development-and-make-medicines-more-affordable

Jeremias S. FDA guidance to remove one of the largest barriers to biosimilar development. 

. October 29, 2025. Accessed March 9, 2026. 

https://www.ajmc.com/view/fda-guidance-to-remove-one-of-the-largest-barriers-to-biosimilar-development

Jeremias S. A closer look at new FDA guidance removing barriers to biosimilar development. The Center for Biosimilars

. October 30, 2025. Accessed March 9, 2026. 

https://www.centerforbiosimilars.com/view/a-closer-look-at-new-fda-guidance-removing-barriers-to-biosimilar-development

Jeremias S. The biosimilar void: 90% of biologics coming off patent will lack biosimilars. The Center for Biosimilars. February 5, 2025. Accessed March 9, 2026. 

https://www.centerforbiosimilars.com/view/the-biosimilar-void-90-of-biologics-coming-off-patent-will-lack-biosimilars

The Center for Biosimilars. Biosimilar approvals. Updated December 22, 2025. Accessed March 9, 2026. 

https://www.centerforbiosimilars.com/biosimilar-approvals

Allen AK. FDA looks to simplify biosimilar development with new draft guidance. Clinical Trials Arena. October 30, 2025. Accessed March 9, 2026. 

https://www.clinicaltrialsarena.com/news/fda-biosimilar-approval-draft-guidance-2025

Worcester S. FDA aims to streamline biosimilar drug development. Medscape. November 21, 2025. Accessed March 9, 2026. 

https://www.medscape.com/viewarticle/fda-aims-streamline-biosimilar-drug-development-2025a1000whe

Articles

Biologics eat 51% of drug spending despite being 5% of prescriptions, but the FDA's new draft guidance hopes more competition can close that gap.

FDA Issues Draft Guidance Aimed at Cutting Expenses for Biosimilar PK Studies

More than €787 million was spent on omalizumab across 23 European countries in 2024 alone, underscoring the fiscal pressure associated with biologic treatment of severe allergic diseases.

 projected that the introduction of an omalizumab biosimilar could generate substantial savings for public payers over the next 5 years, with the potential to expand access to tens of thousands of additional patients.

Budget impact analysis finds omalizumab biosimilars in Europe could cut payer costs by €641M in 5 years, expanding access and driving major omalizumab savings. | Image credit: vadish - stock.adobe.com

Omalizumab, marketed as Xolair, is indicated for individuals with severe persistent allergic asthma, chronic spontaneous urticaria (CSU), and chronic rhinosinusitis with nasal polyps (CRSwNP). Although results from clinical trials have demonstrated reductions in exacerbations and improvements in quality of life, acquisition costs remain high. In the UK, annual treatment costs have ranged from £1664 to £26,624 depending on weight-based dosing.

 Across Europe, access has been constrained in some countries because of reimbursement restrictions and cost-effectiveness concerns.

To estimate the financial implications of biosimilar entry following patent expiry in September 2025, investigators developed a 5-year budget impact model from the payer perspective. The model compared a “world without biosimilars,” in which only originator omalizumab was available, with a “world with biosimilars,” in which a lower-cost biosimilar gradually captured market share. Twenty-three countries were included: Austria, Belgium, Bulgaria, Croatia, the Czech Republic, Finland, France, Germany, Greece, Hungary, Italy, Latvia, Lithuania, Luxembourg, Norway, Poland, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, and the UK. Countries were selected based on formulary listing, publicly available pricing, and IQVIA volume data.

Drug acquisition costs were derived from national list prices. The base-case analysis assumed that the biosimilar would enter the market at a 30% discount relative to the originator and that originator pricing would remain static—an assumption the authors noted likely underestimated real-world savings, as price erosion commonly occurs after biosimilar entry. Biosimilar uptake was modeled using adalimumab biosimilar adoption as a proxy, and omalizumab volume growth was extrapolated using historical compound annual growth rates between 2021 and 2024.

Under the 30% discount scenario, the model projected first-year savings of approximately €40 million across the 23 countries. Over 5 years, cumulative savings were estimated at €641 million. Germany was projected to realize the largest absolute savings—up to €130 million over 5 years—reflecting higher baseline utilization and spending. In contrast, countries with smaller populations or slower anticipated uptake, such as Luxembourg and Bulgaria, were projected to experience comparatively modest savings.

Investigators translated projected savings into potential access gains. Based on weighted average annual treatment costs across indications—48.37% for CSU, 44.77% for severe allergic asthma, and 6.86% for CRSwNP—the €641 million in cumulative savings could enable treatment of an estimated 96,491 additional patients over 5 years, assuming a full year of therapy per patient.

Sensitivity analyses examined deeper discount scenarios. At a 50% discount, cumulative 5-year savings were projected at approximately €1.04 billion, supporting treatment of an estimated 211,380 additional patients. At a 70% discount, savings increased to €1.44 billion, with the potential to treat up to 479,457 additional patients. Variations in market share uptake and overall market growth had comparatively modest effects on total savings, which ranged from €576 million to €703 million when uptake assumptions were varied by plus or minus 10%.

