FDA Accepts Sandoz Denosumab BLA for Review

The FDA accepted Sandoz’ biologics license application (BLA) for the company’s denosumab biosimilar (GP2411) referencing Prolia/Xgeva for review.

If approved, the biosimilar will be used in the treatment of premenopausal patients with osteoporosis who are at increased risk of fractures as well as patients with treatment-induced bone loss. The denosumab candidate will also be used to prevent skeletal related complications in cancer that manifests or spreads to the bone and in the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.

“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…. 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 US, while also delivering savings for healthcare systems,” commented Keren Haruvi, president and head of North America at Sandoz, in a company statement.

Denosumab products are human monoclonal antibodies that bind to RANKL proteins, an activator for osteoclasts, which break down bone tissue. By inhibiting RANKL, denosumab decreases osteoclast production and activity.

According to Sandoz, over 10 million adults over age 50 in the United States have osteoporosis, of whom most (over 80%) are women. It is predicted that 1 in 2 women and 1 in 4 men will experience an osteoporosis-related fracture in their lifetimes, which could result in decreased quality of life, disability, and death.

The BLA included data from that phase 1/3 ROSALIA clinical trial. The results demonstrated the biosimilarity between Sandoz’ denosumab and the reference product in postmenopausal women with osteoporosis in terms of pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity.

The news comes after Novartis announced spinning off Sandoz, which used to be the former’s generics and biosimilars division, into a stand-alone company in August 2022. In July 2022, the FDA accepted BLA applications for its natalizumab biosimilar referencing Tysabri and the high-concentration version of its adalimumab biosimilar (Hyrimoz) referencing Humira.

Additionally, Sandoz has developed 7 other biosimilars, including Omnitrope (somatropin), Erelzi (etanercept), Binocrit (epoetin alfa), Ziextenzo (pegfilgrastim), Rixathon (rituximab), Zessly (infliximab), and Zarzio/Zarxio (filgrastim). Zarxio was the first biosimilar to be approved in the United States and the European Union. However, because it was approved prior to the implementation of a biosimilars approval pathway, Zarxio is formally not classified as a biosimilar in the United States. Sandoz also has an aflibercept biosimilar candidate (SOK583A1) being tested in a phase 3 study.

Growing the Denosumab Pipeline

There are several other companies looking to break into the denosumab biosimilar space. AryoGen Pharmed released positive phase 3 trial results for its denosumab candidate. In July 2022, Alvotech initiated a phase 1 pharmacokinetics study for its denosumab (AVT03). JHL Biotech began a phase 1 trial for its candidate (JHL 1266).

Shanghai Henlius Biotech’s denosumab (HLX14) was assessed in a phase 3 trial that began in July 2022. The biosimilar was approved by China’s National Medical Products Administration in June 2020.

Celltrion Healthcare and Samsung Bioepis are tested their denosumab candidates and Enzene Biosciences entered into a commercialization agreement with Hetero for a denosumab biosimilar. The 2 partners received regulatory approval for its biosimilar for the Indian market in September 2021.