Skylar Jeremias is the Managing Editor for The Center for Biosimilars and The American Journal of Managed Care (AJMC).

Skylar Jeremias

At $150,000 per quality-adjusted life-year (QALY), biosimilar denosumab (Prolia; Amgen) clears the cost-effectiveness bar against every oral bisphosphonate and against zoledronic acid for postmenopausal women at high fracture risk—but drop the threshold to $100,000, and only 1 comparison holds up, according to a 

A Gap Left by Reference Denosumab Modeling

More than 2 million osteoporosis-related fractures occur annually in the US, with direct and indirect costs projected to climb from $57.0 billion in 2018 to more than $95.2 billion by 2040. Oral bisphosphonates remain first-line therapy for postmenopausal osteoporosis (PMO), yet roughly 70% of US patients receive no treatment

at all, largely due to poor compliance, gastrointestinal (

) adverse events (AEs), and high drug costs. Reference denosumab offers better adherence and convenience as a twice-yearly injection, but its price has nearly doubled since FDA approval, limiting affordability.

Sandoz's biosimilar denosumab, marketed in the US as Jubbonti (denosumab-bbdz), became the first FDA-approved denosumab biosimilar in March 2024 and launched commercially in June 2025, positioned by Sandoz as a lower-cost option intended to expand patient access.

 The economic question remained open, though: prior cost-effectiveness analyses evaluated reference denosumab against bisphosphonates, but none had assessed the biosimilar until a new cost-utility analysis took it on.

A Lifetime Markov Model From the Payer's Chair

The analysis modeled a hypothetical cohort of women with PMO at high fracture risk using an 8-health-state Markov model with a lifetime horizon and 6-month cycles, tracking patients from treatment initiation until death or age 99 years. The starting age of 72.3 years mirrored the mean age enrolled in the pivotal FREEDOM trial (

), which established reference denosumab's fracture-prevention efficacy. The model adopted a US payer perspective aligned with Medicare fee-for-service/Part B, counting only direct medical costs—drug acquisition, administration, disease monitoring, and fracture management—discounted at 3% annually.

Biosimilar denosumab was compared individually against alendronate, risedronate, ibandronate, and zoledronic acid; reference denosumab was excluded as a “dominated” comparator since the biosimilar was assumed to match its efficacy at a lower price. Because biosimilar denosumab's actual US price was not yet public at the time of modeling, the researchers estimated it at 80% of reference denosumab's cost, using Medicare pricing data and a 2022 Amgen biosimilar report. Treatment-effect estimates for hip, vertebral, wrist, and other osteoporotic fractures were drawn from published network meta-analyses.

ICERs Stayed Under $150,000, but Not Always Under $100,000

Biosimilar denosumab produced more QALYs than every bisphosphonate—0.043, 0.043, 0.042, and 0.030 additional QALYs per patient vs alendronate, risedronate, ibandronate, and zoledronic acid, respectively—at incremental costs of $4379, $4057, $4265, and $4390. The resulting incremental cost-effectiveness ratios (ICERs) were $101,017; $93,544; $100,515; and $144,995 per QALY gained, all of which fell under a willingness-to-pay threshold of $150,000 per QALY gained. Only the risedronate comparison cleared the more conservative $100,000 threshold outright; the alendronate and ibandronate comparisons missed it narrowly, and the zoledronic acid comparison missed it by the widest margin.

“As a lower-cost alternative to reference denosumab, biosimilar denosumab may enhance patient access to effective PMO treatment in the USA,” the researchers wrote.

A probabilistic sensitivity analysis of 1000 iterations reinforced that picture. At the $150,000 threshold, biosimilar denosumab was cost-effective in 100% of iterations against alendronate, risedronate, and ibandronate, but in only 55.4% of iterations against zoledronic acid. At the $100,000 threshold, it was cost-effective in 72.3% of iterations against risedronate, 29.9% against ibandronate, and 24.0% against alendronate, and not cost-effective against zoledronic acid.

Price and patient age were the 2 most influential drivers of the results. Dropping biosimilar denosumab's price to 40% of reference denosumab's cost pushed every ICER below $100,000 per QALY gained; at 20% of reference cost, the biosimilar dominated all 4 bisphosphonates—cheaper and more effective across the board. Starting age cut just as sharply: modeled ICERs ranged from roughly $164,000 to $215,000 per QALY gained at age 65 years but fell to $25,000 to $95,000 per QALY gained at age 85—the biosimilar's economic case strengthens in older, higher-risk patients and weakens in younger ones.

A Hypothetical Price, Built on Borrowed Data

The analysis carries meaningful caveats. Because biosimilar denosumab's US price was unknown at the time of modeling, the study's central estimate—a 20% discount to reference denosumab—was hypothetical, and the authors acknowledged that actual cost-effectiveness will depend on the biosimilar's real price. Jubbonti's June 2025 launch gives payers an actual contract price to test that assumption against as pricing data becomes available.