The authors acknowledged several limitations. The model did not use a prevalence-based approach because of inconsistent country-level epidemiologic data and limited information on treated populations by indication. Uptake projections relied on adalimumab biosimilar experience, which may not fully reflect prescribing behavior in allergic diseases. The analysis also excluded potential switching from other biologics and did not account for downstream cost offsets, such as reductions in hospitalizations or corticosteroid exposure. Administration costs were omitted under the assumption of therapeutic equivalence and similar delivery methods.

Despite these constraints, the analysis suggested that biosimilar entry could meaningfully alter the cost profile of omalizumab in Europe. By lowering acquisition costs, biosimilars may improve cost-effectiveness ratios and influence reimbursement decisions in settings where access has been limited. For payers managing constrained pharmaceutical budgets, the projected savings highlight the role biosimilars may play in expanding access to biologic therapy while moderating expenditure growth.

Jang M, Lee J, Kwon TS. Budget impact of introducing an omalizumab biosimilar in 23 European countries. 

2025;28(1);1639-1650. doi:10.1080/13696998.2025.2558450

Canonica GW, Colombo GL, Rogliani P, et al. Omalizumab for severe allergic asthma treatment in Italy: a cost-effectiveness analysis from PROXIMA study. 

. 2020;13:43-53. doi:10.2147/RMHP.S211321

Budget impact analysis finds omalizumab biosimilars in Europe could cut payer costs by €641M in 5 years, expanding access and driving major omalizumab savings.

Omalizumab Biosimilar Entry Linked to Expanded Patient Access, Reduced Spending

As biosimilars continue to replace originator biologics across Europe, clinicians and payers are increasingly looking to real-world data to confirm that large-scale switching strategies do not compromise patient safety. 

 from Denmark suggest that serious safety events remained uncommon among people with inflammatory arthritis treated with the infliximab biosimilar GP1111, including those who underwent biosimilar-to-biosimilar switching.

New Danish registry data confirm the safety of switching to infliximab biosimilars, showing low rates of serious adverse events in patients with inflammatory arthritis. | Image credit: Ilya - stock.adobe.com

The observational cohort study evaluated safety outcomes in routine clinical care among people with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or axial spondyloarthritis (axSpA) who initiated GP1111 between April 2019 and April 2022. Investigators used data from DANBIO, Denmark’s nationwide rheumatology registry, linked with national hospital, prescription, and mortality registries to capture serious adverse events during the first year of treatment.

Although randomized controlled trials have shown comparable safety profiles between infliximab biosimilars and the originator product, evidence has been more limited for biosimilar-to-biosimilar switching, particularly in heterogeneous, real-world populations. Denmark’s national treatment guidelines have mandated several infliximab switches over the past decade, creating an opportunity to evaluate safety outcomes across multiple switching scenarios.

 The authors noted that lingering concerns around immunogenicity and rare adverse events have contributed to clinician and patient hesitancy, underscoring the need for high-quality registry data.

The analysis included 2132 adults who initiated GP1111 during the study period. Of these, 1534 individuals (72%) had switched from another infliximab biosimilar, most commonly CT-P13. Participants were stratified into 5 mutually exclusive subcohorts based on prior biologic disease-modifying antirheumatic drug (bDMARD) exposure, including originator-experienced biosimilar switchers, originator-naïve biosimilar switchers, infliximab-experienced users, infliximab-naïve but bDMARD-experienced users, and bDMARD-naïve users.

Across indications, the median age ranged from the mid-40s to early 60s, and median disease duration ranged from 6 to 11 years. Approximately 23% of patients had at least 1 comorbidity at baseline, and 14% had used oral corticosteroids in the year prior to starting GP1111. Disease remission at baseline varied by diagnosis, occurring in 55% of people with RA, 54% of those with PsA, and 30% of those with axSpA.

During the 1-year follow-up period, serious safety events were infrequent across the overall cohort. Age- and sex-adjusted incidence rates per 100 person-years were 1.0 or lower for major adverse cardiovascular events (MACEs), venous thromboembolic events (VTEs), death, and severe allergic reactions.

A total of 19 MACE events were observed, corresponding to an adjusted incidence rate of 1.0 per 100 person-years. These events primarily occurred among older individuals, with a median age of 66 years. Venous thromboembolic events were rare, with 11 events recorded and an adjusted incidence rate of 0.6 per 100 person-years. Nine deaths occurred during follow-up, yielding an adjusted incidence rate of 0.6 per 100 person-years.

Severe allergic reactions were also uncommon, with 16 events reported. Although these reactions were observed more frequently among infliximab-naïve but bDMARD-experienced individuals, the overall adjusted incidence rate remained below 1.0 per 100 person-years.

