Julia Bonavitacola

In HER2-positive breast cancer, pertuzumab remains a cornerstone therapy, but its price has limited access in some markets, underscoring the need for biosimilar alternatives that can maintain clinical confidence while expanding affordability.

A new study confirms KM118, a proposed biosimilar to pertuzumab, shows pharmacokinetic similarity and safety, paving the way for affordable HER2-positive breast cancer treatments. | Image credit: Romolo Tavani - stock.adobe.com

KM118, a proposed biosimilar to reference pertuzumab (Perjeta; Genentech, Inc.), was evaluated in a phase 1 pharmacokinetic study designed to support regulatory approval in China.

 was conducted to determine whether KM118 demonstrated pharmacokinetic similarity to the reference product and to assess its safety, tolerability, and immunogenicity in healthy participants, key requirements under international biosimilar development guidelines.

The randomized, double-blind, single-center, parallel-group study enrolled 100 healthy adult men in China. Participants were randomly assigned in a 1:1 ratio to receive a single 420-mg intravenous dose of either KM118 or reference pertuzumab. This fixed dose reflected established pertuzumab dosing and aligned with prior pharmacokinetic research. Blood samples were collected through 84 days after administration to characterize drug exposure, whereas safety and immunogenicity were monitored throughout the study period.

All participants were male, with a mean age of approximately 32 years and a mean body mass index of 22.9 kg/m². Most participants identified as Han Chinese, with a small number from other ethnic backgrounds. Individuals with clinically significant medical conditions, prior monoclonal antibody exposure, or evidence of pre-existing anti-drug antibodies were excluded, ensuring a relatively homogeneous and healthy study population suitable for detecting pharmacokinetic differences.

The primary pharmacokinetic endpoint was the area under the concentration–time curve from time 0 to the last measurable concentration (AUC₀–t). Biosimilarity was prespecified as a 90% confidence interval for the geometric mean ratio between test and reference products falling within the standard equivalence range of 80% to 125%. Secondary endpoints included maximum concentration (Cmax), AUC extrapolated to infinity (AUC₀–∞), and additional pharmacokinetic parameters.

Results showed closely aligned pharmacokinetic profiles between KM118 and reference pertuzumab. The geometric mean AUC₀–t was 74,465.82 ng·h/mL in participants receiving KM118 and 69,097.83 ng·h/mL in those receiving reference pertuzumab. The geometric mean ratio for AUC₀–t was 107.07%, with a 90% confidence interval of 99.92% to 114.72%, meeting the predefined biosimilarity criteria. Similarly, the confidence intervals for Cmax and AUC₀–∞ also fell within the accepted equivalence range, supporting overall pharmacokinetic similarity between the products.

Safety findings were consistent with expectations for pertuzumab exposure in healthy individuals. Most adverse events were grade 1 or 2 in severity, and no serious adverse events or grade 3 or higher events were reported. The most frequently observed events included laboratory abnormalities such as elevated triglycerides or uric acid, along with diarrhea and upper respiratory tract infections. The incidence and pattern of adverse events were comparable between treatment groups, suggesting no new safety signals associated with the biosimilar candidate.

Immunogenicity analyses showed similar rates of anti-drug antibody development between the 2 groups. Approximately 28% of participants tested positive for antidrug antibodies at the final assessment, with comparable proportions in the KM118 and reference arms. Neutralizing antibodies were rare, detected in only 1 participant. Although participants who developed antibodies had somewhat lower drug exposure and shorter half-lives, these findings were consistent with prior pertuzumab studies and did not differ meaningfully by treatment group.

The authors noted several limitations relevant to interpretation and payer decision-making. The study population included only healthy male participants, which limited generalizability to women and to individuals with breast cancer who may have comorbidities or receive combination therapies. In addition, the phase 1 design focused on pharmacokinetics rather than clinical efficacy, necessitating confirmatory phase 3 trials in patients with HER2-positive breast cancer to establish therapeutic equivalence.

Overall, the findings demonstrated pharmacokinetic biosimilarity between KM118 and reference pertuzumab, with comparable safety and immunogenicity profiles in healthy adults. For managed care stakeholders, these results represented an early but important step toward expanding biosimilar competition in the HER2-targeted therapy space, with the potential to improve access and moderate oncology drug spending pending further clinical confirmation.

Jeremias S. FDA approves poherdy: first interchangeable biosimilar to Perjeta. The Center for Biosimilars

. November 18, 2025. Accessed January 28, 2026. 

https://www.centerforbiosimilars.com/view/fda-approves-poherdy-first-interchangeable-biosimilar-to-perjeta

Li Y, Wang Y, Yang C, Zhao N, Wang X. A phase I, randomized, double-blind, parallel, single-dose pharmacokinetic study to evaluate the biosimilarity of KM118 (proposed pertuzumab biosimilar) with reference pertuzumab (Perjeta) in healthy male subjects. 

. 2025;57(1):2523561. doi:10.1080/07853890.2025.2523561

Articles

A new study confirms KM118, a proposed biosimilar to pertuzumab, shows pharmacokinetic similarity and safety, paving the way for affordable HER2-positive breast cancer treatments.

Early Evidence Supports KM118 as a Biosimilar to Reference Pertuzumab

For people who rely on insulin every day, even small changes can carry outsized weight, a reality that has complicated efforts to expand use of lower-cost biosimilar insulins across health systems.

