FDA Approves Celltrion’s Denosumab Biosimilars for Bone Loss Indications

On March 3, 2024, the FDA approved denosumab-bmwo under the names Stoboclo and Osenbelt, Celltrion’s denosumab biosimilar for all approved reference indications, including osteoporosis and other forms of bone loss.1 The biosimilars are expected to become available in the United States in June 2025.

"Denosumab is used to improve or protect bone health in patients with osteoporosis or those undergoing various cancer treatments and as a therapy for a lifetime for postmenopausal osteoporosis (PMO) patients," Jean-Yves Reginster, MD, PhD, professor of medicine, protein research chair, biochemistry department, college of science at King Saud University, Riyadh, Kingdom of Saudi Arabia and Director WHO Collaborating Centre for Epidemiology of Musculoskeletal Health and Aging, Liège, Belgium, said in a statement.1 "Biosimilars have expanded into new therapeutic areas such as immunology, oncology and ophthalmology as they continue to offer significant cost-saving potential while expanding patient access. Having a denosumab product with a clinically proven track record in quality and safety is a valuable addition for my patients."

Celltrion previously presented data supporting the approval of denosumab-bmwo at November’s American College of Rheumatology meeting in Washington, DC, in 2 presentations demonstrating immunogenicity and outcomes and efficacy and safety in postmenopausal women with osteoporosis presented by Reginster.2,3

Both abstracts presented data from a phase 3 randomized controlled trial. The trial had participants randomized 1:1 to 60 mg of CT-P41 or denosumab-bmwo every 6 months in the first treatment period (TP1) at week 0 and 26. Before dosing at week 52, patients initially assigned to denosumab in TP I were re-randomized in a 1:1 ratio to continue denosumab or to switch to CT-P41 in TP II while patients assigned to CT-P41 in TP I continued treatment with CT-P41. Data reported are from efficacy and safety follow-up up to Week 78 in TP II.

One abstract focused on immunogenicity and found no impact of anti-drug antibody (ADA) status on pharmacokinetics, efficacy, or safety in any of the study groups.2 The other demonstrated that the mean percent change of bone mineral density (BMD) for the lumbar spine, total hip, and femoral neck increased from baseline until week 78 comparably among denosumab-bmwo and reference denosumab groups.3

One patient (0.5%) had a new vertebral fracture in the CT-P41 maintenance group at Week 78. Nonvertebral fractures were reported in 2 (0.9%) patients in the CT-P41 maintenance group and 1 (1.0%) patient in the switch to CT-P41 group. No hip fracture was reported.3

There were no notable safety issues following the transition from denosumab to CT-P41. Around half of all participants (n = 211; 50.1%) experienced at least 1 treatment-emergent adverse event (TEAE), specifically 112 (50.9%) of the CT-P41 maintenance group, 42 (42.0%) of the denosumab maintenance group, and 57 (56.4%) of the switched to CT-P41 group. Rates of at least 1 serious TEAE were 2.6% in the CD-P41 maintenance group, 3.6% in the denosumab maintenance, and 0% in the switch to CT-P41 group.3

"The approval of STOBOCLO and OSENVELT is another step forward in our efforts to deliver cost-effective and high-quality treatments that address critical unmet needs in osteoporosis-related fracture as well as cancer-related skeletal events," Thomas Nusbickel, chief commercial officer at Celltrion USA, added.1 "Patients deserve therapeutic options that have the potential to make real impacts on their care and their lives. We are committed to continuous innovation to meet these goals leveraging our experience and successful track record with biosimilar and novel biologics."

REFERENCES

1. Celltrion receives U.S. FDA approval for STOBOCLO® (denosumab-bmwo) and OSENVELT® (denosumab-bmwo) biosimilars referencing PROLIA® and XGEVA®. News release. Celltrion. March 3, 2025. https://www.prnewswire.com/news-releases/celltrion-receives-us-fda-approval-for-stoboclo-denosumab-bmwo-and-osenvelt-denosumab-bmwo-biosimilars-referencing-prolia-and-xgeva-302390957.html

2. Reginster JY, Silverman SL, Czerwinski E, et al. Impact of Immunogenicity on Clinical Outcomes in Postmenopausal Women with Osteoporosis: Results from a Randomized Controlled Phase 3 Study to Compare CT-P41 (Proposed Denosumab Biosimilar) and Reference Denosumab. Presented at: ACR Convergence 2024; November 14-19; Washington, DC. Abstract 2144

3. Reginster JY, Silverman SL, Czerwinski E, et al. Efficacy and Safety Results of CT-P41 (Proposed Denosumab Biosimilar) Compared to Reference Denosumab in Postmenopausal Women with Osteoporosis: 78-Week Results from Phase 3 Randomized Controlled Trial. Presented at: ACR Convergence 2024; November 14-19; Washington, DC. Abstract 2563