FDA Accepts BLA for Denosumab Biosimilar for Reference Product Indications


The FDA has accepted for review a biologics license application for a proposed denosumab biosimilar, according to an announcement from Sandoz, Inc.



The FDA has accepted for review a biologics license application (BLA) for a proposed denosumab biosimilar, according to an announcement from Sandoz, Inc.1

The application includes all indications for the reference products for denosumab (Prolia; Xgeva), including 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 BLA includes a thorough package of analytical and clinical data, including findings from the phase 1/3 ROSALIA study (NCT03974100). Results showed that the proposed biosimilar denosumab demonstrated comparable pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity to the reference medicine in postmenopausal women with osteoporosis, and 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 US 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 US, while also delivering savings for health-care systems.”

In the US alone, over 10 million adults over the age of 50 are estimated to have osteoporosis, the majority of which are women. Approximately half of these women and one in four men will have an osteoporosis-related fracture in their lifetimes, which may result in reduced quality of life, disability, and even death.

Denosumab is a human monoclonal antibody designed to bind to the RANKL protein, an activator of osteoclasts or cells involved in breaking down bone tissue. By inhibiting RANKL, denosumab reduces the activity of osteoclasts, leading to less bone loss, fractures, and other serious bone conditions.

On September 19, 2022, Sandoz announced that the ROSALIA trial met its primary end points.2

In ROSALIA, 527 postmenopausal women with osteoporosis were randomly assigned to receive the biosimilar for denosumab or the reference product for up to 78 weeks of treatment.

The aim of the study was to demonstrate similar efficacy in terms of change in lumbar spine bone mineral density, as well as similar pharmacokinetics and pharmacodynamics.


  1. Sandoz biologics license application for proposed biosimilar denosumab accepted by US FDA. News release. Sandoz. February 6, 2023. Accessed February 6, 2023. https://www.novartis.com/news/media-releases/sandoz-biologics-license-application-proposed-biosimilar-denosumab-accepted-us-fda
  2. Sandoz announces further progress on its biosimilar pipeline, with release of positive results for denosumab integrated phase I/III clinical trial. News release. Sandoz. September 19, 2022. Accessed February 6, 2023. https://www.sandoz.com/news/media-releases/sandoz-announces-further-progress-its-biosimilar-pipeline-release-positive-results-denosumab-integrated-phase-iiii-clinical-trial
Related Videos
Christina L. Roland, MD, MS, FACS
Meredith McKean, MD, MPH
Damon R. Reed, MD
Brian A. Van Tine, MD, PhD
Breelyn A. Wilky, MD
Damon R. Reed, MD
R. Lor Randall, MD, FACS
Brian A. Van Tine, MD, PhD
Bernd Kasper, MD, PhD