 More than a decade after biosimilar insulins entered the market, uptake has grown slowly, shaped not only by regulatory frameworks and pricing policies but also by the perceptions and experiences of those most directly affected by switching.

globe health | Image credit: C Malambo:peopleimages.com - stock.adobec.om

, sought to clarify how health care professionals, people treated with insulin, and health service administrators have viewed and experienced switches from reference insulin products to biosimilars, highlighting persistent gaps in evidence relevant to managed care decision-making.

Biosimilar insulins have been available since 2014 and are approved on the basis of rigorous comparability exercises demonstrating similar quality, efficacy, and safety to reference products. Regulators in Europe, the UK, and the US have stated that biosimilars should be treated as interchangeable with their reference products, yet policies governing substitution and switching vary widely across jurisdictions.

 Despite the potential for meaningful savings in publicly funded and private health care systems, concerns about safety, efficacy, delivery devices, and patient acceptance have continued to limit broader adoption.

 The authors undertook this scoping review to map existing literature on stakeholder perceptions and experiences of biosimilar insulin switching and to identify where evidence remains sparse.

Using a systematic search of PubMed, Web of Science, and CINAHL Ultimate, supplemented by grey literature searches and reference scanning, the authors identified 184 records, with 20 meeting inclusion criteria. Eligible sources included quantitative and qualitative research studies, reviews, guidance documents, and opinion pieces published in English since 2014. Stakeholders of interest were health care professionals (HCPs), health service administrators (HSAs), and people of any age treated with insulin. Findings were synthesized narratively using thematic analysis rather than pooled quantitative outcomes, reflecting the heterogeneity of the literature.

Across multiple studies, awareness of biosimilar principles among HCPs was generally high, particularly among pharmacists. However, practical experience with switching was limited; in one survey, 67% of HCPs reported no direct experience switching people to biosimilar insulins. Levels of concern varied by profession. Diabetologists and nurses expressed higher levels of concern than pharmacists, particularly regarding efficacy and safety when switching established patients. In some studies, up to 32% of physicians and more than half of nurses reported major concerns about efficacy when switching.

Insulin-specific issues distinguished biosimilars from other therapeutic classes. Differences in pen devices, availability of connected or half-unit pens, and varying injection forces were frequently cited as barriers. HCPs also raised concerns about workload associated with education and monitoring after a switch, as well as skepticism toward pharmacy-level substitution without prescriber involvement. Although most HCPs acknowledged regulatory assurances of comparability, questions about long-term safety data and multiple switches between biosimilars persisted.

Evidence on patient perspectives was notably limited, with only 3 primary research studies identified from the US, Canada, and Japan. In a US survey examining a hypothetical future switch, most respondents expressed neutral or positive views toward biosimilar insulin, with only a small minority stating they would definitely refuse a switch. People with type 1 diabetes were slightly more hesitant than those with type 2 diabetes. Concerns centered on perceived brand quality, satisfaction with current therapy, and fears of reduced efficacy or safety.

Real-world experience data were sparse but informative. A Japanese study of people with type 2 diabetes who switched from reference to biosimilar insulin glargine reported no meaningful changes in treatment satisfaction, glycemic control, or adverse events. Similarly, a Canadian analysis of a mandatory switching policy found that only 2.8% of people switched back to the reference product, suggesting general tolerability of the transition.

Guidance directed at HSAs emphasized the need for structured switching programs, including clear criteria, education plans, and processes for informed consent. Administrators expressed concerns about legal responsibility, potential nocebo effects, and the logistical challenges of selecting among multiple biosimilars. Importantly, one Canadian study found no increase in health care resource utilization following mandatory switching, addressing a common concern that switches might drive additional clinical visits or monitoring costs.

Cost considerations were central across stakeholder groups, particularly in publicly funded systems such as the UK, where modest price differences sometimes limited enthusiasm for switching. In contrast, in settings where people bore more out-of-pocket costs, lower prices were a stronger driver of acceptance, though some individuals associated lower cost with lower quality. Factors expected to facilitate switching included robust real-world evidence, consistent education for HCPs and patients, endorsement from professional bodies, and shared decision-making approaches that allowed for switching back if needed.

The analysis did not assess study quality or quantify effect sizes, and the included literature was heterogeneous in design and geography. The authors noted a striking lack of data on stakeholders who had direct experience with biosimilar insulin switching, particularly outside a few high-income countries. As they concluded, “almost no literature related to the experience of stakeholders who have already engaged in biosimilar insulin switching was identified,” underscoring the need for pragmatic, real-world research to inform managed care policies.

For payers and health systems considering broader biosimilar insulin adoption, the findings suggest that clinical equivalence alone is insufficient. Addressing education gaps, device-related concerns, and the lived experiences of people treated with insulin will be critical to translating theoretical savings into sustainable practice.

1. Switching or deprescribing insulins: when & how. Enclara Pharmacia. June 23, 2022. Accessed January 19, 2026. 

https://enclarapharmacia.com/palliative-pearls/switching-or-deprescribing-insulins-when-how

2. Jeremias S. From Amjevita to Zarxio: a decade of US biosimilar approvals. The Center for Biosimilars

. March 6, 2025. Accessed January 19, 2026. 

https://www.centerforbiosimilars.com/view/from-amjevita-to-zarxio-a-decade-of-us-biosimilar-approvals

3. Hindley B, Wright S, Ooi C, Da Costa R, Cope L. Exploring stakeholder perceptions and experience of biosimilar insulin switching: a scoping review. 