Serious infections represented the most frequently observed adverse outcome. Fifty-eight serious infections requiring hospitalization were identified, corresponding to an adjusted incidence rate of 3.2 per 100 person-years in the overall cohort. Rates varied across treatment history subgroups, ranging from 2.1 to 5.6 per 100 person-years. In multivariable analyses, a history of serious infection prior to GP1111 initiation was associated with a higher risk of subsequent serious infection (HR, 2.06; 95% CI, 1.19-3.57). Other baseline factors, including prior biologic treatment history, were not significantly associated with infection risk.

The authors concluded that GP1111 demonstrated a favorable safety profile during the first year of treatment, regardless of prior infliximab or biosimilar exposure. They noted that serious infection rates were comparable to those previously reported for originator tumor necrosis factor inhibitors in similar populations.

Several limitations were acknowledged. The observational design precluded causal inference, and the low number of events limited the ability to adjust for multiple covariates or conduct detailed subgroup analyses for rare outcomes. Additionally, follow-up was limited to 1 year, and findings may not reflect longer-term safety. Nevertheless, the use of nationwide registries with near-complete coverage strengthened the reliability of event capture.

1. Nabi H, Jensen KY, Westermann R, et al. Safety outcomes in 2132 Danish patients with inflammatory arthritis treated with biosimilar infliximab (GP1111) in routine care. 

. Published online December 23, 2025. doi:10.1177/1759720X251393114

2. Nabi H, Hendricks O, Jensen DV, et al. Infliximab biosimilar-to-biosimilar switching in patients with inflammatory rheumatic disease: clinical outcomes in real-world patients from the DANBIO registry. 

. 2022;8(2):e002560. doi:10.1136/rmdopen-2022-002560

New Danish registry data confirm the safety of switching to infliximab biosimilars, showing low rates of serious adverse events in patients with inflammatory arthritis.

Danish Registry Analysis Finds Consistent Safety After Switching to Infliximab Biosimilar GP1111

Stakeholders across the US health care system navigated a maturing biological market that reached a significant milestone of 90 total approvals by the end of 2025.

 This progress, detailed in a recent industry report from Samsung Bioepis, highlighted how the biosimilar sector moved beyond early-stage growth into a complex era of high market penetration and shifting financial incentives.

The US biosimilar market evolves with 90 approvals, significant price drops, and new PBM models enhancing access to cost-effective therapies. | Image Credit: © ipopba - stock.adobe.com

As of December 2025, the FDA had cleared biosimilars for 20 unique biological molecules, with 63 of those 90 approvals (70%) successfully reaching the commercial market. These launches led to substantial price reductions over time; on average, the average sales price for biosimilars decreased by 52% within 5 years of the initial class launch. In more mature therapeutic areas, these price reductions reached as high as 77%.

Market adoption patterns revealed a distinct divide between "fast" and "slow" uptake markets. Oncology, ophthalmology, and pegfilgrastim biosimilars were categorized as fast-uptake products, achieving an average market share of 81% within 5 years of launch. In contrast, sectors such as immunology, filgrastim, and insulin glargine saw much slower adoption, averaging only a 25% market share in the same timeframe. By the third quarter of 2025, specific molecules like bevacizumab and trastuzumab reached biosimilar market shares of 92% and 88%, respectively.

Despite these gains, the industry faced significant issues regarding traditional pharmacy benefit management (PBM) contracting. Historically, the PBM model favored high-wholesale acquisition cost (WAC), high-rebate products because those products contributed more heavily to the "rebate guarantees" that PBMs promised to self-funded employers. This structure created a "rebate trap" where a lower-cost biosimilar might have a lower net price than the reference biologic but was excluded from formularies because it did not provide the necessary rebate volume to satisfy aggregate contractual guarantees.

In 2026, however, the report pointed to a critical shift toward fiduciary and transparent PBM models. These emerging frameworks prioritized trend management and cost control over rebate maximization. Some PBMs introduced "rebate credits," which allowed the price difference between a reference product and a biosimilar to count as a "phantom credit" toward rebate guarantees, effectively removing a major barrier to biosimilar adoption.

Thomas Newcomer, vice president and head of US commercial operations at Samsung Bioepis, commented on these systemic changes in the report's press release: “As the US healthcare market enters 2026, stakeholders’ approaches to prescription drug pricing and management continue to evolve. Alongside established PBM contracting structures, new models emphasizing alternative pricing reimbursement, transparency, and a shift towards more fiduciary responsibility have emerged in response to changing market conditions.”

Specific therapeutic areas also faced unique challenges as 2026 began.

 In the ophthalmology space, although 4 aflibercept biosimilar products are awaiting clearance to launch, the reference product faces only 1 competitor offering a 12% WAC discount. Meanwhile, the immunology sector saw a proliferation of complex pricing strategies; while private label brands became common for adalimumab and ustekinumab, most ustekinumab manufacturers avoided the dual "high WAC/low WAC" strategy that characterized the adalimumab market in previous years.

