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

Skylar Jeremias

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

Articles

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.

Efficacy and Safety Outcomes Were Comparable

At week 64, patients in the switching and continued-use arms showed similar PASI percent improvement from baseline (88.8% vs 88.7%, respectively), along with comparable rates of PASI 75 response (83.3% vs 82.8%) and PASI 100 response (36.1% vs 35.8%). Rates of antidrug antibodies were likewise comparable between groups, and adverse events occurred at similar frequencies, largely of mild to moderate severity, with grade 3 or higher events reported in 2.8% of patients in each arm.

The authors noted the trial results indicate "any reduced efficacy or safety resulting from switching between ABP 654 and ustekinumab [reference product] is not greater than the risk of ustekinumab [reference product] treatment without switching."

Limitations Center on Responder Population

Because only patients who achieved at least a PASI 50 response during the run-in period advanced to randomization, the efficacy, safety, and immunogenicity findings apply specifically to treatment responders and may not extend to primary non-responders or those with evolving disease. The authors emphasized, however, that the trial was powered specifically to detect PK similarity, an outcome not expected to be meaningfully influenced by responder status.

The results arrive as FDA guidance has evolved: as of June 2024, the agency indicated that dedicated switching studies are generally no longer required to support interchangeability designations, with manufacturers instead able to rely on scientific justification from existing biosimilarity data.

Blauvelt A, Bagel J, Pinter A, et al. Repeated switching between biosimilar ABP 654 and reference ustekinumab in patients with moderate-to-severe plaque psoriasis: a randomized, double-blinded clinical trial to support interchangeability. 

. Published online May 29, 2026. doi:10.1093/bjd/ljag218

Nicoletti MM, Crisci E, Pentella C, Cantone A, Ruggiero D, Anatriello A, Scavone C. Switching between originators and biosimilars in dermatology: a systematic review of real-world clinical studies. 

. 2023;3(2):95-115. doi:10.3390/biologics3020006

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

Biosimilar ABP 654 Maintains Efficacy, Safety After Repeated Switching From Ustekinumab

For postmenopausal women managing osteoporosis, the high cost of biologic therapies like denosumab has long stood between patients and consistent access to fracture prevention. A new phase 3 trial suggests a lower-cost alternative may close that gap without compromising results.

Phase 3 data show denosumab biosimilar KN012 matches Prolia on bone density and safety, promising cheaper fracture protection. | Image credit: SoftSheep - stock.adobe.com

Trial Compares Biosimilar to Reference Denosumab

Researchers evaluated KN012, a proposed biosimilar to denosumab, against the US reference product (Prolia) in a 12-month, double-blind, randomized, active-controlled phase 3 study conducted across 25 centers in China (CTR20201555). Denosumab, a fully human monoclonal antibody targeting RANKL, inhibits RANK–RANKL signaling, reduces osteoclast activity and bone resorption, and thereby increases bone mass and strength. While the reference drug has demonstrated years of proven efficacy and safety, treatment costs have remained a barrier to access.

That access gap has persisted despite the drug's long track record. A recent review noted that osteoporosis remains marked by delayed diagnosis, undertreatment, and poor adherence even though effective therapies exist, and pointed to denosumab biosimilars as a means of narrowing that gap.

 Since 2024, several denosumab biosimilars have secured approval from regulators, including the FDA and European Medicines Agency, reflecting a broader international push to widen access to antiresorptive therapy for patients at risk of fracture. The Chinese trial adds to that growing body of comparative evidence supporting biosimilar adoption in osteoporosis care.

Investigators enrolled 280 postmenopausal women between the ages of 50 and 80 years who were at high risk of fracture, randomizing them 1:1 to receive 60 mg of either KN012 or the reference drug subcutaneously at baseline and month 6. All patients also received daily calcium and vitamin D supplementation throughout the study. Of those randomized, 279 patients received treatment, and 262 (93.6%) completed the study period.

Bone Density Gains Were Comparable Between Groups

The primary endpoint, mean percent change in lumbar spine bone mineral density (BMD) from baseline at month 12, showed a least squares mean difference of 0.22% between the biosimilar and reference groups in the full analysis set, and 0.11% in the per-protocol set. Both confidence intervals fell entirely within the prespecified equivalence margin of plus or minus 1.75%, meeting the trial's equivalence criteria. Lumbar spine BMD increased by roughly 5.8% in the biosimilar group and 5.5% in the reference group by month 12, figures the authors noted were consistent with earlier pivotal trial data for the reference drug. Similar gains were observed at the total hip, femoral neck, and trochanter, with no statistically significant differences between treatment arms. Bone turnover markers, including serum CTX and PINP, declined by at least 60% from baseline across both groups, reflecting expected suppression of bone resorption and formation activity.