 2026;9(1):e70142. doi:10.1002/edm2.70142

4. Biosimilar medicines can be interchanged. EMA. September 19, 2022. Accessed January 19, 2026. 

https://www.ema.europa.eu/en/news/biosimilar-medicines-can-be-interchanged

5. Guidance on the licensing of biosimilar products. UK MHRA. Accessed January 19, 2026. 

https://www.gov.uk/government/publications/guidance-on-the-licensing-of-biosimilar-products/guidance-on-the-licensing-of-biosimilar-products

6. Jeremias S. A closer look at new FDA guidance removing barriers to biosimilar development. The Center for Biosimilars. October 30, 2025. Accessed January 19, 2026. 

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

Explore the complexities of insulin biosimilars, their safety, and the impact on diabetes management in global health systems.

Perceptions Still Play a Central Role in Biosimilar Insulin Switching

The biosimilar landscape experienced significant expansion in late 2025, marked by crucial regulatory progress in Europe across immunology and bone health, alongside major strategic agreements positioning companies for key launches in the high-value North American oncology market. Recent news demonstrated how companies strengthened their portfolios by securing positive opinions from the Committee for Medicinal Products for Human Use (CHMP), announcing launches for high-demand therapies, and forging new alliances.

Doctor with patient | Image credit: Suteren Studio - stock.adobe.com

European Regulatory Momentum in Autoimmune Diseases

The European market saw 2 major biosimilar candidates receive positive recommendations from the CHMP, setting the stage for increased access to treatments for people living with chronic inflammatory conditions.

Celltrion received a positive CHMP opinion for the autoinjector presentation of SteQeyma (ustekinumab biosimilar). SteQeyma, a biosimilar to Stelara, was developed for the treatment of people with plaque psoriasis, psoriatic arthritis, and Crohn disease. The positive opinion specifically covered the 45-mg and 90-mg solutions for injection via autoinjector. The availability of the autoinjector option aimed to improve convenience and enhance the individual patient experience by expanding administration options. Celltrion noted that the autoinjector utilized a simple two-step administration process, which included clear visual and audible indicators to help people easily identify the injection status. The autoinjector formulation was also citrate-free and featured special thin-wall needle technology intended to reduce injection pain. This new administration option joined the currently approved presentations of SteQeyma, including pre-filled syringes and vials for subcutaneous injection, as well as concentrate for intravenous infusion.

In a separate announcement, STADA Arzneimittel and Bio-Thera Solutions received a positive CHMP opinion recommending approval for their biosimilar candidate, Gotenfia (golimumab).

 Gotenfia, which references Simponi, was recommended for marketing authorization for people with several chronic inflammatory autoimmune diseases. These conditions included rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, and ulcerative colitis in adult patients. The positive recommendation also covered juvenile idiopathic arthritis in people aged 2 years and older. Gotenfia was developed by Bio-Thera, who retained responsibility for manufacturing and supply, while STADA secured the exclusive rights for commercialization across the European Union, the UK, Switzerland, and other selected countries.

Expanding Access Through New Launches in Bone Health and Ophthalmology

Biosimilar launches in Europe broadened therapeutic access in bone health and ophthalmology, areas where current treatment costs place a high burden on health care systems.

Accord Healthcare announced the launch of 2 denosumab biosimilars following the scheduled expiration of the reference medicine’s patent on November 27, 2025.

 These launches included Osvyrti, a biosimilar referencing Prolia, and Jubereq, a biosimilar referencing Xgeva. Both medicines received approval from the European Medicines Agency in September 2025, after trials demonstrated they were highly similar to their reference products. Osvyrti, available as a 60-mg prefilled syringe, was indicated for the treatment of people with osteoporosis and bone loss linked to hormone ablation in men with prostate cancer.

Jubereq, available as a 120-mg vial, was indicated for the prevention of skeletal-related events in adults with advanced malignancies involving bone. Accord Healthcare stated that these biosimilars possessed the potential to provide treatment alternatives that helped lessen cost as a barrier for people accessing proven therapies.

Meanwhile, Sandoz announced the European launch of Afqlir (aflibercept), providing an affordable treatment option for people with retinal diseases.

 Afqlir, approved by the European Commission in November 2024, matched the reference medicine, Eylea, in efficacy, safety, and pharmacokinetics. The biosimilar, available as a 2-mg vial kit and pre-filled syringe for intravitreal injection, was indicated for the same indications as Eylea in adult patients.

Aflibercept is considered a gold standard treatment for various neovascular retinal diseases, which are leading causes of vision loss. The launch of Afqlir aimed to bring a high-quality, affordable aflibercept option for European people that maintains and improves vision while supporting more sustainable care across the region.

Strategic Partnership Targets US Oncology Market

Formycon AG and Zydus Lifesciences Limited cemented a partnership focused on penetrating the lucrative North American oncology biosimilar market.

 The companies jointly announced a strategic collaboration for the exclusive licensing and supply of FYB206, a biosimilar of Keytruda (pembrolizumab), in the US and Canada. Under the agreement, Formycon committed to finalizing development, preparing and filing the regulatory dossier, and supplying the product. Zydus assumed responsibility for the commercialization of FYB206 in both the US and Canada.

