FDA Quietly Approves Denosumab Biosimilars, Issues Interchangeability for Others

The competitive landscape for biosimilar therapies targeting bone health and cancer-related skeletal events shifted markedly in fall 2025, as the FDA approved multiple denosumab biosimilars and issued 2 new interchangeability designations—signaling continued momentum in an increasingly crowded therapeutic space.

Denosumab Approvals Expand Market Access

The FDA approved several denosumab biosimilars referencing Prolia (for osteoporosis and bone loss) and Xgeva (for prevention of skeletal-related events in cancer) throughout 2025, with a surge of activity in the fall months.

In September 2025, the agency approved Hikma Pharmaceuticals/Gedeon Richter’s Enoby and Xtrenbo (denosumab-qbde), followed by approvals of Accord Healthcare’s Osvyrti and Jubereq (denosumab-desu) in October.1

These approvals represented a significant diversification in available denosumab options for both postmenopausal osteoporosis and oncology indications. Collectively, the biosimilars are expected to improve patient access and introduce pricing competition in a therapeutic area that has historically faced high treatment costs and limited alternatives.

Interchangeability for More Denosumab Products

Alongside the new approvals, the FDA formally granted the interchangeability (IC) designation to 2 pairs of denosumab biosimilars in late October 2025—a regulatory milestone allowing pharmacists to substitute these products for their reference biologics without prescriber approval, subject to state laws.

On October 29, 2025, Fresenius Kabi announced that its products Conexxence and Bomyntra were designated as interchangeable biosimilars to Prolia and Xgeva, respectively.2 Conexxence is indicated for adults at high risk for fracture, including individuals with osteoporosis, while Bomyntra is approved to prevent skeletal-related events in patients with multiple myeloma or bone metastases from solid tumors.

One day later, Celltrion announced the same designation for Stobocclo and Osenvelt (denosumab-bmwo), which are also interchangeable with Prolia and Xgeva across all approved indications.3 These designations were supported by analytical and comparative clinical data—including pharmacokinetic, safety, and immunogenicity results from studies in postmenopausal women with osteoporosis—demonstrating no clinically meaningful differences from their reference products.

According to Celltrion, the interchangeability status underscores the company’s commitment to expanding access to affordable biologic therapies while maintaining rigorous evidence-based standards for biosimilarity.

Designations Continue Amid Policy Confusion

The FDA’s decision to continue granting interchangeability designations came just weeks after federal officials publicly stated that all biosimilars should be considered interchangeable—a move that generated both optimism and confusion across the health care sector.

At an October 2025 press conference introducing new FDA draft guidance, HHS Secretary Robert F. Kennedy Jr, FDA Commissioner Marty Makary, MD, and Mehmet Oz, MD, asserted that “all biosimilars are interchangeable” with their reference products.4 The officials framed this position as an effort to streamline access, reduce costs, and encourage automatic pharmacy substitution, urging state governors to promote biosimilar adoption.

However, despite these declarations, the FDA has not officially retired the formal interchangeability designation process. The October approvals demonstrate that the agency continues to issue designations based on submitted evidence, consistent with statutory requirements under the Biologics Price Competition and Innovation Act.

Although the FDA’s recent draft guidance allows manufacturers to use existing Biologics License Application data to support interchangeability requests—reducing the need for costly switching studies—the broader legal framework for biosimilar substitution remains unresolved.

Officials have not clarified whether state-level restrictions on automatic substitution will be overridden by federal guidance. Currently, 4 states and Puerto Rico prohibit automatic biosimilar substitution, and many others require prescriber or patient notification. Without explicit federal preemption, the practical impact of “universal interchangeability” claims remains uncertain for pharmacy-dispensed biologics.

The denosumab approvals and interchangeability decisions align with the FDA’s ongoing efforts to modernize biosimilar development. The agency’s updated draft guidance—Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies—emphasizes advanced analytical methods over routine comparative efficacy trials. This approach is intended to shorten development timelines and reduce program costs, historically estimated at $100 million to $300 million per biosimilar.

For managed care stakeholders, these regulatory and policy shifts may offer faster, more cost-effective biosimilar entry into the US market. Yet, experts caution that the full benefits of these reforms will depend on broader systemic alignment—addressing persistent challenges such as manufacturing complexity, payer incentives, and pharmacy benefit manager transparency.

Despite progress, analysts warn that a “biosimilar gap” persists: only about 10% of biologics expected to lose exclusivity between 2025 and 2034 currently have biosimilars in active development. As denosumab biosimilars continue to reach the market, sustained collaboration among regulators, manufacturers, and payers will be key to achieving long-term affordability and access in biologic care.

References

1. Biosimilar approvals. The Center for Biosimilars®. Updated November 12, 2025. Accessed November 13, 2025. https://www.centerforbiosimilars.com/biosimilar-approvals

2. FDA grants interchangeable designation to Fresenius Kabi’s biosimilars Conexxence and Bomyntra (denosumab-bnht). News release; Fresenius Kabi. October 29, 2025. Accessed November 13, 2025. https://www.fresenius-kabi.com/us/news-and-events/interchangeable-designation-granted-conexxence-bomyntra

3. U.S. FDA grants interchangeability designation to Celltrion's denosumab biosimilars, Stoboclo (denosumab-bmwo) and Osenvelt (denosumab-bmwo). News release; Celltrion. October 30, 2025. Accessed November 13, 2025. https://www.prnewswire.com/news-releases/us-fda-grants-interchangeability-designation-to-celltrions-denosumab-biosimilars-stoboclo-denosumab-bmwo-and-osenvelt-denosumab-bmwo-302599537.html

4. Jeremias S. A closer look at new FDA guidance removing barriers to biosimilar development. The Center for Biosimilars. October 30, 2025. Accessed November 13, 2025. https://www.centerforbiosimilars.com/view/a-closer-look-at-new-fda-guidance-removing-barriers-to-biosimilar-development