Denosumab Biosimilar Demonstrates Equivalent Efficacy, Safety in Phase 3 Trial

Jean-Yves Reginster, MD, PhD

Credit: Rejuvenate Biomed

CT-P41, a proposed denosumab biosimilar, has demonstrated further favorable data compared to reference denosumab in postmenopausal women with osteoporosis.^1,2

These data were presented in 2 abstracts by Jean-Yves Reginster, MD, PhD, Outstanding Professor of Epidemiology, Public Health and Health Economics, and Professor of Bioethics and Societal Medicine, and Honorary Chair of the Bone and Cartilage Metabolism Unit, at the University of Liège, at the American College of Rheumatology (ACR) Convergence 2024, held November 14-19 in Washington, DC.

"We are excited to announce the additional evidence from the randomized controlled trial that further supports the biosimilarity between CT-P41 and reference denosumab in treating PMO," Hetal Patel, PharmD, MBA, Head of Medical Affairs at Celltrion USA, said in a statement.³ "These results further underline the capabilities of our dedicated biosimilar platform and anticipated diversification of our portfolio."

Both abstracts presented data from a phase 3 randomized controlled trial. The trial had participants randomized 1:1 to60 mg of CT-P41 or denosumab 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.¹

TP II included 422 participants randomized at Week 52 to CT-P41 maintenance (n = 221), denosumab maintenance (n = 100),or switch to CT-P41 (n = 101). Reginster and colleagues found 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 groups.¹

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.¹

Therewere no notable safety issues following thetransitionfrom 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. Four patients (1.8%) in the CT-P41 maintenance group experienced non-serious hypocalcemia. There was also one death, deemed unrelated to the study drug, in this group due to a TEAE of “genital neoplasm malignant female”.¹

The second 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

REFERENCES
1. 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

2. 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

3. Celltrion presents additional data from phase III randomized controlled trials to further support biosimilarity for CT-41 (biosimilar candidate of denosumab) and CT-P47 (biosimilar candidate of tocilizumab) at American College of Rheumatology (ACR) Convergence 2024. News release. Celltrion. November 18, 2024.