Looking forward through 2026, the continued erosion of reference product dominance appeared likely as PBMs pledged fuller rebate pass-throughs by 2028 and more employers adopted biosimilar-first strategies.

 These shifts suggested that the primary challenge for the industry was no longer demonstrating clinical parity but rather aligning financial incentives to ensure that the most cost-effective therapies reached the patient.

Biosimilar approvals. The Center for Biosimilars

. Updated December 22, 2025. Accessed January 27, 2026. 

SAMSUNG BIOEPIS: Biosimilar market report 12th edition, Q1 2026. January 23, 2026. Accessed January 27, 2026.

Samsung Bioepis releases Q1 2026 US biosimilar market report. News release. Samsung Bioepis. January 23, 2026. Accessed January 27, 2026. 

https://www.samsungbioepis.com/en/newsroom/newsroomView.do?idx=531&currentPage=1

Jeremias S. Happy birthday adalimumab biosimilars: reflecting on the first year of US competition. The Center for Biosimilars. January 31, 2024. Accessed January 27, 2026. 

https://www.centerforbiosimilars.com/view/happy-birthday-adalimumab-biosimilars-reflecting-on-the-first-year-of-us-competition

The US biosimilar market evolves with 90 approvals, significant price drops, and new PBM models enhancing access to cost-effective therapies.

Milestone Approvals, Evolving PBM Models May Redefine the 2026 Biosimilar Landscape

Biosimilar competition was associated with meaningful reductions in out-of-pocket spending for patients with Medicare coverage receiving clinician-administered biologics, according to a new analysis of national claims data.

 The findings suggested that, unlike trends seen in commercially insured populations, lower biologic prices following biosimilar entry were more likely to translate into direct savings for Medicare beneficiaries.

Biosimilar competition significantly reduces out-of-pocket costs for Medicare patients, enhancing affordability for biologic therapies and improving access. | Image credit: digicomphoto - stock.adobe.com

, evaluated changes in annual out-of-pocket spending among Medicare Advantage enrollees who received 1 of 7 biologic drugs that later faced biosimilar competition. The analysis included filgrastim, infliximab, epoetin alfa, pegfilgrastim, bevacizumab, rituximab, and trastuzumab, which first encountered biosimilar competitors between 2013 and 2019.

The study was conducted amid ongoing questions about whether biosimilar-related price reductions meaningfully benefit patients. 

 among commercially insured populations found that out-of-pocket costs did not consistently decline after biosimilar entry, largely because patient cost sharing is often based on negotiated reimbursement rates rather than drug prices.

 In contrast, Medicare reimbursement for clinician-administered biologics is closely tied to average sales prices, raising the possibility that biosimilar competition could more directly reduce patient spending.

Using Optum’s deidentified Clinformatics Data Mart Database, the investigators identified 273,774 patient-years from 2009 through 2022. Patients had a mean age of 76 years, 57.6% were female, and more than half received biologic therapies as part of cancer care. Nearly half of administrations occurred in outpatient clinics, and 13.0% of patient-years involved receipt of a biosimilar. Patients receiving low-income subsidies or who were dually eligible for Medicare and Medicaid were excluded because of their substantially lower cost-sharing requirements.

Across all 7 biologics, mean annual out-of-pocket spending declined after biosimilar competition began. In the composite analysis, adjusted mean annual spending decreased by $94, from $233 in the year before biosimilar entry to $165 by 4 years after competition. Declines were observed for each drug, although the magnitude varied. Rituximab was associated with the largest reduction, while filgrastim showed the smallest change.

The proportion of patient-years with zero out-of-pocket costs remained stable at approximately 41% before and after biosimilar entry, indicating that savings were concentrated among patients who already incurred cost sharing. Among patient-years with nonzero out-of-pocket spending, mean annual costs declined by $163 over the 4-year postcompetition period.

Reductions were most pronounced among patients who paid coinsurance or deductibles, whose cost sharing is directly tied to drug prices. In this group, mean annual out-of-pocket spending decreased by nearly $200 after biosimilar competition. By contrast, patients who paid only flat copayments did not experience significant changes in out-of-pocket costs, a finding consistent with the structure of fixed-fee cost sharing.

Sensitivity analyses showed that reductions in out-of-pocket spending occurred across most of the spending distribution, with the largest absolute decreases among patients with higher baseline costs. Trends in Medicare average sales prices mirrored these findings, with prices for originator biologics generally declining after biosimilar entry while biosimilar prices remained lower and continued to decrease over time.

The authors noted several limitations. Claims data did not capture manufacturer assistance programs, which may have led to overestimation of patient spending. The analysis was limited to Medicare Advantage enrollees and may not generalize to patients in traditional fee-for-service Medicare. Changes in plan design over time could also have influenced out-of-pocket costs independently of biosimilar competition. Additionally, the findings were specific to clinician-administered biologics and do not apply to pharmacy-dispensed biologics covered under Medicare Part D.