Pembrolizumab is a humanized monoclonal antibody used to treat various tumors, and its reference product, Keytruda, was one of the world’s best-selling drugs in 2024. Formycon anticipated receiving primary endpoint data from the clinical development phase of FYB206 in the first quarter of 2026, leading to the eventual submission of a biologics license application to the FDA. Zydus noted that this venture marked its entry into the North American biosimilar market, beginning with an immunotherapy product.

Sandoz launches Afqlir (aflibercept) in Europe, providing affordable treatment option for patients with retinal diseases. News release. Sandoz. November 11, 2025. Accessed December 18, 2025. 

https://www.sandoz.com/sandoz-launches-afqlirr-aflibercept-europe-providing-affordable-treatment-option-patients-retinal/

Golimumab biosimilar Gotenfia from STADA and Bio-Thera receives positive CHMP opinion. News release. Bio-Thera Solutions. December 12, 2025. Accessed December 18, 2025. 

https://www.prnewswire.com/news-releases/golimumab-biosimilar-gotenfia-from-stada-and-bio-thera-receives-positive-chmp-opinion-302640091.html

Accord Healthcare announces launch of denosumab - second biosimilar in bone health. News release. Accord Healthcare. December 2, 2025. Accessed December 18, 2025. 

https://www.prnewswire.com/news-releases/accord-healthcare-announces-launch-of-denosumab---second-biosimilar-in-bone-health-302629590.html

Celltrion receives positive CHMP opinion for SteQeyma (ustekinumab biosimilar) autoinjector. News release. Celltrion. December 18, 2025. Accessed December 18, 2025. 

https://www.celltrion.com/en-us/company/media-center/press-release/4348

Formycon and Zydus partner for exclusive licensing and supply agreement of FYB206, a biosimilar to Keytruda (Pembrolizumab), in the U.S. and Canada. News release. Formycon. December 9, 2025. Accessed December 18, 2025. 

https://www.globenewswire.com/news-release/2025/12/09/3202239/0/en/Formycon-and-Zydus-partner-for-exclusive-licensing-and-supply-agreement-of-FYB206-a-biosimilar-to-Keytruda-Pembrolizumab-in-the-U-S-and-Canada.html

Biosimilar partnerships and EU approvals surge, enhancing access to innovative treatments in immunology, oncology, and bone health markets.

Biosimilar Market Momentum: EU Approvals, Strategic Launches, and Major US Partnerships 

AVT06, a proposed biosimilar to aflibercept (Eylea; Regeneron Pharmaceuticals), demonstrated comparable efficacy, safety, and immunogenicity to the reference product in people with neovascular age-related macular degeneration (nAMD), according to a recently published phase 3 trial.

 The findings may help expand patient access to vision-preserving therapies by supporting regulatory approval of a lower-cost alternative.

AVT06, a promising biosimilar to Eylea, shows comparable efficacy and safety for treating neovascular age-related macular degeneration (AMD), enhancing patient access. | Image credit: Coetzee/peopleimages.com - stock.adobe.com

The trial was designed to address the high cost of biologic therapies such as aflibercept, which remain a barrier for many patients worldwide. Researchers sought to determine whether AVT06 could match the clinical benefits of aflibercept, a mainstay of treatment for nAMD, while offering a potentially more sustainable option for health systems.

AVT06 is currently under review with the FDA and the European Medicines Agency (EMA), with the EMA’s Committee for Medicinal Products for Human Use adopting a positive opinion recommending approval of AVT06 for several indications, including nAMD, and the European Commission still left to make a final decision.

The study was a double-masked, randomized, parallel-group, multicenter investigation conducted across 117 sites in 14 countries between June 2022 and September 2024. A total of 410 participants, all aged 50 years or older and diagnosed with treatment-naive nAMD, were enrolled. Participants were randomized 1:1 to receive intravitreal injections of AVT06 or reference aflibercept (2 mg) over 48 weeks, with follow-up at Week 52.

The primary endpoint was the change in best-corrected visual acuity at Week 8, measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores. Both groups achieved clinically meaningful gains in vision, with AVT06 showing a least squares mean change of 5.11 letters compared with 4.34 letters in the aflibercept group. The difference of 0.77 letters fell well within the pre-specified equivalence margin of –3.5 to 3.5 letters, confirming comparable efficacy. Sensitivity analyses reinforced these results.

Secondary outcomes, including changes in central subfield thickness, lesion size, and the presence of intraretinal or subretinal fluid, were also similar between treatment arms through week 52. Both groups maintained consistent improvements in retinal anatomy and vision across all timepoints.

The pharmacokinetic substudy revealed comparable systemic exposure for both treatments, with overall low concentrations supporting systemic safety. Immunogenicity testing found that, although antidrug antibodies (ADAs) and neutralizing antibodies developed in some participants, the overall rates were low and consistent with aflibercept’s established profile. Interestingly, the proportion of ADA-positive participants was numerically lower in the AVT06 group compared with the reference arm by week 52 (66.8% vs 80.5%).

Safety findings further underscored comparability. The incidence of treatment-emergent adverse events (TEAEs) was similar between groups—67.8% in AVT06 and 56.1% in the aflibercept arm—with most events being mild, transient, and unrelated to study treatment. Severe TEAEs were reported in 2% of AVT06 participants and 4.9% of aflibercept participants. Three deaths occurred during the trial, none deemed related to study drugs. The most frequently reported adverse events were nasopharyngitis and ocular events such as conjunctival hemorrhage and cataract.

