Denosumab, Golimumab Biosimilars Clear Major Regulatory Milestones in Europe, as US Hurdles Remain

The final months of 2025 delivered a mix of significant victories and temporary setbacks for biosimilar developers in the global regulatory landscape, marked by multiple European approvals for biosimilars targeting blockbuster autoimmune and bone health treatments, while a manufacturing concern delayed a key entry into the competitive US market.

DNA syringe | Image credit: natali_mis - stock.adobe.com

Denosumab Biosimilars Flood European Economic Area Market

The European Economic Area (EEA) saw multiple approvals for biosimilars referencing Prolia and Xgeva (denosumab), opening the door to increased patient access and sustainable health care budgets.

Alvotech announced that the European Commission (EC) had approved AVT03 as a biosimilar to Prolia and Xgeva.¹ Denosumab is an established treatment widely used for managing osteoporosis and preventing skeletal-related events in people with certain cancers. The EC decision underscored Alvotech’s continuing progress across its biosimilar portfolio and highlighted its role as a partner to health systems across Europe. This approval demonstrated the strength of the company’s end-to-end platform and ability to deliver high-quality biosimilars to patients across Europe.

AVT03 was approved in 2 presentations: a 60 mg/mL single-use pre-filled syringe biosimilar to Prolia, intended for the treatment of osteoporosis and bone loss, and a 70 mg/mL single-use vial biosimilar to Xgeva, for preventing skeletal-related events in adults with advanced malignancies involving bone. The approval was based on a totality of evidence, including confirmatory clinical studies demonstrating equivalent efficacy and pharmacokinetics and comparable immunogenicity and safety to the reference product. The European denosumab market was valued at approximately US$1.2 billion across all indications, based on originator sales in the 12 months leading up to the second quarter of 2025.

Alvotech planned to commercialize AVT03 in partnerships with Dr. Reddy’s and STADA in the EEA, Switzerland, and the UK. STADA planned to market the product as Kefdensis (biosimilar to Prolia) and Zvogra (biosimilar to Xgeva), while Dr. Reddy’s intended to market it as Acvybra and Xbonzy, respectively.

In parallel, Teva Pharmaceutical Industries also received EC marketing authorizations for its 2 denosumab biosimilar candidates: Ponlimsi (biosimilar to Prolia) and Degevma (biosimilar to Xgeva).² The approvals followed a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) earlier in the year. Ponlimsi (60 mg/1 mL pre-filled syringe) was indicated for treating osteoporosis in postmenopausal women and men who are at increased risk of fractures, as well as for treating bone loss associated with hormone ablation in men with prostate cancer or in adults on long-term systemic glucocorticoid treatment. Degevma (120 mg/1.7 mL solution in a vial) was indicated for preventing bone complications in adults with advanced cancer involving bone and for treating adults and skeletally mature adolescents with giant cell tumor of bone. Teva emphasized that these product launches provided additional treatment options for healthcare systems throughout Europe, aligning with the company's Pivot to Growth strategy.

Golimumab Biosimilar Approved in Europe, Faces US Delay

Alvotech celebrated further regulatory success in Europe with its golimumab candidate, but simultaneously reported a key delay in the US regulatory pathway for the same product.

Alvotech and Advanz Pharma announced the EC granted marketing authorizations for Gobivaz (golimumab), a biosimilar to Simponi, for use across the EEA.³ This approval allowed for the treatment of various immune-mediated diseases in adults, including axial spondyloarthritis, rheumatoid arthritis, ulcerative colitis, and psoriatic arthritis. Significantly, Gobivaz also received authorization for treating juvenile idiopathic arthritis in children aged 2 years and older when used in combination with methotrexate. Alvotech provided the commercial supply and development of Gobivaz, while Advanz Pharma held the exclusive commercialization rights for the UK and the EEA.

Just weeks earlier, however, Alvotech announced that the FDA issued a complete response letter (CRL) for the biologics license application for its golimumab biosimilar candidate, AVT05.⁴ The CRL cited specific deficiencies that needed satisfactory resolution; these deficiencies had been conveyed following the FDA’s pre-license inspection of Alvotech’s Reykjavik manufacturing facility, which concluded in July 2025.

The facility remained approved to manufacture and continued supplying the currently commercialized products. Despite expressing disappointment in receiving the CRL, the company expected to resolve the outstanding issues. Following this regulatory action, Alvotech adjusted its 2025 total revenue outlook downward to $570 million to $600 million, primarily due to expected continuation of investments related to resolving the facility issues and a temporary slowdown in production. At the time of the announcement, the sources noted that no biosimilar to Simponi had received FDA approval.

References

1. Alvotech announces approval of AVT03, a biosimilar to Prolia and Xgeva (denosumab) in the European Economic Area. Alvotech. News release. November 24, 2025. Accessed December 16, 2025. https://www.globenewswire.com/news-release/2025/11/24/3193284/0/en/Alvotech-Announces-Approval-of-AVT03-a-Biosimilar-to-Prolia-and-Xgeva-denosumab-in-the-European-Economic-Area.html

2. Teva receives European Commission approvals for Ponlimsi (denosumab) biosimilar to Prolia and Degevma (denosumab) biosimilar to Xgeva. Teva Pharmaceutical Industries. News release. November 25, 2025. Accessed December 16, 2025. https://www.globenewswire.com/news-release/2025/11/25/3194303/0/en/Teva-receives-European-Commission-approvals-for-PONLIMSI-denosumab-Biosimilar-to-Prolia-and-DEGEVMA-denosumab-Biosimilar-to-Xgeva.html

3. Alvotech and Advanz announce EC approval for Gobivaz biosimilar. Pharmaceutical Technology. November 21, 2025. Accessed December 16, 2025. https://www.pharmaceutical-technology.com/news/alvotech-advanz-ec-approval

4. Alvotech provides update on the status of U.S. biologics license application for AVT05. Alvotech. News release. November 2, 2025. Accessed December 16, 2025. https://www.globenewswire.com/news-release/2025/11/02/3178815/0/en/alvotech-provides-update-on-the-status-of-u-s-biologics-license-application-for-avt05.html