Overall, the results suggested that biosimilar competition was associated with lower out-of-pocket spending for Medicare patients, particularly for those whose cost sharing reflected drug prices. The findings highlighted the potential for timely biosimilar entry and sustained competition to improve affordability and access to biologic therapies for older adults.

Riegler JS, Kesselheim AS, Rome BN. Out-of-pocket spending for biologic drugs after biosimilar competition for Medicare patients. 

. 2026;9(1):e2554235. doi:10.1001/jamanetworkopen.2025.54235

. Updated December 22, 2025. Accessed January 21, 2026. 

Feng K, Russo M, Maini L, et al. Patient out-of-pocket costs for biologic drugs after biosimilar competition. 

. 2024;5(3):e235429. doi:10.1001/jamahealthforum.2023.5429

Biosimilar competition significantly reduces out-of-pocket costs for Medicare patients, enhancing affordability for biologic therapies and improving access.

Biosimilar Competition Linked to Lower Out-of-Pocket Costs for Medicare Patients

As biosimilars move into broader therapeutic areas, osteoporosis has emerged as a key test case for demonstrating equivalence in both bone density outcomes and safety.

Denosumab biosimilars enhance treatment access for postmenopausal osteoporosis, demonstrating equivalent efficacy and safety to reference products in recent trials. | Image credit: Lamina - stock.adobe.com

With 9 and 10 pairs of denosumab biosimilars approved in the US and European Union, respectively, lower-cost biologic alternatives to Prolia and Xgeva (reference denosumab) are increasingly shaping treatment access in osteoporosis, where long-term adherence is essential to prevent fractures and downstream costs.

In a recent randomized phase 3 trial, investigators addressed persistent cost and access barriers associated with denosumab, a monoclonal antibody that inhibits receptor activator of nuclear factor-κB ligand (RANKL) and is widely used for fracture risk reduction.

 Although denosumab has demonstrated durable efficacy and an acceptable long-term benefit–risk profile, its biologic pricing has limited uptake in some settings. Biosimilars are intended to expand access while maintaining equivalent clinical performance, a requirement emphasized by both the FDA and the European Medicines Agency.

The multicenter, double-blind study enrolled women aged 60 to 90 years with postmenopausal osteoporosis across 76 sites in Europe and the US between 2021 and 2023. Participants were randomized 1:1 to receive either the proposed biosimilar RGB-14-P or reference denosumab at a dose of 60 mg administered subcutaneously every 6 months, with follow-up through 52 weeks. All participants also received daily calcium and vitamin D supplementation.

A total of 473 participants were randomized and treated (n = 242 assigned to RGB-14-P and 231 to reference denosumab), and more than 92% completed the 52-week main study period. At baseline, the mean age was 66.7 years, and nearly all participants were White. Mean lumbar spine bone mineral density (BMD) T-scores were approximately −3.0 in both groups, consistent with established osteoporosis. Around 10% of participants in each arm had experienced a fracture within the year prior to enrollment.

The trial included 2 co-primary end points designed to satisfy regulatory expectations for biosimilar equivalence: percentage change from baseline in lumbar spine BMD at week 52 and area under the effect curve for percentage change in serum C-terminal telopeptide of type 1 collagen (CTX) through week 26. Both end points met prespecified equivalence margins.

At week 52, the adjusted mean increase in lumbar spine BMD was 4.89% in the biosimilar group and 4.55% in the reference denosumab group, yielding an estimated between-group difference of 0.34 percentage points (95% CI, −0.40 to 1.09), well within the equivalence margin of ±1.45%. Analyses required by US regulators also demonstrated noninferiority and nonsuperiority of the biosimilar relative to the reference product.

Pharmacodynamic outcomes mirrored these findings. The geometric mean ratio for the CTX area-under-the-curve end point was 1.01 (95% CI, 0.98-1.05; 

 = .49), confirming equivalent suppression of bone resorption. Secondary efficacy end points, including changes in total hip and femoral neck BMD at weeks 26 and 52, did not differ significantly between treatment arms.

Fracture outcomes, although not powered as primary end points, were similar across groups. By week 52, vertebral fragility fractures occurred in 1.7% of participants receiving RGB-14-P and 3.5% of those receiving reference denosumab, while nonvertebral fragility fractures occurred in 1.7% and 4.3%, respectively. Investigators noted that the overall fracture incidence was low, a common limitation in osteoporosis trials of relatively short duration.

Immunogenicity rates were low and comparable. Binding antidrug antibodies were detected in fewer than 1% of participants in either group, and neutralizing antibodies were identified in 0.4% of participants in each arm. Safety profiles were also similar, with approximately two-thirds of participants in each group experiencing at least 1 treatment-emergent adverse event. The most commonly reported events included infections such as COVID-19 and nasopharyngitis, hypocalcemia, headache, and arthralgia. Serious adverse events were uncommon and balanced between groups.

