FDA Votes in Favor of Romosozumab Approval for Osteoporosis

JANUARY 17, 2019
Krista Rossi
FDA, The US Food and Drug Administration (FDA) Bone, Reproductive, and Urologic Drugs Advisory Committee (BRUDAC) recently voted in favor of approving Amgen and UCB’s romosozumab (EVENITY) for the treatment of postmenopausal women with osteoporosis at high risk for fracture.  

Only 1 of the 19 members voted against approval, which followed a review of the safety and efficacy from the pivotal phase 3 clinical trials. In the vote, the committee also stressed the necessity of post-marketing follow-up.

"The FDA Advisory Committee's decision to recommend approval of romosozumab for treatment of postmenopausal women with osteoporosis at high risk for fracture represents a substantial advance for women with this disease and their caregivers,” Felicia Carmen, MD, to,d MD Magazine®. “Romosozumab is a very potent medication that rapidly repairs skeletal defects and restores skeletal integrity. For patients who have had recent fractures, or have had multiple risk factors for future fracture, we need more options and romosozumab is a welcome addition to our armamentarium."

Nineteen clinical trials were included in the romosozumab development program, which enrolled 14,000 patients, approximately. The primary phase 3 clinical trials included in the review were FRAME, a placebo-controlled study involving 7,180 postmenopausal women with osteoporosis at risk for fracture; ARCH, an active comparator-controlled study involving 4,093 postmenopausal women with osteoporosis and with prior history of fracture; and STRUCTURE, an active comparator-controlled study involving 436 postmenopausal women with osteoporosis.

In the phase 3 FRAME trial, 16 of 3321 patients (.5%) in the romosozumab-treated group experienced new vertebral fractures compared to 59 of 3322 (1.8%) in the placebo-treated patients. This difference demonstrated a 73% lower risk with romosozumab; P<.001. Clinical fractures occurred in 58 of 3589 romosozumab-treated patients (1.6%) compared with 90 of 3591 (2.5%) in the placebo-treated patients, showing a 36% lower risk with romosozumab; P=.008). Additionally, 56 of 3589 of the romosozumab-treated patients (1.6%) experienced nonvertebral fractures compared to 75 of 3591 (2.1%) in the placebo-treated patients (P=.10).

After each group made the transition to denosumab, the rates of vertebral fractures were significantly lower at 24 months in the romosozumab-treated patients than in the placebo-treated patients (.6% [21 of 3325 patients] in the romosozumab group vs. 2.5% [84 of 3327] in the placebo group, a 75% lower risk with romosozumab; P<.001).

Hyperostosis, cardiovascular events, osteoarthritis, and cancer included adverse events, which were balanced between the groups. Two cases of osteonecrosis of the jaw and 1 atypical femoral fracture were noted in the romosozumab group.

In July 2018, Amgen resubmitted the biologics license application to the FDA for romosozumab the treatment of osteoporosis in postmenopausal women at high risk for fracture. The resubmission included

 "A fracture due to osteoporosis can be devastating to the lives of patients,” David M. Reese, MD, executive vice president of Research and Development at Amgen said in a recent statement. “After an osteoporotic fracture, a woman is 5 times more likely to suffer another fracture within the first year, and her risk remains elevated over time if untreated. Despite available therapies, these women who are at high risk for fracture could benefit from an additional treatment option that has the potential to both build new bone and slow existing bone loss.”

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