Based on findings from the ROSALIA study, the FDA has accepted for review a proposed denosumab biosimilar for patients with osteoporosis and treatment-related bone loss in patients with cancer.
The FDA has accepted a biologics license application (BLA) for a proposed denosumab (Prolia; Xgeva) biosimilar as a treatment for patients with osteoporosis and patients with cancer who have treatment-related bone loss, according to Sandoz, Inc.1
In the application, denosumab is indicated for treating patients with osteoporosis in postmenopausal women and in men at increased risk of fractures, treatment-induced bone loss, prevention of skeletal-related complications in cancer that has spread to the bone, giant cell tumor of the bone, and treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.
The submission and acceptance of this BLA is supported by findings from the phase 1/3 ROSALIA study (NCT03974100) which showed that the proposed biosimilar denosumab had comparable pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity in postmenopausal women with osteoporosis when compared with the reference medicine. Additionally, the agent supports demonstration of similarity, which is the basis for use in all indications.
“In addition to being an important medicine for cancer of the bone, denosumab is critical in the treatment of osteoporosis and potential prevention of osteoporosis-related fractures that so many women over 50 are at risk of,” Keren Haruvi, president of Sandoz United States and head of North America, said in a press release. “We are proud to be among the first to submit a BLA for a denosumab biosimilar as, if approved, it could increase patient access to an affordable, high-quality, potentially disease-modifying treatment across the [United States], while also delivering savings for health-care systems.”
Denosumab is a human monoclonal antibody created to bind to the RANKL protein. This protein is an activator of osteoclasts or cells that work to break down bone tissue. Denosumab reduces the activity of osteoclasts, resulting in less bone loss, fractures, and other serious bone conditions.
Previously, denosumab was approved for an expanded indication by the European Commission for the prevention of skeletal-related events (SREs) in adult patients with multiple myeloma. Then in May 2018, the FDA approved denosumab for the treatment of glucocorticoid-induced osteoporosis.2 The basis of this approval came from findings of a phase 3 study where denosumab elicited greater gains in bone mineral density when compared with risedronate (Actonel) in patients who were given prior treatment with glucocorticoid therapy.
Most recently on September 19, 2022, the company announced that the ROSALIA trial met its primary end points.1
In the multicenter, randomized, parallel arm, double-blind ROSALIA trial, 527 postmenopausal women with osteoporosis were randomized to receive either the biosimilar for denosumab or the reference product for up to 78 weeks of treatment. End points of the study were to show similar efficacy in terms of change in lumbar spine bone mineral density, pharmacokinetics, and pharmacodynamics. Investigators also assessed adverse events and serious adverse events in this patient population.3
Postmenopausal women between the ages of 55 and 80 with a diagnosis of osteoporosis, and body weight ≥ 50 kg and ≤ 90 kg at screening were enrolled in the study. Patients were required to have an absolute bone mineral density consistent with T-score ≤ -2.5 and ≥ -4.0 at the lumbar spine as measured by DXA, and at least 2 vertebrae in the L1-L4 region and at least 1 hip joint evaluable by DXA.