FDA Accepts Organon’s Application for Prolia Biosimilar

The FDA has accepted the biologic license application (BLA) for HLX14, a biosimilar referencing Amgen’s Prolia/Xgeva (denosumab). Prolia treats men and women with osteoporosis and Xgeva treats patients with bone cancer.

Organon, which acquired the commercialization rights from Shanghai Henlius Biotech, anticipates hearing from regulatory authorities about the HLX14 application by mid-year 2025, according to a spokesperson.

Osteoporosis is a bone disease that develops when bone mineral density and bone mass decrease or when bone strength and structure change. More than 10 million U.S. adults aged 50 and over live with osteoporosis, a major cause of fractures in postmenopausal women and in older men.

Bone is the third most frequent site for metastatic tumors. Nearly all types of cancer can spread to the bone and cause pain and fractures, though cancers that often metastasize in bones include breast and prostate.

Denosumab is a human monoclonal antibody designed to bind to the RANKL protein, an activator of osteoclasts (cells involved in breaking down bone tissue). By inhibiting RANKL, denosumab decreases the production and activity of osteoclasts, resulting in a reduction of bone loss, the likelihood of fractures and other serious bone conditions.

The Organon/Shanghai Henlius Biotech application is based on data from a series of head-to-head studies for HLX14, including comparative quality analytical studies and two clinical studies. The first trial was a two-part phase 1 study in Chinese healthy adult men to compare pharmacokinetic parameters of HLX14 and EU-sourced Prolia. The second was a phase 3 clinical study comparing the efficacy, safety, tolerability, and immunogenicity of HLX14 with Prolia in postmenopausal women with osteoporosis at high risk for fracture.

In May 2024, Organon/Shanghai Henlius Biotech announced they had also submitted an application for the Prolia/Xgeva biosimilar to European regulators.

The U.S. application of HLX14 follows Teva’s application for its Prolia biosimilar candidate TVB-009P. The FDA’s decision for Teva’s product is also expected in the second half of the 2025. The application is based on an analytical and clinical data package including results from a phase 3 trial investigating the safety and efficacy of TVB-009P versus Prolia in women with postmenopausal osteoporosis.

In March 2024, the FDA approved the first biosimilars that reference Prolia. Developed by Sandoz, Wyost and Jubbonti are interchangeable with the reference products for all indications.

Wyost (denosumab-bbdz), a bisomilar to Xgeva, is used to prevent skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors. The FDA also approved Jubbonti (denosumab-bbdz), a biosimilar of Prolia, to treat several conditions, including men and postmenopausal women with osteoporosis.