Safety and Immune Response Profiles Aligned Closely

Treatment-emergent adverse events occurred in similar proportions between groups, affecting 85.7% of patients receiving the biosimilar and 86.3% of those receiving the reference drug. Adverse drug reactions occurring in more than 5% of patients in either group included hypocalcemia, hypophosphatemia, and urinary tract infection, with comparable rates across arms. Serious adverse events were reported in 8.6% of the biosimilar group and 13.7% of the reference group. Immunogenicity testing showed low rates of antidrug antibodies in both groups, and no patients in either arm tested positive for neutralizing antibodies at any point during the study.

Population pharmacokinetic modeling, conducted using data from 277 patients, further supported the comparison. Geometric mean ratios for key pharmacokinetic parameters and their 90% confidence intervals fell entirely within the standard bioequivalence range of 80% to 125%.

Findings Build on Limited Head-to-Head Comparisons

The authors noted that this trial represented the first active-controlled, head-to-head phase 3 comparison between a denosumab biosimilar and the reference product in a Chinese population, distinguishing it from prior placebo-controlled biosimilar studies conducted in the same country. As they explained, this design "addresses the inferential limitations of placebo controls for equivalence testing and provides more direct, robust evidence of clinical equivalence."

Still, the trial carried limitations common to biosimilar development programs. The 12-month observation window was considerably shorter than the multiyear safety data available for the reference product, limiting insight into rarer, longer-term risks such as atypical femoral fractures or osteonecrosis of the jaw, none of which were observed during this study. The population studied was also limited to Chinese postmenopausal women, and additional research may be needed to confirm generalizability across broader patient populations.

Overall, the authors concluded that the biosimilar demonstrated comparable efficacy, safety, and pharmacokinetic behavior to the reference drug, supporting its potential as an accessible treatment option for postmenopausal women at high risk of fracture.

Zhu X, Liu J, Mao Y, Li J, Shao F, Lin H. Comparison of KN012, a denosumab biosimilar, versus reference denosumab in Chinese postmenopausal women with osteoporosis: efficacy, safety, and population pharmacokinetics in a 12-month phase III study. 

. 2026;29:101916. doi:10.1016/j.bonr.2026.101916

Aapro M, Hadji P, Santini D, Schmidmaier R, Eastell R. Biosimilars in osteoporosis treatment: focus on denosumab. 

. 2025;25(8):887-898. doi:10.1080/14712598.2025.2540471

Phase 3 data show denosumab biosimilar KN012 matches Prolia for BMD gains and safety, potentially expanding affordable osteoporosis care.

Biosimilar Denosumab Matches Reference Drug for Bone Density in Chinese Women

Biosimilar developers across the globe advanced their pipelines and portfolios in recent weeks, with new FDA indication expansions, a European product launch, and a fresh regulatory acceptance, signaling continued momentum toward expanded patient access to biologic medicines.

FDA expands Tofidence uses, Teva launches Eylea biosimilar in Europe, and Alvotech nears Entyvio rival—accelerating biosimilar access and savings. | Image credit: Mongkolchon - stock.adobe.com

Organon announced that the FDA approved a supplemental Biologics License Application (sBLA) for Tofidence (tocilizumab-bavi), a biosimilar referencing Actemra (tocilizumab), expanding the product's approved indications to include 2 serious conditions. The newly approved indications cover treatment of adults and pediatric patients 2 years of age and older with chimeric antigen receptor (CAR) T cell–induced severe or life-threatening cytokine release syndrome (CRS), as well as hospitalized adult and pediatric patients aged 2 years and older with coronavirus disease 2019 (COVID-19) who are receiving systemic corticosteroids and require supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Tofidence, the first approved tocilizumab biosimilar entrant in the US market, launched in May 2024 and was already indicated for moderately to severely active rheumatoid arthritis (RA), giant cell arteritis (GCA), polyarticular juvenile idiopathic arthritis (PJIA), and systemic juvenile idiopathic arthritis (SJIA). Organon acquired the regulatory and commercial rights to Tofidence in the US in 2025. The expanded label positions the product as a lower-cost alternative to the reference biologic in critical care and oncology support settings, where biosimilar adoption could meaningfully reduce costs for health systems managing high-acuity patients.