Investigators emphasized that the findings align with regulatory standards for biosimilar development. They wrote that the biosimilar “demonstrated equivalent efficacy and pharmacodynamics and similar immunogenicity and safety” compared with reference denosumab, adding that the results support its ability to “replicate the therapeutic benefit” of the originator in clinical practice.

Several limitations were acknowledged. The study population lacked racial diversity, which may affect generalizability, and follow-up was limited to 1 year, precluding assessment of longer-term fracture outcomes. Additionally, low fracture event rates constrained conclusions regarding comparative fracture prevention, although BMD changes are an accepted surrogate end point for regulatory decision-making.

From a managed care perspective, the results add to a growing body of evidence supporting denosumab biosimilars as clinically comparable options that may reduce drug spending while preserving outcomes. If approved and priced competitively, RGB-14-P could provide payers and health systems with additional leverage to improve access and support sustained osteoporosis treatment adherence.

Biosimilars approvals. The Center for Biosimilars

. Updated December 22, 2025. Accessed January 15, 2026. 

Seefried L, Ferrari S, Páll D, et al. A randomised phase 3 study comparing the efficacy and safety of proposed denosumab biosimilar RGB-14-P and reference denosumab in women with postmenopausal osteoporosis. 

. 2025;36(12):2497-2507. doi:10.1007/s00198-025-07711-x

Denosumab biosimilars enhance treatment access for postmenopausal osteoporosis, demonstrating equivalent efficacy and safety to reference products in recent trials.

Trial Data Support Equivalence of Denosumab Biosimilar in Postmenopausal Osteoporosis

Access to tumor necrosis factor inhibitors has expanded rapidly across Europe over the past decade, yet lingering questions about whether people can safely and effectively switch from reference biologics to biosimilars have continued to shape prescribing behavior.

 These questions have been especially prominent for etanercept, one of the earliest and most widely used biologic disease-modifying antirheumatic drugs, as health systems have sought savings without compromising outcomes for people living with chronic inflammatory diseases.

Explore the safety and efficacy of switching to etanercept biosimilars, backed by clinical trials and real-world evidence for chronic inflammatory diseases. | Image credit: peterschreiber.media - stock.adobe.com

To address these concerns, investigators conducted a narrative literature review evaluating clinical trial and real-world evidence on switching between reference etanercept and its approved biosimilars.

 The review was a response to persistent variability in biosimilar uptake across countries, which has been driven in part by clinician and patient uncertainty around switching, concerns about immunogenicity, and fears of loss of efficacy or increased adverse events. The authors aimed to synthesize available data to support informed decision-making for clinicians, payers, and people receiving treatment.

The review included evidence from 18 original studies identified through a PubMed search conducted in November 2024. Four were randomized, double-blind phase 3 clinical trials, and 14 were real-world observational studies. The studies evaluated switching from reference etanercept to biosimilars such as SB4, SDZ-ETN, LBEC0101, and YLB113 across multiple indications, including rheumatoid arthritis (RA), psoriatic arthritis, axial spondyloarthritis (AxSpA), plaque psoriasis, and juvenile idiopathic arthritis.

Across the controlled clinical trials, 1091 patients were included in switching populations. Of these, 769 had RA and 531 had plaque psoriasis, reflecting the primary indications studied in phase 3 programs. Trial designs varied, but all compared outcomes among people who continued reference etanercept or a biosimilar with those who switched treatments, typically at week 24 or week 52. One study, EGALITY, specifically evaluated multiple switches between reference etanercept and SDZ-ETN in people with moderate to severe plaque psoriasis.

Efficacy outcomes were consistent across trials. In RA populations, changes in disease activity scores such as DAS28-CRP and DAS28-ESR from baseline through follow-up were similar between continuous-treatment and switched groups. Proportions of patients achieving American College of Rheumatology 20%, 50%, or 70% response criteria and European Alliance of Associations for Rheumatology good or moderate responses were also comparable. In plaque psoriasis, mean changes in Psoriasis Area and Severity Index scores and response rates through 52 weeks did not differ meaningfully between those who underwent multiple switches and those who remained on a single product.

Safety findings from clinical trials showed no increase in treatment-emergent adverse events or serious adverse events following a switch. The proportion of patients experiencing at least 1 adverse event was similar between switched and nonswitched groups across indications. Immunogenicity rates were low overall, and antidrug antibodies were infrequently detected, with no consistent differences attributable to switching.

Real-world evidence reinforced these findings. Observational studies drawn from national registries and multicenter cohorts included thousands of patients across Europe and Canada. The studies captured broader and more heterogeneous populations compared with clinical trials, including people with long disease duration, multiple comorbidities, and prior biologic exposure. In these settings, disease activity measures generally remained stable following nonmedical switching from reference etanercept to a biosimilar. Rates of treatment discontinuation and serious adverse events were comparable to those observed before switching, although some cohorts reported higher discontinuation driven by subjective complaints rather than objective loss of efficacy.