Other inputs relied on non-US data where domestic evidence was lacking, including a Swedish study for postfracture risk and multinational trials for AE rates, and the analysis excluded societal costs like productivity losses, consistent with its payer-only perspective.

For health plans weighing formulary strategy, biosimilar denosumab clears a reasonable value bar even before the price erosion typical of biosimilar markets sets in. Combined with denosumab's twice-yearly dosing and lower GI-related discontinuation, the economic case could support broader coverage for older, high-risk patients, where the model's ICERs were most favorable, while bisphosphonates may remain the more cost-effective first choice for younger postmenopausal women.

Flanigan J, Kane S, Mirzayeh Fashami F, et al. Cost-effectiveness of biosimilar denosumab versus bisphosphonates in postmenopausal osteoporosis. 

. 2026;10(4):733-748. doi:10.1007/s41669-026-00651-0

Jeremias S. Wyost and Jubbonti launch as first denosumab biosimilars in the US. 

. June 2, 2025. Accessed August 4, 2026. 

https://www.centerforbiosimilars.com/view/wyost-and-jubbonti-launch-as-first-denosumab-biosimilars-in-the-us

Articles

Biosimilar denosumab cleared a $150,000 per QALY cost-effectiveness threshold against bisphosphonates for high-risk PMO, but not always at $100,000.

Biosimilar Denosumab Shows Cost-Effectiveness Over Bisphosphonates in PMO

July brought continued momentum across the biosimilars landscape, from congressional efforts to strengthen market competition to new analytical and clinical data supporting biosimilar development. 

This monthly roundup highlights some of the month's biggest stories, including advances in biosimilar policy, proposed romosozumab and ustekinumab biosimilars, and the FDA's acceptance of Sandoz's generic tirzepatide applications.

Biosimilar Bills Advance in Congress, but Broader Reform Remains Unfinished

 aimed at improving biosimilar adoption, with several bipartisan bills advancing through committees this year. The proposals target issues such as reimbursement, regulatory efficiency, and patient access, signaling that biosimilars remain a priority for lawmakers.

Still, many of the policy changes stakeholders have long pushed for have yet to move forward. Reforms addressing pharmacy benefit manager practices, payment incentives, and broader market barriers remain absent, leaving questions about whether the current legislation will meaningfully increase biosimilar uptake on its own.

Romosozumab Biosimilar Matches Reference Despite Structural Differences

A proposed romosozumab biosimilar demonstrated comparable functional activity to the reference product despite small differences in disulfide bond patterns, according to 

Researchers found the structural differences did not affect target binding or other critical quality attributes, supporting biosimilarity. The findings highlight the importance of comprehensive analytical testing and add to the growing evidence supporting biosimilar development in osteoporosis, where fewer competitors are currently in the pipeline than in oncology or immunology.

FDA Accepts Sandoz Generic Tirzepatide Applications

The FDA has accepted Sandoz's abbreviated new drug applications for generic versions of tirzepatide, marking another milestone in the race to bring lower-cost alternatives to the blockbuster diabetes and obesity therapy.

Unlike monoclonal antibodies, tirzepatide is regulated as a peptide, making it eligible for the generic 

 rather than the biosimilar pathway. The applications also underscore a growing regulatory gap, as peptide-based medicines continue to blur the line between traditional generics and biologics.

Repeated Switching Data Support Biosimilar ABP 654

New data suggest patients can safely switch multiple times between ustekinumab and the investigational biosimilar ABP 654 without compromising efficacy, safety, or immunogenicity.

 add to a growing body of evidence supporting switching between reference biologics and biosimilars. As payers increasingly implement biosimilar-first policies, studies like this may help reassure clinicians who remain hesitant about repeated transitions during long-term treatment.

1. Jeremias S. Biosimilar bills gain steam in congress, but key reforms still wait. 

. July 23, 2026. Accessed July 31, 2026. 

https://www.centerforbiosimilars.com/view/biosimilar-bills-gain-steam-in-congress-but-key-reforms-still-wait

2. McCormick B. Romosozumab biosimilar matches reference in functional testing despite disulfide differences. 

. July 16, 2026. Accessed July 31, 2026. 

https://www.centerforbiosimilars.com/view/romosozumab-biosimilar-matches-reference-in-functional-testing-despite-disulfide-differences

3. Jeremias S. FDA accepts Sandiz generic tirzepatide applications amid biosimilar development gap. 

https://www.centerforbiosimilars.com/view/fda-accepts-sandoz-generic-tirzepatide-applications-amid-biosimilar-development-gap

4. Jeremias S. Biosimilar ABP 654 maintains efficacy, safety after repeated switching from ustekinumab. 

https://www.centerforbiosimilars.com/view/biosimilar-abp-654-maintains-efficacy-safety-after-repeated-switching-from-ustekinumab

Congress advances biosimilar bills as new data emerge on romosozumab, tirzepatide, and ustekinumab biosimilar development.