The participant population had a mean age of 74 years, with balanced gender distribution (53.4% female, 46.6% male). The majority of participants were White (76.1%), with 6.8% Japanese and 16.3% Asian. Most participants (85.4%) presented with unilateral nAMD, and baseline vision was moderately impaired, averaging 55 ETDRS letters. Disease characteristics, including the presence of intraretinal and subretinal fluid, were comparable across groups.

The authors acknowledged several limitations. As a tightly controlled clinical trial, the study may not fully reflect outcomes in real-world practice, where adherence and monitoring can differ significantly. Additionally, the trial was not designed to evaluate cost-effectiveness directly, though the biosimilar pathway inherently aims to improve affordability.

In discussing the implications of the findings, the study authors noted, “The primary outcome of this study supports the demonstration of comparable efficacy of AVT06 and reference aflibercept, contributing to the totality of evidence needed for biosimilar approval.” They added that the results provide a strong foundation for potential extrapolation to other aflibercept-approved indications, such as diabetic macular edema and retinal vein occlusion.

The study’s rigorous design, international scope, and comprehensive evaluation of visual function, retinal anatomy, pharmacokinetics, and safety lend credibility to the findings. If approved, AVT06 could represent a meaningful addition to the ophthalmology biosimilar landscape, helping reduce financial barriers to care and broadening treatment access for people with nAMD and related retinal diseases.

1. Agostini H, Baumane K, Balčiūnienė, et al. A randomized, double-masked parallel-group, multicenter clinical study evaluating the efficacy and safety of the biosimilar candidate AVT06 compared to the reference product aflibercept in participants with neovascular age-related macular degeneration. 

. 2025;25(7):773-787. doi:10.1080/14712598.2025.2519531

2. European Medicines Agency recommends market approval of AVT06, Alvotech’s proposed biosimilar to Eylea (aflibercept). News release.  Alvotech. June 23, 2025. Accessed September 22, 2025. 

https://investors.alvotech.com/news-releases/news-release-details/european-medicines-agency-recommends-market-approval-avt06

3. Alvotech and Teva announce filing acceptance of U.S. biologics license application for AVT06, a proposed biosimilar to Eylea (aflibercept). News release. Alvotech. February 18, 2025. Accessed September 22, 2025. 

https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2025/Alvotech-and-Teva-Announce-Filing-Acceptance-ofU.S.-Biologics-License-Application-for-AVT06a-Proposed-Biosimilar-to-Eylea-aflibercept/default.aspx

AVT06, a promising biosimilar to aflibercept (Eylea), shows comparable efficacy and safety for treating neovascular age-related macular degeneration (AMD), enhancing patient access.

Proposed Aflibercept Biosimilar Shows Comparable Safety, Efficacy in Phase 3 AMD Trial

In September 2025, biosimilars continued to demonstrate their global impact, with AAM reporting $20.2 billion in US savings in 2024 despite a concerning development void, new FDA and European approvals expanding access to denosumab and aflibercept therapies, and real-world studies from Australia, Ireland, and China confirming that switching to biosimilars maintains safety and efficacy while reducing costs and enhancing patient access worldwide.

Biosimilar approvals surge in the US and Europe, enhancing access to denosumab and aflibercept therapies while driving significant health care savings.

AAM Report Reveals Startling Development Void Despite Biosimilar Success

Biosimilars generated $20.2 billion in savings in 2024 alone, contributing to a total of $56.2 billion since the first biosimilar entered the US market, according to the Association for Accessible Medicines (AAM).

 Collectively, generic and biosimilar medicines saved the US health care system $467 billion in 2024, adding to nearly $3.4 trillion in savings over the past decade. Increased biosimilar competition has expanded patient access, providing an estimated 460 million additional days of therapy, and second-to-market biosimilars entering within 3 years of the first have been shown to accelerate price reductions. However, the report highlighted a concerning “biosimilar void,” noting that 90% of biologics expected to lose patent exclusivity over the next decade currently lack a biosimilar in development.

The analysis also underscored ongoing challenges in the generics market. Generics made up roughly 90% of US prescriptions in 2024 yet only 12% of spending, with average out-of-pocket costs for generics remaining far below brand name drugs. Despite consistent savings, the report warned of price deflation creating unsustainable conditions for manufacturers. AAM leaders emphasized that coordinated action across manufacturers, providers, payers, and policymakers is essential to normalize biosimilar adoption, confront systemic barriers, and fully realize the cost and access benefits of these medicines.

American and European Biosimilar Approvals

The FDA has approved Bosaya (denosumab-kyqq) and Aukelso (denosumab-kyqq), marking the sixth pair of denosumab biosimilars cleared in the US.

 These approvals, granted to Biocon Biologics, expand affordable treatment options for patients with osteoporosis and cancer-related bone conditions. Bosaya, a biosimilar to Prolia, and Aukelso, a biosimilar to Xgeva, were both granted provisional interchangeability and demonstrated comparable quality, safety, and efficacy to their reference products.