Teva Brings Aflibercept Biosimilar to European Markets

Teva Pharmaceutical Industries announced the European launch of Ahzantive (aflibercept), a biosimilar to Eylea (aflibercept), marking the company's entry into the ophthalmology biosimilar space. The launch of Ahzantive prefilled syringes began in May 2026 across several European markets, including France, Germany, Spain, and the Netherlands, with Teva expecting to launch in additional markets later in the year.

Ahzantive received European Commission approval in 2025 for treatment of neovascular age-related macular degeneration and other serious retinal diseases, including diabetic macular edema, visual impairment due to myopic choroidal neovascularization, and macular edema following retinal vein occlusion. The launch followed Teva's semi-exclusive commercialization agreement with Klinge Biopharma GmbH and Formycon AG in major parts of Europe and Israel. Teva reported it has one of the world's largest biosimilar portfolios globally, with 11 biosimilars on the market and 13 products in its pipeline across therapeutic areas, including oncology, immunology, ophthalmology, and respiratory care. The European ophthalmology biosimilar space is considered a significant opportunity for cost savings given the widespread chronic use of anti-vascular endothelial growth factor agents for retinal disease management.

FDA Accepts Alvotech's Entyvio Biosimilar Application

Rounding out a busy stretch for the biosimilar sector, Alvotech announced that the FDA accepted for review a BLA for AVT16, a proposed interchangeable biosimilar to Entyvio (vedolizumab) for intravenous administration in adults with inflammatory bowel disease. The BLA submission is supported by a comprehensive data package, including analytical, pharmacokinetic, and immunogenicity data generated to demonstrate biosimilarity between AVT16 and the reference product.

If the FDA approves AVT16 with an interchangeable designation, it could be substituted for Entyvio at pharmacies without prescriber intervention, a status that carries significant commercial advantages in the US market. Under a partnership with Teva, Alvotech is responsible for development and manufacturing of AVT16, while Teva is responsible for commercialization. Alvotech shares jumped approximately 12% in premarket trading following the announcement. Separately, in February 2026, Alvotech announced positive results from a pivotal pharmacokinetic study for AVT80, a proposed biosimilar to Entyvio for subcutaneous administration, suggesting the company is pursuing multiple pathways to compete in the vedolizumab market.

Organon secures US Food and Drug Administration approval expanding indications for Tofidence (tocilizumab-bavi) in cytokine release syndrome (CRS) and pediatric COVID-19. Press release. Organon; June 10, 2026. 

https://www.businesswire.com/news/home/20260610519993/en/Organon-Secures-US-Food-and-Drug-Administration-Approval-Expanding-Indications-for-TOFIDENCE-tocilizumab-bavi-in-Cytokine-Release-Syndrome-CRS-and-Pediatric-COVID-19

Teva expands European biosimilars portfolio with launch of Ahzantive (aflibercept) biosimilar to Eylea. Press release. Teva Pharmaceutical Industries Ltd; June 4, 2026. 

https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2026/Teva-Expands-European-biosimilars-portfolio-with-launch-ofAHZANTIVEaflibercept-biosimilar-to-Eylea/default.aspx

Alvotech announces FDA acceptance of biologics license application for AVT16, a proposed interchangeable biosimilar to Entyvio. Press release. Alvotech; June 8, 2026. 

https://www.globenewswire.com/news-release/2026/06/08/3307832/0/en/alvotech-announces-fda-acceptance-of-biologics-license-application-for-avt16-a-proposed-interchangeable-biosimilar-to-entyvio.html

FDA expands Tofidence uses, Teva launches Eylea biosimilar in Europe, and Alvotech’s Entyvio rival enters FDA review—boosting access.

Biosimilar Makers Push Forward on Regulatory and Commercial Fronts

Patients with moderate to severe Crohn disease in Spain could experience improved outcomes and lower treatment costs when biosimilar ustekinumab is used as a first-line therapy rather than reserved for later lines, according to a cost-effectiveness analysis 

Early use of ustekinumab biosimilars in Spain shows cost-effective Crohn disease care, boosting QALYs and cutting NHS spend—insights for Europe. |Image credit: mi_viri - stock.adobe.com

Crohn disease imposes a considerable economic burden on national health systems, with annual costs per patient in Spain reported to range from €11,000 to €18,000—differences driven largely by pharmacological expenses rather than other direct health care costs.

 offered important context for why this economic question matters at the bedside.