Patient demographics varied widely across real-world studies but were representative of routine clinical practice. Most cohorts included adults with established inflammatory rheumatic disease, with mean ages typically in the fifth or sixth decade of life. Women were overrepresented in RA populations, while AxSpA cohorts included a higher proportion of men. Prior duration of etanercept use ranged from several months to multiple years before switching.

The authors noted several limitations. The review was narrative rather than a formal meta-analysis, and the included studies differed in design, outcomes measured, and length of follow-up. Evidence on multiple switches between different biosimilars was limited, and patient-reported outcomes were not consistently assessed. Most real-world data came from European health systems with established biosimilar policies, which may limit how well the findings apply to other regions.

The review found no evidence that switching between reference etanercept and its biosimilars adversely affected efficacy, safety, or immunogenicity across approved indications. The authors concluded that the accumulated clinical and real-world evidence supported broader adoption of etanercept biosimilars, while underscoring that “these gaps in the literature warrant further research efforts to better understand the long-term effects of biosimilar switching and to develop strategies to optimize patient outcomes.”

1. Mestre-Ferrandiz J, Czech M, Smolen JS, et al. Capturing the holistic value of biosimilars in Europe – part 1: a historical perspective. 

. 2024;24(2):237-250. doi:10.1080/14737167.2023.2297926

2. Biosimilar approvals. The Center for Biosimilars

. Updated November 12, 2025. Accessed January 5, 2026. 

3. Schmalzing M, Askari A, Girolomoni G, Perez-Coleman JCV. Salvati C, Bachinskaya E. Clinical and real-world evidence on etanercept biosimilar switching: a narrative literature review of efficacy and safety. 

. Published online November 18, 2025. doi:10.1007/s12325-025-03367-5

Explore the safety and efficacy of switching to etanercept biosimilars, backed by clinical trials and real-world evidence for chronic inflammatory diseases.

Evidence Supports Safe, Effective Switching to Etanercept Biosimilars

The US biosimilar market officially capped off a high-stakes year for regulatory activity with a final expansion in the denosumab space. The FDA approved 2 new biosimilars from Amneal Pharmaceuticals, Boncresa (denosumab-mobz) and Oziltus (denosumab-mobz), which serve as lower-cost alternatives to the reference biologics Prolia and Xgeva, respectively.

 This move concluded a busy 12 months for the industry, marking the eighth pair of denosumab biosimilars—the ninth pair overall—to receive approvals in 2025.

The flurry of 2025 approvals aligned with the FDA’s ongoing effort to modernize the biosimilar pathway by prioritizing advanced analytical data over repetitive clinical trials. | Image Credit: gguy - stock.adobe.com

A Strategic Partnership for Market Growth

Amneal’s latest approvals were the result of a collaboration with mAbxience, a group majority-owned by Fresenius Kabi.

 Although mAbxience handled the development and manufacturing of the products, Amneal held the exclusive rights for commercialization in the US. This launch brought Amneal’s commercial biosimilar portfolio to 5 products, moving the company closer to its goal of having 6 biosimilars across 8 presentations by 2027.

The entry of Boncresa and Oziltus was particularly significant for managed care stakeholders given the market size of the reference products. As of October 2025, annual US sales for Prolia and Xgeva reached approximately $5.3 billion, highlighting the massive potential for savings as competition intensified.

Closing Out a "Banger Year" for Denosumab

The denosumab landscape saw a rapid influx of products throughout the fall, making the year-end Amneal announcement the final piece of a much larger puzzle. In September, the FDA cleared Hikma Pharmaceuticals’ and Gedeon Richter’s Enoby and Xtrenbo, followed closely by Accord Healthcare’s October approvals for Osvyrti and Jubereq.

The market further evolved in late October when the FDA granted interchangeability (IC) designations to 2 pairs of denosumab products. Fresenius Kabi’s Conexxence and Bomyntra were the first to receive this status, followed by Celltrion’s Stobocclo and Osenvelt. These designations were supported by clinical data from postmenopausal women with osteoporosis, proving that switching between the biosimilar and the reference product did not result in clinically meaningful differences in safety or efficacy.

While 2025 was a win for access, it was also a year of policy-related questions. Federal officials, including HHS Secretary Robert F. Kennedy Jr. and FDA Commissioner Marty Makary, MD, sparked an industrywide discussion by suggesting that all biosimilars should be considered interchangeable with their reference products to simplify the substitution process.

 Despite these statements, the FDA continued to issue formal IC designations based on statutory requirements, leaving some uncertainty regarding how state laws on automatic pharmacy substitution would eventually align with federal guidance.