Bosaya is indicated for postmenopausal women and men at high risk for fracture, glucocorticoid-induced osteoporosis, and certain patients receiving hormone ablation therapy for nonmetastatic prostate or breast cancer. Aukelso is approved to prevent skeletal-related events in multiple myeloma and bone metastases, treat giant cell tumors of bone, and manage refractory hypercalcemia of malignancy. These approvals continue a rapid expansion of denosumab biosimilars in the US, following 5 prior pairs that have launched since March 2024.

Following the US, the European Commission (EC) granted marketing authorizations for several new biosimilars, expanding affordable treatment options for patients with bone and retinal conditions.

 The approvals include 2 denosumab biosimilars, Bildyos and Bilprevda, from Organon and Shanghai Henlius Biotech, which are biosimilars to Prolia and Xgeva, respectively.

In addition, Germany-based STADA Arzneimittel received EC approval for Afiveg, an aflibercept biosimilar to Eylea, indicated for multiple retinal diseases including wet age-related macular degeneration. Afiveg marks STADA’s second ophthalmology biosimilar and eighth biosimilar overall in Europe, with a planned launch in Germany in Q4 2025. STADA executives emphasized the approvals as a way to expand patient access while supporting sustainable health care, building on the company’s growing specialty biosimilar portfolio.

Building Global Trust in Biosimilar Safety and Cost-Effectiveness

 highlighted the economic impact of biosimilars on the Australian health care system, demonstrating their role in reducing costs and driving price competition.

 Using a decade of sales data (2010-2020), researchers found that just 12 months after biosimilar entry, expenditure for reference biologics dropped by 38%, whereas per-unit prices fell 30% to 40%. Biosimilars themselves were priced up to 40% lower than reference products, and by 2020 they accounted for 30% of Australia’s biologics market. These findings emphasize that cost savings were primarily driven by price reductions rather than changes in overall use.

The study also underscored the importance of timing, policy, and clinician confidence for biosimilar adoption, with newer introductions like rituximab and trastuzumab capturing higher market shares than earlier entrants. Although patient-level uptake remains limited, with many unaware of biosimilar options, evidence shows that specialist recommendations strongly influence acceptance.

A prospective cohort study at Galway University Hospitals in Ireland found that patients with inflammatory bowel disease (IBD) who switched from reference adalimumab (Humira) to the biosimilar Amgevita (adalimumab-atto) maintained stable disease control and quality of life.

 Objective measures, including biomarkers and disease activity indices, showed no significant changes after the switch, and patient-reported symptoms improved slightly. Adverse events were generally mild, with only 2 patients reverting to Humira due to intolerance, and health anxiety was identified as a key predictor of perceived side effects.

The structured switching clinic also generated substantial cost savings, reducing drug expenditures by €143,958 over 8 weeks for the cohort, translating to an estimated €864,000 annually. Even after accounting for clinic costs and unscheduled care, net savings averaged €2,091 per patient. The study highlights that biosimilar switching can be safe, effective, and financially beneficial, particularly when accompanied by patient education and structured support to address psychological factors and optimize outcomes.

A real-world study from Fudan University Shanghai Cancer Center found that HLX02, a trastuzumab biosimilar, was as safe and effective as the originator in patients with HER2-positive metastatic breast cancer, including those who switched mid-treatment.

 Among 124 women, response rates and progression-free survival were comparable regardless of whether patients started on HLX02 or switched from Herceptin. Safety outcomes were consistent with prior clinical trials, and no new concerns emerged. The study reinforces HLX02 as a cost-effective option that could expand treatment access in resource-limited settings.

Recent regulatory and reimbursement milestones are broadening access to aflibercept biosimilars for retinal diseases worldwide.

 In the US, Sandoz settled patent disputes with Regeneron, clearing the path for Enzeevu to launch in late 2026. In Europe, Alteogen’s Eyluxvi received EC approval for multiple ophthalmic indications, demonstrating comparable efficacy and safety to Eylea in phase 3 trials. Meanwhile, Canada’s Ontario Drug Benefit Formulary added Biocon Biologics’ Yesafili, enabling public funding for over 2 million patients with retinal conditions. These developments collectively enhance global access to affordable, effective biosimilar therapies for vision-threatening diseases.

1. Jeremias S. Biosimilars drive savings and access, yet looming development gap threatens future. The Center for Biosimilars

. September 23, 2025. Accessed September 23, 2025. 

https://www.centerforbiosimilars.com/view/biosimilars-drive-savings-and-access-yet-looming-development-gap-threatens-future

2. Jeremias S. FDA approves Biocon Biologics' denosumab biosimilars: Bosaya and Aukelso. The Center for Biosimilars. September 18, 2025. Accessed September 22, 2025. 

https://www.centerforbiosimilars.com/view/fda-approves-biocon-biologics-denosumab-biosimilars-bosaya-and-aukelso

3. Jeremias S. EC approves new biosimilars for bone and eye conditions. The Center for Biosimilars. September 19, 2025. Accessed September 22, 2025. 

https://www.centerforbiosimilars.com/view/ec-approves-new-biosimilars-for-bone-and-eye-conditions

4. Jeremias S. Australian study reveals significant cost savings and market impact from biosimilars. The Center for Biosimilars. September 10, 2025. Accessed September 22, 2025. 

https://www.centerforbiosimilars.com/view/australian-study-reveals-significant-cost-savings-and-market-impact-from-biosimilars

5. Jeremias S. Switch to biosimilar adalimumab found safe and cost-saving for patients with IBD. September 9, 2025. Accessed September 22, 2025. 

