Two Denosumab Biosimilars Pocket FDA Approval in Multiple Indications
Two denosumab biosimilars have gained FDA approvals across multiple indications.
US FDA
The FDA has approved 2 biosimilars, denosumab-bmwo (CT-P41; Stoboclo) and (Osenvelt), for all indications of their respective reference products (Prolia) and (Xgeva), Celtrion stated in a news release.1 These indications include osteoporosis-related fractures and cancer-related skeletal events in both men and women across cancer types.
Data from a phase 3 trial (NCT04757376) evaluating efficacy, pharmacodynamics (PD), pharmacokinetics (PK), safety, and immunogenicity for CT-P41 provided the basis for this approval.2
Stoboclo is approved for several osteoporosis-related conditions in individuals at high risk for fractures. It is used to treat postmenopausal women with osteoporosis, increase bone mass in men with osteoporosis, and manage glucocorticoid-induced osteoporosis in both men and women. It helps improve bone mass in men undergoing androgen deprivation therapy for nonmetastatic prostate cancer and in women receiving adjuvant aromatase inhibitor therapy for breast cancer.1
Osenvelt is approved for several bone-related conditions associated with cancer. It helps prevent skeletal complications in individuals with multiple myeloma or bone metastases from solid tumors. It is used to treat adults and skeletally mature adolescents with giant cell tumors of the bone when surgery is not an option or would cause significant complications. Osenvelt is also indicated for managing hypercalcemia caused by cancer that does not respond to bisphosphonate therapy.1
“Denosumab is used to improve or protect bone health in patients with osteoporosis or those undergoing various cancer treatments and as a lifetime therapy for patients with postmenopausal osteoporosis,” said Jean-Yves Reginster, MD, PhD. “Biosimilars have expanded into new therapeutic areas such as immunology, oncology and ophthalmology as they continue to offer significant cost-saving potential and expanding patient access. Having a denosumab product with a clinically proven track record in quality and safety is a valuable addition for my patients.”1
Reginster is professor of medicine, protein research chair of the Biochemistry Dept, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia and director of WHO Collaborating Centre for Epidemiology of Musculoskeletal Health and Aging in Liège, Belgium.
In the double-blind, active-controlled phase 3 trial, 479 postmenopausal women with osteoporosis were randomly assigned to receive 60 mg subcutaneous CT-P41 or US reference denosumab in 1 of 2 treatment periods.2 At 52 weeks, those receiving US reference denosumab were randomly assigned 1:1 to continue treatment or switch to CT-P41 in the second treatment period.
The main measure of effectiveness was the percentage change in lumbar spine bone density after 52 weeks. The treatments were considered equally effective if the 95% CI for the difference in average group results stayed within the range of –1.503% to 1.503%.
CT-P41 and US reference denosumab were shown to be equally effective based on primary efficacy, with least squares mean differences of -0.14 (-0.83 to 0.55) in the full analysis set and -0.28 (-0.97 to 0.41) in the per-protocol set. PD results were also similar, with geometric least squares mean ratio of 94.94% (90.75% - 99.32%). Secondary efficacy, PD, PK, and safety were comparable across all groups up to week 78, including after switching from US reference denosumab to CT-P41.
A double-blind, 2-arm, parallel-group phase 1 trial (NCT06037395) evaluated PK equivalence of CT-P41 and US reference denosumab in healthy male patients.3 In the trial, 154 participants were assigned 1:1 to receive a single 60 mg subcutaneous dose of either CT-P41 or US reference denosumab. Equivalence was confirmed if the 90% CI for the ratios of geometric least-squares means fell within the predefined range (80%-125%).
Of the 151 participants who received treatment, PK, PD, safety, and immunogenicity results were comparable between the groups. The 90% CI for the area under the curve (AUC) and Cmax remained within the equivalence margin, with AUC0-inf at 100.4 to 114.7, AUC0-last at 99.9 to 114.3, and Cmax at 95.2 to107.3.3
“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,” said Thomas Nusbickel, chief commercial officer at Celltrion USA.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.”
