Scientists from the U.S. Food and Drug Administration's advisory committee voted overwhelmingly to recommend approving Amgen Inc.'s osteoporosis drug Evenity despite concerns regarding cardiovascular risks found in an earlier clinical trial.
The recommendation from the Center for Drug Evaluation and Research follows on the heels of Japanese regulatory approval for the drug, which was the first and only approval so far for a class of drugs called sclerostin inhibitors. Evenity, also known as romosozumab, is a monoclonal antibody that treats osteoporosis, a low-bone-density skeletal disease that leads to bone fragility and an increased risk of fractures. The drug inhibits sclerostin, a protein thought to interfere with bone formation.
Amgen and its partner UCB SA are seeking to market the medicine in the U.S. based on evidence of its efficacy from a series of trials called FRAME, which showed no cardiovascular events. But a trial called ARCH indicated that the drug might come with such complications, and the FDA rejected Amgen's original submission on those grounds.
At the Jan. 16 meeting, scientists discussed the ARCH trial, which showed major adverse cardiovascular events in postmenopausal women in the study at 2.5%, compared to 1.9% in the patients who took the osteoporosis drug alendronate, sold by Merck & Co. Inc. under the name Fosamax.
Evenity will carry a black-box warning — the regulatory agency's highest risk alert — that cautions patients and prescribers regarding the cardiovascular risk.
The question posed to the Bone, Reproductive and Urologic Drugs Advisory Committee was whether Evenity provided enough benefit to osteoporosis patients to outweigh those potential risks.
Sixteen committee members voted "yes" to Amgen's proposed indication of the drug for postmenopausal women at high risk for bone fracture or those who are intolerant of or unable to take other drugs for the condition. Two voted for a change in the indication and one voted against the drug outright, recommending that the committee wait on future studies that would provide further insight into the risks.
Much of the discussion before the vote highlighted the difficulty of conducting trials in the osteoporosis space due to an overlap with patients at risk of adverse cardiovascular events because of age. Members of the committee still wanted to see more data from a post-market study to determine the cardiovascular risks and the populations most suited for the drug.
Committee member Frederick Kushner, who voted to approve Evenity, noted the "tremendous need for the drug" and that approval would be warranted so long as the black-box warning remains in place and the post-approval study is conducted.