For health care providers, the new biosimilars brought the same clinical responsibilities as the original biologics. The FDA required that both Boncresa and Oziltus be administered by a professional, with a focus on monitoring serum calcium levels. Patients with advanced chronic kidney disease remained under a boxed warning for severe, life-threatening hypocalcemia, and clinicians were reminded to rule out pregnancy before starting treatment.

The reported adverse events continued to reflect the diverse needs of the treated populations. Men receiving treatment frequently experienced joint pain and back pain, while postmenopausal women were more likely to report musculoskeletal pain and cystitis. In the oncology space, patients with bone metastases often reported nausea and fatigue, while individuals with multiple myeloma frequently dealt with anemia and gastrointestinal issues.

The flurry of 2025 approvals aligned with the FDA’s ongoing effort to modernize the biosimilar pathway by prioritizing advanced analytical data over repetitive clinical trials. This evolution was intended to lower development costs—which historically reached between $100 million and $300 million—and speed up the arrival of new competitors.

However, experts warned that the industry still faces a "biosimilar gap." Only about 10% of biologics expected to lose exclusivity in the next decade have biosimilars currently in development. As Amneal’s new products entered the market, the focus shifted toward whether payer incentives and pharmacy benefit manager transparency would allow these new entries to reach their full potential for cost savings. For now, the successful conclusion of the denosumab approval cycle served as a milestone in the long-term push for affordable medicine in the US.


1. Amneal announces FDA approval of denosumab biosimilars referencing Prolia and Xgeva. News release. Amneal Pharmaceuticals. December 22, 2025. Accessed January 5, 2026. 

https://investors.amneal.com/news/press-releases/press-release-details/2025/Amneal-Announces-FDA-Approval-of-Denosumab-Biosimilars-Referencing-Prolia-and-XGEVA

3. FDA quietly approves denosumab biosimilars, issues interchangeability for others. The Center for Biosimilars. November 13, 2025. Accessed January 4, 2026. 

https://www.centerforbiosimilars.com/view/fda-quietly-approves-denosumab-biosimilars-issues-interchangeability-for-others

FDA approves new denosumab biosimilars, enhancing treatment options for osteoporosis and bone metastases while driving competition and cost savings.

FDA Approves Amneal Denosumab Biosimilars, Capping Year of Market Expansion

FDA approves Celltrion's Eydenzelt, a new aflibercept biosimilar, enhancing treatment options for retinal diseases in the US. | Image credit: Tada Images - stock.adobe.com

The FDA has approved Eydenzelt (aflibercept-boav), an aflibercept biosimilar developed by Celltrion to reference Eylea (aflibercept), an anti–vascular endothelial growth factor used to treat retinal diseases.

The American approval comes after the same biosimilar received marketing authorization from the European Commission in February 2025.

"Timely access to effective therapies is essential for individuals affected by retinal diseases. We are proud to have Eydenzelt approved by the FDA, and we look forward to expanding the availability and access of biological treatments across the US," said Juby Jacob-Nara, PhD, senior vice president and chief medical officer at Celltrion USA.

 "With Eydenzelt demonstrating biosimilarity to its reference product, we believe this approval will mark a significant milestone in the treatment landscape of retinal diseases—helping physicians broaden their options and improving patient outcomes."

Aflibercept products are administered intravitreally in a physician's office and are designed to block the growth of new blood vessels and decrease vascular permeability in the eye, 2 factors involved in ocular angiogenesis.

Eydenzelt is approved for the treatment of neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema (DME), and diabetic retinopathy.

The FDA based its approval on a totality of evidence, including analytical, nonclinical, and clinical data.

In a randomized, double-masked, parallel-group, multicenter phase 3 study, the efficacy, safety, pharmacokinetics, and immunogenicity of Eydenzelt were compared with Eylea in patients with DME. 

The primary end point was the change in best corrected visual acuity from baseline to week 8, comparing Eydenzelt with Eylea. The 52-week trial enrolled 348 patients with DME. Results showed that Eydenzelt met the predefined equivalence criteria, and secondary end points related to efficacy, safety, and immunogenicity demonstrated trends consistent with those observed for Eylea.

Eydenzelt represents Celltrion’s first FDA-approved biologic product in ophthalmology. It is also the sixth aflibercept approval in the US, following the FDA's authorizations of Pavblu (aflibercept-ayyh), Enzeevu (aflibercept-abzv), Ahzantive (aflibercept-mrbb), Yesafili (aflibercept-jbvf), and Opuviz (aflibercept-yszy).

Celltrion receives U.S. FDA approval for Eydenzelt (aflibercept-boav), biosimilar referencing Eylea (aflibercept). News release. Celltrion. October 9, 2025. Accessed October 13, 2025. 

https://www.celltrion.com/en-us/company/media-center/press-release/4201

Jeremias S. EC approves Celltrion denosumab, aflibercept biosimilars. The Center for Biosimilars

The FDA has approved Celltrion's Eydenzelt, a new aflibercept biosimilar, enhancing treatment options for retinal diseases in the US.