Biosimilars Round Up: July 2026

In the span of 8 days this July, lawmakers introduced a new biosimilar bill, advanced 2 others out of committee in both chambers, and left a longer list of related proposals unmoved for months.

US capitol | Image credit: W.Scott McGill - stock.adobe.com

A Bill Introduced, Marked Up, and Advanced Inside a Week

Representative Nick Langworthy (R, New York) and Representative Kim Schrier, MD (D, Washington), introduced the Expedited Access to Biosimilars Act (HR 9661) on July 15, 2026.

 The measure would codify that comparative clinical efficacy and pharmacodynamic studies are not the default expectation for biosimilar licensure, preserve the FDA's authority to require such studies when scientifically warranted, and require the agency to notify sponsors early if additional studies would be needed. Schrier, a pediatrician who lives with type 1 diabetes, framed the bill around insulin costs, saying she had "seen firsthand how skyrocketing insulin prices have threatened access" to lifesaving medication.

Five days later, the House Committee on Energy and Commerce folded HR 9661 into a 29-bill markup, reporting it unanimously along with the Biosimilar Red Tape Elimination Act (HR 5526).

 On July 22, the Senate Committee on Health, Education, Labor, and Pensions (HELP) approved the Senate companion, S 1414, by a vote of 22-0 as amended.

"Comparative efficacy studies are rarely necessary to demonstrate biosimilarity," said Alex Keeton, executive director of the Biosimilars Council, after the Senate vote.

Senator Ashley Moody (R, Florida) introduced the newest measure, S 5059, on July 21, a bill to amend the Public Health Service Act to streamline the review of biosimilar biological products.

 It drew 3 cosponsors and was referred to the HELP committee, where it has seen no further action.

The Biosimilar Red Tape Elimination Act has been reintroduced across 3 consecutive Congresses. Senator Mike Lee (R, Utah) introduced the current Senate version, S 1954, in June 2025, with Senators Ben Ray Luján (D, New Mexico), Rand Paul (R, Kentucky), and Maggie Hassan (D, New Hampshire). It would deem FDA-licensed biosimilars interchangeable with their reference products, eliminating the switching studies the US uniquely requires. The bill cleared the HELP committee in June 2026.

 The House version, introduced by Representative August Pfluger (R, Texas) and Representative Greg Landsman (D, Ohio) in September 2025, sat in Energy and Commerce for 10 months before this week's markup.

"Legacy regulations can often outlive their usefulness," said John Murphy III, president and CEO of the Association for Accessible Medicines.

The STOP GAMES Act (HR 8908), introduced in May 2026 by Representative Eric Sorensen (D, Illinois) and Representative Stephanie Bice (R, Oklahoma), would direct the FDA to weigh specific factors for spotting delay-tactic citizen petitions and refer them to the Federal Trade Commission.

 Earlier versions stalled in 3 Congresses. It appeared on the July markup agenda, though committee records still listed it as referred.

The Biosimilar Inspection Modernization Act (S 3510), introduced in December 2025 by Senators Ted Budd (R, North Carolina) and Hassan, would expand remote regulatory assessments, convene a public meeting on mutual recognition agreements, and require an FDA strategic plan on domestic inspections.

 Julie Reed, executive director of the Biosimilars Forum, said the bill would bring biosimilar reviews "consistency with other drug classes under FDA review."

Regulatory reform covers only part of the pipeline. Testifying before the House Committee on Ways and Means Subcommittee on Health in April 2025, Aaron S. Kesselheim, MD, JD, MPH, urged lawmakers to advance laws "making it harder for manufacturers to build large thickets of biologic patents," restricting pharmacy benefit manager rebate practices that favor higher-cost originators, and changing CMS rules to permit common billing codes for biologics and biosimilars.

Craig Burton, then executive director of the Biosimilars Council, told the same panel that inaction carried consequences, calling it "a crisis that will impact real people," and pointed to the roughly 860,000 Medicare beneficiaries with diabetes who could benefit. The HELP committee advanced the INSULIN Act of 2026 by 17-5 that same day, though no pending bill directly ties insulin affordability to biosimilar competition.

Reimbursement design remains unaddressed. Sonia T. Oskouei, PharmD, vice president of biosimilars and specialty at Sandoz, argues that the average sales price model and Medicare Part B incentives undercut long-term investment while maintaining that "the biosimilar void is not permanent."

