Denosumab Biosimilars Approved by FDA for Previously Referenced Indications

The FDA has approved 2 denosumab biosimilars for all prior approvals for the reference drugs in patients with cancers and osteoporosis.

Denosumab-bmwo (CT-P41; Stoboclo) and denosumab-bmwo (CT-P41; Osenvelt) biosimilars have been approved by the FDA for all indications of previously referenced agents denosumab (Prolia) and denosumab (Xgeva), respectively, according to a press release from the developer, Celltrion.1

“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 [patients with] osteoporosis,” Jean-Yves Reginster, professor of Medicine, Protein Research Chair in Biochemistry Department at the College of Science, King Saud University in Riyadh, Kingdom of Saudi Arabia and the director of the World Health Organization Collaborating Centre for Epidemiology of Musculoskeletal Health and Aging in Liège, Belgium, stated in the press release.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.”

A double-blind, active-controlled, randomized phase 3 study (NCT04757376) that compared the efficacy, pharmacokinetics, pharmacodynamics, and safety of CT-P41 vs Prolia in postmenopausal women with osteoporosis supported the FDA’s decision.2 Patients who received CT-P41 experienced equivalent efficacy and pharmacodynamics, similar pharmacokinetics, and comparable safety vs those who received Prolia.

STOBOCLO

Stoboclo, a receptor activator of NF-κb ligand (RANKL) inhibitor, is currently considered therapeutically equivalent to Prolia. It is approved, in the US, to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer, to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer, to increase bone mass in men with osteoporosis at high risk for fracture, and to treat postmenopausal women with osteoporosis at high risk for fracture and glucocorticoid-induced osteoporosis in men and women at high risk for fracture.

In February 2025, Stoboclo was approved by the European Medicines Agency (EMA).

A 3-year, randomized multinational study evaluated the safety and efficacy of Stoboclo as a treatment for bone loss in patients with nonmetastatic prostate cancer receiving androgen deprivation therapy.3 Patients received subcutaneous injections of either 60 mg of denosumab once every 6 months for 6 doses (n = 734) or placebo (n = 734). At 3 years, treatment differences in bone mineral density with denosumab vs placebo were +7.9% at the lumbar spine, +5.7% at the total hip, and 4.9% at the femoral neck.

For patients with breast cancer, the efficacy and safety of Stoboclo in those receiving adjuvant aromatase inhibitor therapy were assessed in a 2-year, randomized, multinational study.3 Patients received subcutaneous injections of either 60 mg of denosumab once every 6 months for 4 doses (n = 127) or placebo (n = 125). At 2 years, treatment differences in bone mineral density were +7.6% at the lumbar spine, +4.7% at the total hip, and +3.6% at the femoral neck.

The most common adverse events with Stoboclo were bone loss due to hormone ablation for cancer in at least 10% of patients—more specifically arthralgia and back pain—though extremity and musculoskeletal pain have also been reported. Additionally, back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis occurred in patients with postmenopausal osteoporosis in more than 5% of patients; pancreatitis was also reported in this population. More than 5% of male patients with osteoporosis also experienced back pain, arthralgia, and nasopharyngitis. More than 3% of patients with glucocorticoid-induced osteoporosis experienced back pain, hypertension, bronchitis, and headache.

OSENVELT

Osenvelt, also a RANKL inhibitor, is considered therapeutically equivalent to Xgeva. In the US, Osenvelt is approved to treat adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity, to prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors, and to treat hypercalcemia of malignancy refractory to bisphosphonate therapy.

Osenvelt was approved by the EMA in February 2025.

Osenvelt was investigated in study 20050136 (NCT00321464) which evaluated the treatment in patients with advanced breast cancer and bone metastasis, in study 20050244 (NCT00330759) which evaluated the treatment in patients with solid tumors other than breast and castrate-resistant prostate cancer with bone metastasis and multiple myeloma, and in study 20050103 (NCT00321620) that evaluated the treatment in patients with castrate-resistant prostate cancer and bone metastasis.3

In at least 25% of patients with bone metastasis from solid tumors, the most common adverse reactions were fatigue or asthenia, nausea, and hypophosphatemia. At least 10% of patients with multiple myeloma experienced diarrhea, nausea, back pain, anemia, peripheral edema, thrombocytopenia, rash, headache, and upper respiratory tract infection. In at least 10% of patients with giant cell bone tumor, they were arthralgia, nausea, fatigue, back pain, headache, and pain in extremity. Additionally, nausea, decreased appetite, peripheral edema, headache, dyspnea, anemia, constipation, and diarrhea occurred in more than 20% of patients with hypercalcemia of malignancy.

Reference

1. Celltrion receives U.S. FDA approval for STOBOCLO® (denosumab-bmwo) and OSENVELT® (denosumab-bmwo) biosimilars referencing PROLIA® and XGEVA®. News release. Celltrion. March 4, 2025. Accessed March 5, 2025. https://tinyurl.com/ahnwrx57
2. A phase 3 study to compare between CT-P41 and US-licensed Prolia in postmenopausal women with osteoporosis. ClinicalTrials.gov. Updated June 14, 2024. Accessed March 4, 2025. https://tinyurl.com/mumw3my6
3. Prescribing information. STOBOCLO U.S. prescribing information. FDA. 2025. Accessed March 5, 2025. https://tinyurl.com/3axp9x9a