 Reviewers noted that despite ustekinumab's established efficacy in moderate to severe Crohn disease, its high acquisition cost had historically confined it to later lines of therapy, typically after patients experienced treatment failure on 1 or more antitumor necrosis factor agents. The availability of biosimilar versions, the review argued, carries the potential to shift that calculus—reducing financial barriers and enabling earlier use in the treatment algorithm, where evidence increasingly supports more aggressive initial intervention. Biosimilar ustekinumab candidates have demonstrated comparable efficacy, safety, pharmacokinetics, and immunogenicity to the reference product in studies conducted to date, though the review noted that real-world data specific to Crohn disease remain limited.

As biologic therapies have become the cornerstone of moderate to severe disease management, appropriate sequencing has grown more consequential both clinically and financially.

 The 2024 ECCO guidelines positioned ustekinumab as a first-line induction and maintenance option for moderate to severe Crohn disease, but until recently, the high acquisition cost of reference ustekinumab limited its appeal as an early-line choice in Spain. The entry of biosimilar ustekinumab (bsUST) into the Spanish market in mid-2024, at an assumed 30% price reduction vs the reference product, prompted investigators to formally evaluate whether repositioning bsUST to the front of treatment sequences would be cost-effective from the perspective of Spain's National Healthcare System (NHS).

Markov Model Evaluated Seven Biosimilar-Inclusive Treatment Sequences

Investigators developed a Markov model with 2-week cycles and a lifetime horizon to compare 7 treatment sequences in adults with moderate to severe Crohn disease. Health states included active disease, response, remission, surgery, and death. Funnel states simulated induction periods, and patients who lost response transitioned to the next treatment line after a 3-month delay to reflect real-world clinical practice. Surgery was considered only after 4 pharmacological lines had been exhausted.

The sequences incorporated biosimilar adalimumab (bsADA), biosimilar intravenous infliximab (bsIFX), bsUST, risankizumab, upadacitinib, and vedolizumab. Sequence 1—bsADA followed by bsUST, upadacitinib, risankizumab, and surgery—served as the reference comparator because it carried the lowest total lifetime cost at €157,224 per patient.

Patient characteristics were drawn from the UNITI-2 trial (NCT01369329) population and validated against Spanish real-world data from the ENEIDA registry. The modeled cohort had a mean age of 39.2 years, was 46.7% women, and had a mean weight of 73.4 kg. Clinical efficacy data were sourced from a published network meta-analysis, with maintenance efficacy for biologic-experienced patients drawn from pivotal trials. A willingness-to-pay (WTP) threshold of €27,000 per quality-adjusted life year (QALY), a benchmark commonly referenced in Spain, was used to assess cost-effectiveness.

Only One Sequence Met Spain's Cost-Effectiveness Threshold

Of the 7 sequences evaluated, only sequence 2—which placed bsUST first, followed by bsADA, upadacitinib, risankizumab, and surgery—met the €27,000/QALY threshold. That sequence yielded an incremental cost-effectiveness ratio (ICER) of €8,672.6/QALY compared with the reference, representing a gain of 0.36 QALYs at an incremental cost of €3080 per patient. All other sequences exceeded the threshold, with ICERs ranging from €42,594/QALY to €372,446/QALY.

Within the base case, the first treatment line in sequence 2 had a mean duration of 3.9 years, compared with 2.2 to 3.3 years in the remaining sequences. Time to surgery ranged from 7.9 years in sequences 2 and 4 to 9 years in sequences 6 and 7.

Probabilistic sensitivity analysis, based on 10,000 Monte Carlo simulations, confirmed the robustness of these findings: sequence 2 was identified as cost-effective in 98.03% of simulations at the €27,000/QALY threshold. Deterministic sensitivity analysis indicated that the ICER was most sensitive to patient weight, first-line pharmacological costs, and the probability of achieving remission during maintenance.

In an alternative reference-analysis setting with sequence 2 as the comparator, all remaining sequences were either dominated or associated with QALY losses, thereby reinforcing the economic case for early bsUST placement.