 A Matrix Global Advisors analysis found that price negotiation under the Inflation Reduction Act may deter biosimilar entry for high-revenue biologics, estimating that delayed competition for one biologic with $3.5 billion in annual sales could forfeit $1.9 billion yearly.

A Samsung Bioepis white paper has termed this gap the "biosimilar void," noting that only 12 of the 118 biologics projected to lose patent exclusivity between 2025 and 2034 currently have biosimilars in development.

 With several of these measures now moving through both chambers at once, Congress has an opening to close that gap and let biosimilars deliver the savings and access patients have been waiting for.

Congressmembers Langworthy and Schrier introduce a bipartisan bill to lower prescription drug costs by expanding access to biosimilars. News release. Office of Representative Nick Langworthy; July 15, 2026. Accessed July 23, 2026. 

https://langworthy.house.gov/media/press-releases/expedited-access-to-biosimilars-act

Chairman Guthrie announces full committee markup of 29 bills. News release. House Committee on Energy and Commerce; July 2026. Accessed July 23, 2026. 

https://energycommerce.house.gov/news/markups

AAM and the Biosimilars Council praise House action on biosimilar bills. 

. July 22, 2026. Accessed July 23, 2026. 

https://chaindrugreview.com/aam-biosimilars-council-praise-house-action-on-biosimilar-bills/

Chairman Cassidy advances legislation improving families' access to quality, affordable health care. News release. US Senate Committee on Health, Education, Labor and Pensions; July 22, 2026. Accessed July 23, 2026. 

https://www.help.senate.gov/rep/newsroom/press/chairman-cassidy-advances-legislation-improving-families-access-to-quality-affordable-health-care

The Biosimilars Council and AAM applaud the Senate markup and committee passage of the Expedited Access to Biosimilars Act. 

. July 23, 2026. Accessed July 23, 2026. 

https://chaindrugreview.com/the-biosimilars-council-and-aam-applaud-senate-markup-and-committee-passage-of-the-expedited-access-to-biosimilars-act/

A bill to amend the Public Health Service Act to streamline the review of biosimilar biological products, S 5059, 119th Cong (2026). Accessed July 23, 2026. 

https://www.congress.gov/bill/119th-congress/senate-bill/5059

AAM applauds momentum as two bills move through the Senate HELP Committee. News release. Association for Accessible Medicines; June 17, 2026. Accessed July 23, 2026. 

https://accessiblemeds.org/resources/press-releases/aam-applauds-momentum-two-bills-move-through-senate-help-committee/

Biosimilar Red Tape Elimination Act, HR 5526, 119th Cong (2025). Accessed July 23, 2026. 

https://www.congress.gov/bill/119th-congress/house-bill/5526

STOP GAMES Act of 2026, HR 8908, 119th Cong (2026). Accessed July 23, 2026. 

https://www.congress.gov/bill/119th-congress/house-bill/8908

Biosimilar Inspection Modernization Act of 2025, S 3510, 119th Cong (2025). Accessed July 23, 2026. 

https://www.congress.gov/bill/119th-congress/senate-bill/3510

Senators Budd and Hassan introduce a bipartisan bill to lower prescription drug prices for American families. News release. Office of Senator Ted Budd; December 17, 2025. Accessed July 23, 2026. 

Jeremias S. Experts pressure Congress to remove roadblocks for biosimilars. The Center for Biosimilars

. April 12, 2025. Accessed July 23, 2026. 

https://www.centerforbiosimilars.com/view/experts-pressure-congress-to-remove-roadblocks-for-biosimilars

Santoro C. Addressing patent abuse, reimbursement models key to sustainable biosimilar market. The Center for Biosimilars. April 25, 2025. Accessed July 23, 2026. 

https://www.centerforbiosimilars.com/view/addressing-patent-abuse-reimbursement-models-key-to-sustainable-biosimilar-market

Jeremias S. Medicare price negotiations will slow biosimilar momentum, widening market gap. The Center for Biosimilars. July 16, 2025. Accessed July 23, 2026. 

https://www.centerforbiosimilars.com/view/medicare-price-negotiations-will-slow-biosimilar-momentum-widening-market-gap

Jeremias S. White paper offers tips for sustaining biosimilar progress, avoiding a market void. The Center for Biosimilars. July 15, 2025. Accessed July 23, 2026. 

https://www.centerforbiosimilars.com/view/white-paper-offers-tips-for-sustaining-biosimilar-progress-avoiding-a-market-void

Congress fast-tracks biosimilar bills to cut drug and insulin costs, while patent, rebate, and reimbursement roadblocks still stall competition.