https://www.centerforbiosimilars.com/view/switch-to-biosimilar-adalimumab-found-safe-and-cost-saving-for-patients-with-ibd

6. Jeremias S. Real-world evidence supports biosimilar HLX02 in metastatic breast cancer. The Center for Biosimilars. September 11, 2025. Accessed September 22, 2025. 

https://www.centerforbiosimilars.com/view/real-world-evidence-supports-biosimilar-hlx02-in-metastatic-breast-cancer

7. Jeremias S. Global aflibercept biosimilar progress signals rising access for retinal disease care. The Center for Biosimilars. September 22, 2025. Accessed September 22, 2025. 

https://www.centerforbiosimilars.com/view/global-aflibercept-biosimilar-progress-signals-rising-access-for-retinal-disease-care

Biosimilars News Roundup: September 2025

The competitive landscape for bone health treatments in the US has intensified with the 

 of Bildyos (denosumab-nxxp) and Bilprevda (denosumab-nxxp), biosimilars to Amgen’s reference products Prolia and Xgeva, respectively.

The FDA has approved 2 biosimilars, denosumab-nxxp (Bildyos) and (Bilprevda), referencing denosumab (Prolia) and denosumab (Xgeva), respectively, for use in all indications of the reference products. | Image Credit: gguy - stock.adobe.com

The approval, granted to Shanghai Henlius Biotech and Organon, marks the fifth pair of denosumab biosimilars to receive FDA clearance, promising to further expand access to more affordable treatment options for millions of patients facing osteoporosis and cancer-related bone complications. 

Denosumab is a crucial therapeutic agent, functioning as a human monoclonal antibody that binds to the RANKL protein, thereby preventing the activation of the RANK receptor on osteoclasts and inhibiting osteoclastic bone resorption. The reference products, Prolia and Xgeva, are widely used for various bone-related conditions, including osteoporosis, bone metastases, hypercalcemia of malignancy, and giant cell tumor of bone. The introduction of multiple biosimilars is expected to drive down costs and improve patient access.

The journey of denosumab biosimilars to the US market began relatively recently, with a flurry of approvals over the past year and a half:

Sandoz's Wyost and Jubbonti (denosumab-bddz for both) received FDA approval in March 2024, becoming the first biosimilars to reference Xgeva and Prolia, respectively, in the US.

Both Wyost and Jubbonti were also granted interchangeability designations with their reference products, allowing for pharmacy-level substitution without requiring prior physician approval. At the time of their approval, there were no denosumab biosimilars approved in the European Union. These biosimilars were the first denosumab biosimilars to launch in the US in June 2025.

In February 2025, Samsung Bioepis' Ospomyv and Xbryk (denosumab-dssb for both; SB16) gained approval from both the FDA and the European Medicines Agency (EMA).

 This pair also received an interchangeability designation and is currently "waiting in the wings to launch" in the US. Ospomyv references Prolia, and Xbryk references Xgeva.

Following this, the FDA approved Celltrion's Stoboclo and Osenvelt (denosumab-bmwo for both) on March 4, 2025. Stoboclo references Prolia, and Osenvelt references Xgeva. These biosimilars launched in the US in July 2025.

Fresenius Kabi's Conexxence and Bomyntra (denosumab-bnht for both) also received FDA approval in March 2025.

 Conexxence references Prolia, and Bomyntra references Xgeva. These biosimilars were approved for all indications of their respective reference products. Fresenius Kabi announced the commercial availability of these products in the US on July 1, 2025, and also plans to launch in Europe in the second half of 2025, pending regulatory approvals.

Henlius and Organon's Comprehensive Approval

The newest additions, Bildyos (denosumab-nxxp) and BILPREVDA (denosumab-nxxp), have been approved for all indications of their respective reference products.

 This broad approval was based on a comprehensive data package, including structural and functional analytical data, clinical pharmacokinetic data, and a comparative clinical study demonstrating that Bildyos and Bilprevda are highly similar to and have no clinically meaningful differences from their reference products, Prolia and Xgeva, respectively, in terms of safety, purity, and potency.

Bildyos, referencing Prolia, is indicated for:

Treatment of postmenopausal women with osteoporosis at high risk for fracture.

To increase bone mass in men with osteoporosis at high risk for fracture.

Treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture.

To increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer.

To increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. 

Bildyos is supplied as a 60 mg/mL injection. A boxed warning regarding severe hypocalcemia in patients with advanced chronic kidney disease (CKD), including those on dialysis, accompanies Bildyos, and treatment in these individuals should be supervised by a health care provider with expertise in CKD-MBD.

Bilprevda, referencing Xgeva, is approved for:

The prevention of skeletal-related events in patients with multiple myeloma and bone metastases from solid tumors. 

The treatment of giant cell tumor of bone in adults and skeletally mature adolescents where surgical resection is unresectable or likely to result in severe morbidity.

The treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. Bilprevda is available as a 120 mg/1.7 mL injection. 

Safety concerns for Bilprevda include hypersensitivity reactions, severe symptomatic hypocalcemia, osteonecrosis of the jaw, atypical subtrochanteric and diaphyseal femoral fractures, multiple vertebral fractures following treatment discontinuation, and embryo-fetal toxicity, necessitating effective contraception for females of reproductive potential. 

Although the sources highlighted interchangeability status for Sandoz's and Samsung Bioepis' products, there was no mention of an interchangeability designation for Henlius and Organon's Bildyos and Bilprevda in the provided information.

