April 09, 2019
3 min read

FDA approves romosozumab for osteoporosis

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The FDA on Tuesday approved the monoclonal antibody romosozumab to treat osteoporosis in postmenopausal women at high risk for fracture, according to a press release from the agency.

The approval of romosozumab (Evenity, Amgen) is indicated for women with a history of osteoporotic fracture or multiple risk factors for fracture, or those who cannot take other osteoporosis therapies or for whom other osteoporosis therapies have failed. The approval includes a boxed warning on its labeling stating that it may increase risks for myocardial infarction, stroke and CV death and should not be taken by patients who experienced a CV event within the previous year.

“Today’s approval provides women with postmenopausal osteoporosis who are at high risk of fracture with a new treatment that will reduce this risk,” Hylton V. Joffe, MD, MMSc, director of the Center for Drug Evaluation and Research’s Division of Bone, Reproductive and Urologic Products, said in the release. “Evenity may increase the risk of heart attack, stroke and cardiovascular death, so it’s important to carefully select patients for this therapy, which includes avoiding use in patients who have had a heart attack or stroke within the previous year.”

Romosozumab works by binding and inhibiting the activity of the protein sclerostin and, as a result, has a dual effect on bone, both increasing bone formation and decreasing bone breakdown. One dose of romosozumab consists of two injections, one immediately following the other, given once a month by a health care professional. The bone forming effect of romosozumab wanes after 12 doses, so more than 12 doses should not be used. If osteoporosis therapy is needed after the 12 doses, patients should begin an osteoporosis treatment that reduces bone breakdown, according to the FDA.

The safety and efficacy of romosozumab were demonstrated in two clinical trials involving a total of more than 11,000 women with postmenopausal osteoporosis. In the first trial, 1 year of treatment with romosozumab lowered the risk for new vertebral fracture by 73% compared with placebo. This benefit was maintained over the second year of the trial when romosozumab was followed by 1 year of denosumab (Prolia, Amgen) compared with placebo followed by denosumab. In the second trial, 1 year of treatment with romosozumab followed by 1 year of alendronate reduced the risk for a new vertebral fracture by 50% compared to 2 years of alendronate alone. Romosozumab followed by alendronate also reduced the risk for nonvertebral fractures compared with alendronate alone.


As Endocrine Today previously reported, the Bone, Reproductive and Urologic Drugs Advisory Committee of the FDA voted 18-1 in January in favor of recommending approval of a biologics license application for romosozumab for the treatment of osteoporosis in postmenopausal women at high risk for fracture, with two of 18 “yes” votes supporting a different indication for the drug.

In committee discussions both before and after the vote, panel members unanimously called for additional data regarding the CV safety of romosozumab, with most members supporting either a randomized controlled trial or an observational study conducted after approval. The FDA issued a complete response letter for romosozumab in July 2017, asking Amgen to add safety and efficacy data from the ARCH and BRIDGE trials into the drug application. The original application, submitted to the FDA in September 2016, was based on efficacy and safety data from the FRAME study, which did not show an increase in CV risk. Amgen and UCB resubmitted their application to the FDA in July, this time proposing to narrow the indication to treatment of osteoporosis in postmenopausal women at high risk for fracture.

“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,” the FDA stated in the release.

Common side effects of Evenity included joint pain and headache. Injection site reactions were also observed. – by Regina Schaffer

Disclosures: Joffe is director of the Center for Drug Evaluation and Research’s Division of Bone, Reproductive and Urologic Products.