Biosimilar Bills Gain Steam in Congress, But Key Reforms Still Wait

The FDA accepted for review 2 abbreviated new drug applications (ANDAs) from Sandoz for generic versions of tirzepatide, the company announced on June 29, 2026.¹ The applications sought approval for an in-house Sandoz generic version of the tirzepatide autoinjector, a gastric inhibitory polypeptide receptor and glucagon-like peptide-1 (GLP-1) receptor agonist, and both filings, submitted through the FDA generic pathway, addressed all indications of the reference products, Mounjaro and Zepbound.

glp-1 | Image credit: zimmytws - stock.adobe.com

For Mounjaro, those indications included use as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients 10 years and older with type 2 diabetes. For Zepbound, they included use alongside a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction in adults with obesity or who are overweight and have at least 1 weight-related condition, as well as treatment of moderate to severe obstructive sleep apnea in adults with obesity.

Sandoz described the submission as in-house development that combined its small molecule and device expertise with techniques drawn from its biosimilar work.¹ The company positioned the program within a broader access strategy, noting that type 2 diabetes remained the costliest chronic condition in the US and that obesity rates had tripled since 1960. Subject to approval, the product could be among the first generic tirzepatide options available to patients in the US once market conditions allowed, and the company framed GLP-1 medicines as a long-term opportunity, citing reference medicines with a combined value of more than $650 billion expected to lose patent protection over the next decade. 

Biosimilar Development Gap Shapes Industry Context

Although the tirzepatide filings followed the generic rather than the biosimilar pathway, the announcement arrived as the biosimilar sector continued to confront a widely discussed development gap. Reporting from The Center for Biosimilars

 has described a "biosimilar void," in which most biologics scheduled to lose exclusivity lacked a biosimilar in development.² Of the roughly 118 biologics expected to lose exclusivity over the coming decade, only about 10% had a biosimilar candidate in the pipeline, a shortfall that left therapeutic areas such as neurology, diabetes, and hematology with restricted competition. 

High development cost was identified as a primary driver of that gap.³ Biosimilar development was estimated to range from $100 million to $250 million per product, a figure paired with a low projected return on investment that discouraged work on lower-sales biologics, while additional barriers included regulatory requirements for extensive studies, payer controls, provider preferences, and patent litigation that delayed some launches, as seen in the adalimumab market.

Stakeholders have estimated that the gap could translate into $232 billion in unrealized savings over 10 years if development and adoption trends did not accelerate.⁴ Regulatory changes could alter that calculation, as draft FDA guidance proposing to eliminate comparative efficacy studies for most biosimilar applications was estimated to save manufacturers up to $100 million in development costs per product and to shorten development timelines by as much as half.

Sandoz described itself as a global leader in generic and biosimilar medicines.¹ The company markets one of the larger biosimilar portfolios in the US, anchored by Zarxio (filgrastim-sndz), which became the first biosimilar approved in the country in 2015.² Its more recent biosimilars have included Hyrimoz (adalimumab-adaz), Pyzchiva (ustekinumab-ttwe), Tyruko (natalizumab-sztn), and the denosumab biosimilars Wyost and Jubbonti, which launched in 2025 as the first denosumab biosimilars in the US.⁵ The portfolio spans immunology, oncology supportive care, ophthalmology, and bone health.

The FDA had not confirmed a review timeline, and, subject to approval, the generic could reach patients only after exclusivity and patent barriers were resolved.¹

US FDA accepts Sandoz applications for proposed in-house development of generic tirzepatide GLP-1s. News release. Sandoz; June 29, 2026. Accessed July 13, 2026. 

https://www.sandoz.com/us-fda-accepts-sandoz-applications-proposed-house-development-generic-tirzepatide-glp-1s

Jeremias S. The biosimilar void: 90% of biologics coming off patent will lack biosimilars. The Center for Biosimilars

. February 5, 2025. Accessed July 13, 2026. 

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

Jeremias S. Top 5 most-read biosimilar news of 2025. The Center for Biosimilars. December 17, 2025. Accessed July 13, 2026. 

https://www.centerforbiosimilars.com/view/top-5-most-read-biosimilar-news-of-2025

Jeremias S. Cardinal Health biosimilar report: $56 billion in savings and the road to market sustainability. The Center for Biosimilars. February 24, 2026. Accessed July 13, 2026. 

https://www.centerforbiosimilars.com/view/cardinal-health-biosimilar-report-56-billion-in-savings-and-the-road-to-market-sustainability

Jeremias S. Sandoz, STADA, and Samsung Bioepis report strong earnings from biosimilars. The Center for Biosimilars. June 10, 2025. Accessed July 13, 2026. 

https://www.centerforbiosimilars.com/view/sandoz-stada-and-samsung-bioepis-report-strong-earnings-from-biosimilars

Sandoz moves toward US generic tirzepatide autoinjectors as FDA reviews ANDAs, signaling future GLP‑1 access amid patent and biosimilar gaps.