Cost Savings Driven by Efficacy and Lower Acquisition Costs

The investigators attributed sequence 2's favorable profile to a combination of bsUST's clinical durability and its lower biosimilar price point. "Positioning bsUST as a first line of treatment appears to be cost effective and an efficient alternative from the NHS perspective in Spain," they wrote, adding that "bsUST may significantly impact Crohn disease management in Spain, improving patient access due to its lower drug acquisition costs."

The study carried several limitations. Markov models assume transition probabilities depend only on the current health state, which may not fully capture the influence of prior treatment history. Efficacy for third- and fourth-line treatments was estimated by carrying forward second-line biologic-experienced data, a conservative approach driven by limited available data. The number of analyzed sequences, while validated by expert gastroenterologists, did not capture all possible treatment pathways. Additionally, the existence of a dual pricing system in Spain, with confidential reimbursement prices negotiated separately from official list prices, means that actual per-sequence costs in practice could differ from those modeled.

Rodríguez-Lago I, Peinado-Fabregat JI, Guigini M, Cerezales M, Ibáñez F, Crespo C, Barreiro-de Acosta M. Cost-effectiveness analysis of sequential treatment strategies for moderate to severe Crohn's disease in Spain: where should biosimilar ustekinumab be positioned? 

 2026;10:557-566. doi:10.1007/s41669-026-00642-1

D'Amico F, Bencardino S, Gonçalves A, et al. Unlocking hope: the future of ustekinumab biosimilars in Crohn's disease treatment. 

 2025;13(2):186-200. doi:10.1002/ueg2.12682

Early use of ustekinumab biosimilars in Spain shows cost-effective Crohn disease care, boosting QALYs and cutting NHS spend—insights for Europe.

Positioning Biosimilar Ustekinumab Early Reduces Burden on Spain's National Health System

Wide variation in how countries define, evaluate, and approve biosimilar medications may be undermining access to more affordable biological treatments—and a new comparative analysis lays out exactly where those gaps are widest.

Global review reveals uneven biosimilar rules on waivers, interchangeability, and safety tracking—barriers to cheaper biologics and approvals. | Image credit: Tex vector - stock.adobe.com

 examined biosimilar regulatory frameworks across all 6 World Health Organization (WHO) regions, finding persistent inconsistencies in how countries approach comparability requirements, clinical study waivers, interchangeability designation, and pharmacovigilance—differences that may complicate the approval process and limit medication availability.

Why Regulatory Divergence Matters for Biosimilar Access

Clinicians and policymakers who review biosimilar data from other countries often assume those data were produced under standards similar to their own. That assumption, the researchers noted, may be incorrect—and acting on it could introduce bias about a biosimilar's validated safety and efficacy profile. Although the WHO, FDA, and European Medicines Agency (EMA) have each issued guidance frameworks, countries have adopted them unevenly. The need to map those differences systematically became the foundation of the review.

That concern is not new to the field. A 2025 descriptive review 

Therapeutic Innovation & Regulatory Science

 examined individual national regulatory requirements and guidelines for biosimilars in more than 70 countries as of July 2024—including both emerging countries and those with extensive biosimilar experience—and similarly identified key differences that complicate global development efforts.

 Together, the 2 analyses paint a consistent picture of a regulatory landscape that has yet to cohere around shared standards.

The present scoping review followed PRISMA Extension for Scoping Reviews (PRISMA-ScR) methodology, searching CINAHL, PubMed, and Scopus databases through March 1, 2026, and drawing on 37 regulatory guidance documents from 19 countries.

 Twelve were classified as emerging and developing economies and 7 as advanced economies by the International Monetary Fund. The advanced economies—Canada, France, Germany, Japan, South Korea, the UK, and the US—served as comparators given their longer histories of biosimilar development. Emerging and developing economies spanned all 6 WHO regions, including Brazil, China, Egypt, India, Indonesia, Mexico, Nigeria, the Philippines, Poland, Saudi Arabia, Tanzania, and Turkey. No patient demographic data were collected, as the study examined regulatory documents rather than clinical outcomes.

Where Countries Agreed—and Where They Didn't

Most countries (n = 17 of 19; 89%) had adopted WHO biosimilar terminology, and the same proportion defined biosimilarity as the absence of meaningful differences in quality, safety, and efficacy compared with the reference product. Sixteen countries explicitly required comparability exercises, although Mexico, Indonesia, and China did not clearly include this requirement.

