FDA Approves Amneal Denosumab Biosimilars, Capping Year of Market Expansion

The US biosimilar market officially capped off a high-stakes year for regulatory activity with a final expansion in the denosumab space. The FDA approved 2 new biosimilars from Amneal Pharmaceuticals, Boncresa (denosumab-mobz) and Oziltus (denosumab-mobz), which serve as lower-cost alternatives to the reference biologics Prolia and Xgeva, respectively.1 This move concluded a busy 12 months for the industry, marking the eighth pair of denosumab biosimilars—the ninth pair overall—to receive approvals in 2025.2

A Strategic Partnership for Market Growth

Amneal’s latest approvals were the result of a collaboration with mAbxience, a group majority-owned by Fresenius Kabi.1 Although mAbxience handled the development and manufacturing of the products, Amneal held the exclusive rights for commercialization in the US. This launch brought Amneal’s commercial biosimilar portfolio to 5 products, moving the company closer to its goal of having 6 biosimilars across 8 presentations by 2027.

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

Closing Out a "Banger Year" for Denosumab

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

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

Policy Shifts and Clinical Realities

While 2025 was a win for access, it was also a year of policy-related questions. Federal officials, including HHS Secretary Robert F. Kennedy Jr. and FDA Commissioner Marty Makary, MD, sparked an industrywide discussion by suggesting that all biosimilars should be considered interchangeable with their reference products to simplify the substitution process.3 Despite these statements, the FDA continued to issue formal IC designations based on statutory requirements, leaving some uncertainty regarding how state laws on automatic pharmacy substitution would eventually align with federal guidance.

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

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

Looking Ahead to the "Biosimilar Gap"

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

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

References

1. Amneal announces FDA approval of denosumab biosimilars referencing Prolia and Xgeva. News release. Amneal Pharmaceuticals. December 22, 2025. Accessed January 5, 2026. https://investors.amneal.com/news/press-releases/press-release-details/2025/Amneal-Announces-FDA-Approval-of-Denosumab-Biosimilars-Referencing-Prolia-and-XGEVA

2. Biosimilar approvals. The Center for Biosimilars®. Updated November 12, 2025. Accessed January 5, 2026. https://www.centerforbiosimilars.com/biosimilar-approvals

3. FDA quietly approves denosumab biosimilars, issues interchangeability for others. The Center for Biosimilars. November 13, 2025. Accessed January 4, 2026. https://www.centerforbiosimilars.com/view/fda-quietly-approves-denosumab-biosimilars-issues-interchangeability-for-others