FDA Accepts Sandoz Generic Tirzepatide Applications Amid Biosimilar Development Gap

More than half of India's health care spending is paid directly out-of-pocket, and for people who need repeated intravitreal injections to preserve their sight, that arithmetic often determines whether treatment continues or lapses. A narrative review published in the 

 examined how biosimilar anti–vascular endothelial growth factor (anti-VEGF) agents have reshaped that calculation, concluding that these lower-cost molecules delivered clinical outcomes closely mirroring the reference biologic across major retinal vascular diseases.

Biosimilar anti-VEGF agents matched reference ranibizumab in vision outcomes and safety across retinal diseases in India, at substantially lower cost. | Image credit: Syda Productions - stock.adobe.com

Affordability Barriers Driving the Need for Accessible Therapy

Retinal vascular diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO), represented a major and growing cause of visual morbidity in India. Diabetes was projected to affect nearly 100 million people in the country by 2045, driving a rise in DME, while population aging elevated the burden of nAMD. 

Anti-VEGF therapy transformed management of these conditions, but sustained benefit depended on timely initiation and repeated dosing. The cumulative cost of monthly, pro-re-nata, or treat-and-extend regimens imposed a substantial financial burden, and affordability-related undertreatment was common, with patients in India often receiving far fewer injections than those administered in randomized trials.

India held a pioneering position in this landscape, having become the first country to approve and commercialize an intravitreal ranibizumab biosimilar, Razumab, in 2015, ahead of approvals in Europe and the US. The Drug Controller General of India subsequently approved additional ranibizumab biosimilars, alongside a recently launched aflibercept biosimilar.

India's regulatory environment for these products has continued to evolve alongside its expanding market. The Central Drugs Standard Control Organisation issued a 2025 draft guideline on similar biologics that a Center for Biosimilars analysis described as a meaningful step toward harmonizing Indian requirements with standards set by the European Medicines Agency, the FDA, and the UK's Medicines and Healthcare products Regulatory Agency.

 The draft de-emphasized in vivo animal testing in favor of in vitro comparability assays, permitted waivers of confirmatory phase 3 efficacy trials under defined conditions of high analytical and pharmacokinetic comparability, and adopted a risk-based approach to immunogenicity assessment. The analysis noted that further refinement of statistical criteria and extrapolation rationale would strengthen global acceptability, positioning the framework as a potential model for other emerging markets modernizing their biosimilar pathways.

Phase 3 and Real-World Data Confirmed Therapeutic Equivalence

Across major indications, phase 3 trials consistently demonstrated equivalence or noninferiority to the reference molecule in visual and anatomical outcomes, with comparable safety and low immunogenicity.

 In nAMD, visual gains improvements with ranibizumab biosimilars generally ranged between 6 and 8 Early Treatment Diabetic Retinopathy Study letters, accompanied by 120 to 170 µm reductions in central retinal thickness within the first 3 to 6 months. In DME, mean visual acuity gains of approximately 8 letters were reported, with reductions in central retinal thickness that fell within prespecified equivalence margins. For RVO, real-world cohorts showed meaningful gains in best-corrected visual acuity and significant reductions in intraretinal and subretinal fluid over follow-up extending to 48 weeks.

Large real-world datasets corroborated these findings. The CRIBS study (2024), a multicenter retrospective safety analysis, evaluated 39,226 eyes across 46,520 injections in patients with nAMD, DME, RVO, and myopic choroidal neovascularization, reporting that severe events were extremely rare. The Razumab Safety Study (2021) prospectively followed 6404 eyes across 9140 injections in patients with mixed retinal diseases, documenting very low major adverse event rates. Anti-drug antibody positivity remained low and balanced across groups, and post-marketing studies showed no unexpected inflammation patterns.

Economic Modeling Reinforced the Case for Biosimilar Adoption

A Markov model simulating lifetime outcomes for a cohort of people with nAMD in Japan found that a ranibizumab biosimilar was cost-saving relative to branded ranibizumab and aflibercept across typical nAMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation subtypes, with incremental lifetime costs favoring the biosimilar from both societal and patient perspectives.

 Such modeling supported the review's contention that lower acquisition costs allowed earlier initiation and more frequent retreatment.

The review noted several constraints. Evidence for myopic choroidal neovascularization remained limited, and data specific to polypoidal choroidal vasculopathy were sparse and largely indirect. Non-nAMD indications were dominated by observational designs, long-term treat-and-extend data were limited, and outcomes in retinopathy of prematurity remained underrepresented. Bevacizumab biosimilars, approved in India for oncology rather than ophthalmology, lacked intravitreal phase 3 data, and their ophthalmic use remained off-label.