Gaps widened on more complex regulatory questions. All 7 advanced economies allowed waivers of clinical efficacy and immunogenicity testing when sufficient analytical data were available—consistent with updated 2022 WHO guidance. Among emerging and developing economies, only a subset had adopted comparable waiver policies, with Tanzania still requiring clinical efficacy studies in every case.

Interchangeability guidance, which determines whether a biosimilar can be substituted for its reference product, sometimes at the pharmacy level without physician consultation, appeared in the guidance documents of only 2 of the 12 emerging and developing economies studied: Nigeria and Poland. Nigeria's guidance, notably, explicitly discouraged substitution, citing pharmacovigilance concerns.

"These findings highlight areas in which the global regulatory framework requires greater harmonization to optimize access to biosimilar medications and to improve support for policy research and cross-country comparisons," the authors wrote.

Pharmacovigilance and Naming Requirements Add Complexity

Eleven countries required a pharmacovigilance plan as part of a biosimilar application. Japan, the Philippines, and the Republic of Korea were the only countries that explicitly mandated postmarketing pharmacovigilance studies. Guidance on biosimilar naming and labeling—important for adverse event tracking—was present in only 8 of the 19 countries examined.

Some official guidance documents were only available in their country's native language, creating the possibility of translation errors despite the use of DeepL Translate software. The researchers also could not confirm they had captured every official guidance document, as some countries distribute regulatory requirements across multiple publications. Guidance documents drafted but not made publicly available would not have been captured. Additionally, Indonesia was reclassified from the WHO South-East Asia region to the Western Pacific region in mid-2025, although all 6 WHO regions remained represented in the final analysis.

For US payers and managed care organizations tracking global biosimilar pipelines, the findings underscore the risk of equating international biosimilar evidence with FDA-reviewed data. The study also signals opportunity: the FDA's June 2024 draft guidance eliminating the requirement for switching studies, and its November 2025 draft guidance reducing the need for comparative clinical efficacy data in favor of analytical justifications, may position the US as a potential model for streamlined approval that other national regulatory agencies could follow.

Watanabe JH, Strand MW, Walvekar M, Alfonso-Cristancho R. Regulatory definitions and classification of biosimilar medications across the 6 regions of the World Health Organization: a scoping review. 

. 2026;7(5):e261642. doi:10.1001/jamahealthforum.2026.1642

Kirchlechner TM, Cohen HP. Global harmonization of biosimilar development by overcoming existing differences in regional regulatory requirements — outcomes of a descriptive review. 

. 2025;59(2):245-255. doi:10.1007/s43441-024-00740-4

Global review reveals uneven biosimilar rules on waivers, interchangeability, and safety tracking—barriers to cheaper biologics and approvals.

Global Biosimilar Rules Diverge Across WHO Regions, Limiting Patient Access

Most people with multiple sclerosis had never heard of biosimilars—even while taking them—a new Italian study reveals, raising urgent questions about patient education gaps in MS care.

The study findings revealed the substantial—yet largely untapped—role of MS nurses in shaping patient knowledge and therapeutic decision-making. | Image Credit: © Robert Kneschke - stock.adobe.com

Biosimilar Blindspot: Over 60% of MS Patients Reported No Prior Awareness

Despite the growing availability and clinical adoption of biosimilar therapies for multiple sclerosis (MS), a large majority of people actively treated with these agents had never heard of them before beginning therapy, according to the cross-sectional study 

. The finding underscores a significant informational deficit that may be shaping—and limiting—biosimilar acceptance across the MS care continuum.

Biosimilar therapies have emerged as a central strategy for improving affordability and expanding patient access to high-cost biologic treatments, including agents used in relapsing forms of MS. The recent approval of biosimilar natalizumab (studied in the Antelope phase 3 trial, 

 Yet patient resistance to initiating or switching to biosimilars remains a documented challenge—one that researchers increasingly attribute not to entrenched opposition but to gaps in health literacy and what is known as the nocebo effect, wherein negative expectations drive perceived adverse outcomes.

To better understand how informational experiences and health literacy shape biosimilar acceptance in this population, researchers in Italy conducted a multicenter observational study using a newly developed, theory-informed questionnaire structured around 4 health literacy domains: access, understand, appraise, and apply.

Italian study finds most MS patients start biosimilars unaware, exposing education gaps and highlighting MS nurses as key to boosting trust and uptake.