Jon Martin, US commercial lead for biosimilars and general medicines at Organon, emphasized the significance of these approvals, stating, "Our goal with these biosimilars is to improve access and affordability across multiple therapeutic areas, including for osteoporosis, which disproportionately affects women." 

Jason Zhu, PhD, executive director and CEO of Henlius, added that the approvals underscore their commitment to "expanding access to quality biologics... delivering biosimilar treatment options that are as safe and effective as the reference biologics to more patients across the US." 

1. Shanghai Henlius Biotech, Inc. US Food and Drug Administration (FDA) approves Henlius and Organon’s Bildyos (denosumab-nxxp) and Bilprevda (denosumab-nxxp), biosimilars to Prolia (denosumab) and Xgeva (denosumab), respectively-media. September 2, 2025. Accessed September 2, 2025. 

https://www.henlius.com/en/NewsDetails-5427-26.html

2. Jeremias S. FDA approves first denosumab biosimilars. The Center for Biosimilars

. March 5, 2024. Accessed September 2, 2025. 

https://www.centerforbiosimilars.com/view/fda-approves-first-denosumab-biosimilar

3. Jeremias S. Wyost and Jubbonti launch as first denosumab biosimilars in the US. The Center for Biosimilars. June 2, 2025. Accessed September 2, 2025. 

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

4. Jeremias S. Two more pairs of denosumab biosimilars enter US market. The Center for Biosimilars. July 9, 2025. Accessed September 2, 2025. 

https://www.centerforbiosimilars.com/view/two-more-pairs-of-denosumab-biosimilars-enter-us-market

5. Santoro C. FDA approves another pair of denosumab biosimilars, Conexxence and Bomyntra. The Center for Biosimilars. March 27, 2025. Accessed September 2, 2025. 

https://www.centerforbiosimilars.com/view/fda-approves-another-pair-of-denosumab-biosimilars-conexxence-and-bomyntra

New denosumab biosimilars, Bildyos and Bilprevda, enhance access to affordable osteoporosis and bone disease treatments, promising significant patient benefits.

FDA Greenlights Fifth Pair of Denosumab Biosimilars: Bildyos and Bilprevda

Alvotech, an Iceland-based biosimilar-focused biotech company, marked a significant financial milestone in the first half of 2025, swinging from a substantial loss to a net profit, driven by the strong commercial performance of its key biosimilar products.

 The company's financial results pointed to a more than 200% year-on-year increase in product revenues, which fueled its first-ever quarterly positive cash flow from operations.

Alvotech achieves a remarkable financial turnaround in 2025, reporting a net profit driven by strong biosimilar sales and strategic partnerships. | Image credit: vadish - stock.adobe.com

For the first 6 months of the year, Alvotech reported a net profit of $141.7 million, a stark reversal from the $153.5 million net loss it experienced during the same period in 2024. Total revenue for the period was $306 million, a 30% increase from the $236 million reported in the first half of 2024. This growth was largely attributed to a massive jump in product revenue, which surged to $204.7 million from just $65.9 million a year prior.

Alvotech Chairman and Chief Executive Officer Robert Wessman noted the momentum, stating that the results "confirm our business momentum and the opportunities that lie ahead." He added that new and expanded partnerships reflected the company's increased development activity. The company's cash and cash equivalents stood at $151.5 million as of June 30, 2025, bolstered by the robust operational performance.

The company's financial success was fueled primarily by the market expansion of its 2 approved biosimilars, a high-concentration adalimumab (Humira) biosimilar and an ustekinumab (Stelara) biosimilar. The adalimumab biosimilar, marketed as Simlandi in the US and Hukyndra in Europe, continued its strong sales trajectory. Simlandi received FDA approval as the first high-concentration, citrate-free interchangeable biosimilar to Humira in February 2024, a key advantage in the competitive US market.

The ustekinumab biosimilar, known as Selarsdi in the US and Uzpruvo in Europe, also contributed significantly to the revenue surge.

 After gaining interchangeable status from the FDA in April 2025, the product's market share in the US reached more than 20% of the overall Stelara market in July 2025, meeting the company's internal projections.

Beyond its launched products, Alvotech maintains a pipeline of biosimilar candidates for various therapeutic areas, including autoimmune disorders, eye disorders, and oncology. Several programs progressed this year, with some transitioning out of the clinical phase. The company's biologics license applications (BLA) for proposed biosimilars to Prolia/Xgeva (denosumab) and Eylea (aflibercept) were accepted by the FDA. The aflibercept biosimilar, now named Mynzepli, recently secured European approval, marking a critical step toward commercialization.

Alvotech also broadened its strategic partnerships, licensing European rights to 3 new biosimilar—referencing Ilaris (canakinumab), Kesimpta (ofatumumab), and an undisclosed biologic—from Advanz Pharma.

 A collaboration agreement was also established with Dr. Reddy's for AVT32, a biosimilar candidate to Keytruda (pembrolizumab).

To further bolster its research and development capabilities, Alvotech acquired Xbrane Biopharma’s research and development operations in Sweden in March 2025 for SEK 275 million (approximately $28.9 million).

Alvotech achieves a remarkable financial turnaround in 2025, reporting a net profit driven by strong biosimilar sales and strategic partnerships.

Julia Bonavitacola

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