Amgen, UCB refile for romosozumab approval 1 year after safety scare sunk submission

Amgen and UCB have re-filed for FDA approval of osteoporosis drug romosozumab one year after the agency rejected a submission on safety grounds. The revised filing pools all the phase 3 data in a bid to show the sclerostin-targeting antibody has a positive risk-benefit profile.

Romosozumab looked well set to come to market when it aced its first phase 3 in September 2016. That changed in May 2017 when a second phase 3 detected a new cardiovascular safety signal. Two months later, the FDA rejected a filing for approval of romosozumab in postmenopausal women with osteoporosis.

Now, Amgen and UCB have gone back to the FDA. The new filing features data from the original,  7,180-person person phase 3 trial that formed the backbone of the original submission, plus results from two other studies.

One of the other studies is the second phase 3 of romosozumab in 4,093 postmenopausal women with osteoporosis who experienced a fracture. That clinical trial found romosozumab was better than alendronate at reducing fractures but also uncovered the safety signal. The third set of data included in the filing comes from a 245 person study of the effect of romosozumab in men.

Amgen and UCB are hoping that when the FDA gets to analyze all the safety and efficacy data it will conclude the benefits of romosozumab outweigh the risks. However, there remains a chance the FDA will turn the drug down or impose a restrictive label that limits its commercial prospects.

A restrictive label could see romosozumab struggle to live up to the blockbuster forecasts made by analysts prior to the safety scare. If romosozumab comes to market, it will face competition from Eli Lilly’s Forteo and Radius Health’s Tymlos. Romosozumab has some advantages over the competition, such as monthly dosing, but these could be swept away by cardiovascular safety concerns.