The authors framed the significance of their synthesis directly, writing that "the affordability of biosimilar anti-VEGF enhances its potential as an alternative, particularly in resource-limited settings, without compromising safety." They called for long-term durability analyses, disease-specific subgroup studies, and prospective cost-effectiveness modeling tailored to the Indian healthcare system.

Chakraborty D, Sinha TK, Boral S, Das A. Biosimilar anti-vascular endothelial growth factor agents: clinical outcomes, safety, and cost-effectiveness in India. 

 2026;74(5):760-766. doi:10.4103/IJO.IJO_3222_25

Yanagi Y, Takahashi K, Iida T, et al. Cost-effectiveness analysis of ranibizumab biosimilar for neovascular age-related macular degeneration and its subtypes from the societal and patient perspectives in Japan. 

 2024;13(7):2005-2021. doi:10.1007/s40123-024-01011-z. Accessed July 9, 2026. 

https://link.springer.com/article/10.1007/s40123-024-01011-z

BioRationality: the revised Indian biosimilar guidelines finally bring rationality. Center for Biosimilars. May 19, 2025. Accessed July 9, 2026. 

https://www.centerforbiosimilars.com/view/biorationality-the-revised-indian-biosimilar-guidelines-finally-bring-rationality

Biosimilar anti-VEGF agents matched the reference ranibizumab in vision outcomes and safety across retinal diseases in India, at a lower cost.

Anti-VEGF Biosimilars Match Reference Drug in Indian Retinal Disease Care

A lower-cost biosimilar of rituximab produced remission rates on par with the reference product in adults with membranous nephropathy, offering early real-world support for a treatment that carries a substantial price advantage.

Real-world data shows rituximab biosimilars for membranous nephropathy match remission rates, cut costs, and expand treatment options. | Image credit: dream@do - stock.adobe.com

The retrospective analysis, conducted at a single tertiary center in Beijing, reviewed the records of 201 adults with membranous nephropathy (MN) who received high-dose rituximab biosimilar HLX01 and were followed for at least 1 year between January 2020 and December 2022.

 Rituximab, a monoclonal antibody that depletes CD20-positive B cells, is recommended as a first-line option for moderate- and high-risk MN in the 2021 Kidney Disease: Improving Global Outcomes guidelines, although the indication remains off-label. HLX01 became the first rituximab biosimilar approved in China, in 2019.

Biosimilar Data in Membranous Nephropathy Remained Scarce

Prior clinical trials had established that rituximab biosimilars matched the originator on pharmacokinetics, B-cell depletion, and safety in lymphoma and rheumatoid arthritis, but data on high-dose rituximab for MN were limited, and evidence for biosimilars in the indication was scarcer still. The analysis was designed to address that gap by measuring efficacy and tolerability in routine practice.

Over the 1-year follow-up, 151 of 201 patients achieved remission, an overall rate of 75.12%, with 53 reaching complete remission and 98 reaching partial remission. The median time to remission was 6 months. Patients who were treatment-naive achieved remission at 78.79%, and those previously treated at 73.33%, a difference that did not reach statistical significance (

 = .40). Among patients who achieved remission, 12 (7.95%) relapsed, and 7 of those regained remission after readministration.

Laboratory measures reinforced the response. Serum albumin rose from a baseline mean of 28.4 g/L to 38.6 g/L at 12 months, and proteinuria fell from a median of 4.27 g/24 h to 0.96 g/24 h, with both changes statistically significant (

 < .001). Serum creatinine remained stable, indicating preserved kidney function. The remission rate fell within the range reported for innovator rituximab in earlier MN trials, including the 60% 12-month rate in the MENTOR trial (NCT01180036) and the 58% 24-month rate in the STARMEN trial (NCT01955187).

Anti-phospholipase A2 receptor antibody (PLA2Rab) status at baseline was associated with outcomes. Patients who were PLA2Rab-negative at baseline reached a 12-month remission rate of 86.67%, compared with 72.26% among those who were positive (

 = .03), although the negative group also entered treatment with significantly lower baseline proteinuria. The overall antibody negative conversion rate was 77.37% among baseline-positive patients.

Patient demographics reflected a profile typical of the disease, comprising 111 men and 90 women, a mean age of 53 years, and a mean body mass index of 25.8 kg/m

. About 40% received the biosimilar alone, and the remainder received it alongside at least one immunosuppressant. Adverse events occurred in 62 of 201 patients, an incidence of 30.85%, with flushing accompanied by pruritus or rash reported most often. Most reactions were transient and eased after temporary infusion suspension and intramuscular diphenhydramine. Serious adverse reactions were recorded in 2 patients (1.00%), both prompting discontinuation. All observed reactions were previously documented effects of rituximab.

