FDA Accepts Amneal’s BLA for Two Denosumab Biosimilars

The FDA has accepted Amneal’s biologics licensing application (BLA) submission for two proposed denosumab biosimilars referencing Prolia and Xgeva with a target action date in the fourth quarter of 2025, according to a news release.

Under the agreement, mAbxience will manufacture the drugs and Amneal will have exclusive commercialization rights in the United States and pursue regulatory approval.

Denosumab is a monoclonal antibody that slows bone resorption, which is the process by which bone tissue is broken down and released into the bloodstream. When this happens excessively, it can lead to complications such as osteoporosis and bone fractures. Osteoporosis is a natural part of aging for many women who have gone through menopause, but certain cancer treatments can also weaken bone structure.

There are currently three Prolia biosimilars and three Xgeva biosimilars, including Monday's approval. The three Prolia biosimilars are Ospomyv, Stoboclo and Jubbonti and the three Xgeva biosimilars are Xbryk, Osenvelt and Wyost.

Prolia was the first approved in June 2010 for men and women with osteoporosis. Xgeva was approved in November 2010.

Although the active drug ingredient in Prolia and Xgeva is deosumab, they have different indications. Prolia is indicated for male and female patients with osteoporosis or decreased bone density due to prostate or breast cancer treatments. Xgeva is used to prevent skeletal related events, which are complications that can arise when cancer spreads to the bones, potentially leading to fractures or spinal compression.

Both Prolia and Xgeva can cause serious adverse reactions. The most common reported by patients on Prolia include back pain, arthralgia and nasopharyngitis. Patients with advanced kidney disease who take Prolia are at an increased risk for severe hypocalcemia. The most common reactions reported by patients taking Xgeva were fatigue, nausea and hypophosphatemia. Osenvelt is not recommended for pregnant women due to the risk of fetal harm. Osenvelt also carries a risk of osteonecrosis of the jaw.

The annual U.S. sales for Prolia and Xgeva totaled approximately $5 billion, according to the release.

“Amneal is building its position in the U.S. biosimilars market as this next wave of affordable medicines increases access for patients to biologics,” Chirag and Chintu Patel, co-CEOs of Amneal said in the news release. “Building on our first three successful biosimilar launches, we look to expand our portfolio next with denosumab, which is an important therapy across multiple indications, including oncology.”