The European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) announced it has adopted a negative opinion of EVENITY (romosozumab-aqqg), an osteoporosis drug for postmenopausal women with high fracture risk.
The U.S. Food and Drug Administration (FDA) approved the drug, manufactured by Amgen in partnership with UCB, in April, but the approval came with a boxed warning for possible increased risk of heart attack, stroke, and cardiovascular death. The FDA also noted, “Health care professionals should also consider whether the benefits of Evenity outweigh its risks in those with other risk factors for heart disease and should discontinue Evenity in any patient who experiences a heart attack or stroke during treatment.”
In a release, the EMA said the cardiovascular risk was its primary concern.
“As it was unclear why the medicine appeared to increase the risk of heart and circulatory problems, and there was no obvious group of patients in whom the risk of these was lower, measures to reduce the risk could not readily be put in place,” the EMA stated, adding that while the drug effectively reduced fracture risk in patients with severe disease, it was not as beneficial in patients with more mild osteoporosis.
“Under the circumstances, the Agency’s opinion was that the benefits of Evenity did not outweigh its risks and it recommended refusing marketing authorization,” according to the EMA.
UCB, which filed the request, can apply for a request for re-examination by the CHMP within 15 days of the opinion being issued, which Amgen said in a press release it intends to do.
David M. Reese, MD, executive vice president of Research and Development, Amgen, said in a statement that the company is “disappointed” by the opinion and stands by the belief that “EVENITY has a positive benefit:risk profile.”
Dr. Pascale Richetta, head of bone and executive vice president, UCB, similarly expressed disappointment and added, “Together with Amgen we will seek a re-examination of the CHMP opinion. The re-examination process gives us the opportunity to clarify our position on the submitted data with the goal of making EVENITY available to postmenopausal women at high risk of fracture in the EU.”
Romosozumab-aqqg was tested in two clinical trials that included a total of more than 11,000 women with postmenopausal osteoporosis. The first trial compared one-year efficacy of romosozumab-aqqg to placebo and found that it reduced the risk of new vertebral fracture by 73% compared to placebo; this continued over the second year as well when the medication was followed by a year of denosumab—another osteoporosis therapy—compared to placebo followed by denosumab. The second trial compared romosozumab-aqqg to alendronate—another osteoporosis therapy—and found that one year of romosozumab-aqqg reduced new vertebral fracture risk by 50% compared to two years of alendronate. It was in this trial—not the placebo trial—where an increased risk was observed for cardiovascular death, heart attack, and stroke. Romosozumab-aqqg is therefore not indicated for patients who have had a heart attack or stroke within the previous year.