FDA Accepts Application for Osteoporosis Drug Romosozumab

Approval decision scheduled for July

The FDA has accepted for review the biologics license application (BLA) for romosozumab (Amgen/UCB), an investigational monoclonal antibody for the treatment of osteoporosis in postmenopausal women at increased risk of fracture. Romosozumab works by binding and inhibiting the activity of sclerostin, a protein present in bone, thereby increasing bone formation and decreasing bone resorption.

The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of July 19, 2017.

Romosozumab is an investigational bone-forming monoclonal agent and is not currently approved by any regulatory authority for the treatment of osteoporosis. It is designed to work by inhibiting the activity of the protein sclerostin, and has a dual effect on bone, both increasing bone formation and decreasing bone breakdown. Romosozumab is being studied for its potential to reduce the risk of fractures in a global phase 3 program. This program includes two large fracture trials that are comparing romosozumab with either placebo or an active comparator in more than 10,000 postmenopausal women with osteoporosis. Amgen and UCB are codeveloping romosozumab.

The BLA for romosozumab, submitted on July 19, was based on data from the pivotal phase 3, randomized, double-blind, placebo-controlled, parallel-group FRActure Study in Postmenopausal WoMen With OstEoporosis (FRAME), which enrolled a total of 7,182 patients with osteoporosis (defined as low bone mineral density at the total hip or femoral neck). The patients were randomly assigned to receive either subcutaneous (SC) romosozumab (210 mg) or placebo once monthly for a 12-month double-blind study period. This placebo-controlled phase was followed by an open-label phase in which all of the patients received SC denosumab (60 mg) every six months for 12 months while remaining blinded to the initial treatment. An additional 12-month extension period of open-label SC denosumab (60 mg), administered every six months, is currently ongoing.

The study evaluated the efficacy of romosozumab, compared with that of placebo, in reducing the risk of new vertebral fractures during 12 months of therapy. The study also investigated whether 12 months of treatment with romosozumab followed by 12 months of denosumab, compared with placebo followed by denosumab, was effective in reducing the risk of new vertebral fractures through 24 months of treatment. In addition, clinical fracture (a composite endpoint that encompasses all symptomatic fractures, both nonvertebral and painful vertebral fractures) risk reduction, nonvertebral fracture (i.e., fractures outside of the spine, excluding sites that are not considered osteoporotic, fractures due to high trauma, or pathologic fractures) risk reduction, and other endpoints were assessed at 12 and 24 months.

Source: Amgen; September 26, 2017.