FDA Rejects Romosozumab for Osteoporosis, Wants More Data

July 17, 2017

The US Food and Drug Administration (FDA) has rejected the osteoporosis drug romosozumab (Amgen/UCB Pharma), a decision that was widely expected when the companies reported a higher rate of serious adverse cardiovascular events with the drug compared with the bisphosphonate alendronate in the ARCH study in May.

According to a statement issued by Amgen and UCB Pharma yesterday, the FDA now wants to see data from the ARCH study as well as from BRIDGE, a trial of romosozumab in men with osteoporosis.

The agency had already been considering data from the phase 3 FRAME study with romosozumab. In FRAME, reported at the American Society of Bone and Mineral Research 2016 Annual Meeting and simultaneously published online in the New England Journal of Medicine, romosozumab reduced the rate of vertebral fractures by 73% compared with placebo. The data were called "unprecedented" by the lead investigator. However, romosozumab did not significantly reduce the risk of nonvertebral fractures, a key secondary end point of FRAME.

Romosozumab is an investigational humanized monoclonal antibody that inhibits sclerosin, giving it a unique mechanism of action among osteoporosis agents. It rapidly increases bone formation and reduces bone resorption simultaneously, increases bone-mineral density, and reduces the risk of fracture. If approved, it will be known by the tradename Evenity.

The agent had been set to compete with the first new osteoporosis drug in the United States for nearly 15 years, the osteoanabolic agent abaloparatide (Tymlos, Radius Health), which was approved in April as a subcutaneous injection for postmenopausal women with osteoporosis at high risk for fracture because of a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have not responded to or are intolerant to other available osteoporosis therapy.

But now, Amgen and UCB will have to go back to the drawing board. It's not clear why they didn't include data from BRIDGE, the trial in men, with the biologics license application for romosozumab, as the trial was completed more than a year ago.

In the statement issued yesterday, the companies say: "The US FDA has issued a complete response letter for the biologics license application for Evenity (romosozumab) as a treatment for postmenopausal women with osteoporosis."

"The original submission included data from the pivotal phase 3 placebo-controlled FRAME study of postmenopausal women with osteoporosis. With the availability of data from the phase 3 active-comparator ARCH study, the agency has asked that the efficacy and safety data from the study be integrated into the application. The resubmission will also include the efficacy and safety data from the BRIDGE study, the phase 3 trial evaluating Evenity in men with osteoporosis, which has also been requested. This request will be addressed in the form of a resubmission, which is an extension of the current review.”

The companies said in May that further analysis of the ARCH study data "is ongoing and will be submitted to a future medical conference and for publication."

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