Cost Savings Anchored the Biosimilar Rationale

Affordability underpinned the rationale for the biosimilar. In this cohort, the 201 patients received a combined 374 g of the product, priced at 60.9% of the innovator, translating to average savings of roughly ¥11,436.8 per patient per year. That direction mirrors trends in the US, where uptake of rituximab biosimilars rose from between 0% and 7% of claims in 2019 to a majority of Medicare Part B and Medicaid rituximab claims by 2022, a shift accompanied by declining per-unit costs across programs.

The authors concluded that the efficacy and safety of the high-dose rituximab biosimilar in MN were "consistent with those of innovator products and that it can be used as a first-line treatment option for membranous nephropathy."

The authors flagged several constraints. As a single-center retrospective study, the analysis carried risks of incomplete data, particularly on safety, and the one-year follow-up restricted assessment of long-term efficacy and tolerability. They called for prospective, multicenter, randomized trials and the determination of individualized pharmacokinetic and pharmacodynamic parameters to confirm the results.

Zou Y-Z, Du X-L, Wang S-H, Dai R, Xiao R, Wang B. A retrospective study of the efficacy and safety of rituximab biosimilar for the treatment of membranous nephropathy. 

 Published online May 29, 2026. doi:10.1186/s40360-026-01155-7

Qian J. Uptake of rituximab biosimilars in Medicare and Medicaid in 2019-2022. 

 2024;30(12):e359-e363. doi:10.37765/ajmc.2024.89644

Real-world data shows rituximab biosimilars for membranous nephropathy match remission rates, cut costs, and expand treatment options.

Rituximab Biosimilar Reached 75% Remission, Matched Innovator in Membranous Nephropathy

Patients with moderate to severe plaque psoriasis who alternate between a reference biologic and its biosimilar counterpart don't have to worry that the change in manufacturer will compromise their treatment outcomes, according to new trial data supporting interchangeability between ABP 654 and the ustekinumab reference product.

Trial data show switching between ABP 654 and reference ustekinumab maintains similar psoriasis control, safety, and immunogenicity, supporting FDA interchangeability confidence. | Image Credit: pimentos - stock.adobe.com

The randomized, double-blinded study evaluated pharmacokinetics (PK), efficacy, immunogenicity, and safety following 3 switches between ABP 654 (ustekinumab-auub; marketed as Wezlana/Wezenla) and the ustekinumab reference product (Stelara) in adults with moderate to severe plaque psoriasis. The findings, 

, contributed to the FDA's October 2023 approval of ABP 654 as the first interchangeable biosimilar to ustekinumab available in the US.

Why Interchangeability Data Matter for Biosimilar Adoption

Although biosimilars share the same amino acid sequence, structure, mechanism of action, and clinical performance as their reference products, US pharmacists cannot substitute a biosimilar for its reference product without prescriber consultation unless the FDA has designated it interchangeable. That designation requires demonstrating that switching between the 2 products carries no greater risk to safety or efficacy than remaining on the reference product alone, a bar intended to ease provider and patient concerns about switching therapies.

Real-world evidence has echoed these controlled-trial findings across other dermatologic biologics. A systematic review of real-world switching studies among patients with psoriasis, psoriatic arthritis, and hidradenitis suppurativa who transitioned between originator and biosimilar versions of adalimumab, etanercept, and infliximab found that switching was generally safe and effective, though a subset of patients experienced treatment discontinuation linked to perceived loss of efficacy or adverse events rather than objective disease measures.

The review's authors pointed to the nocebo effect, in which negative patient expectations rather than pharmacologic differences may drive perceived treatment failure, as a possible explanation for these outcomes, underscoring the importance of patient and provider education alongside robust interchangeability data like that generated in the ABP 654 trial.

Trial Design Included Run-In and Switching Periods

The trial (NCT04761627) enrolled 494 patients across 87 centers in 8 countries.

 During a run-in period, participants received the reference product at day 1, week 4, and week 16. Of these, 453 patients achieved at least a 50% improvement in Psoriasis Area and Severity Index (PASI) score and were randomized in a 1:1 ratio to a Continued-Use group (n = 225), which stayed on the reference product at weeks 28, 40, and 52, or a Switching group (n = 228), which received ABP 654 at week 28, the reference product at week 40, and ABP 654 again at week 52. Baseline characteristics were comparable between groups, with a mean age of approximately 47 to 48 years, mean baseline PASI scores near 20, and roughly 40% of patients in each group having prior biologic exposure for psoriasis.

The study's primary endpoints, area under the concentration-time curve and maximum concentration between weeks 52 and 64, produced geometric mean ratios of 0.93 and 0.95, respectively, both falling within the prespecified similarity margin of 0.8 to 1.25. Secondary PK measures, including trough concentrations at steady state, also remained within this range at each assessed time point.

Trial data show switching between ABP 654 and reference ustekinumab maintains similar psoriasis control, safety, and immunogenicity, supporting FDA interchangeability confidence.

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