Does Medicare Advantage Cover Evenity (Romosozumab)?

What is not settled here

The FDA label covers who the drug is for, how it is dosed and what risks it carries. It does not set prior authorization, step therapy, coinsurance or appeal rules. Those questions are answered by a plan's own Evidence of Coverage and its coverage criteria for romosozumab. The label facts below are the ones those criteria are likely to refer to.

What the label establishes

Evenity is indicated for osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or failure of, or intolerance to, other available osteoporosis therapy [1]. The label names postmenopausal women; it is not indicated for men or for premenopausal women [1].

The dose is 210 mg subcutaneously once a month for 12 monthly doses, given as two 105 mg injections one after the other [1]. The label says Evenity should be administered by a healthcare provider [1]. Duration is limited to 12 monthly doses because the anabolic effect wanes; the label says that if osteoporosis therapy is still warranted, an anti-resorptive agent should be considered, and without follow-on anti-resorptive therapy bone mineral density returns to about baseline within 12 months of stopping [1]. Romosozumab is a monoclonal antibody that inhibits sclerostin, increasing bone formation and, to a lesser extent, decreasing bone resorption [1].

What the boxed warning says

The boxed warning is titled Potential Risk of Myocardial Infarction, Stroke and Cardiovascular Death. It states that Evenity may increase the risk of myocardial infarction, stroke and cardiovascular death, and that it should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year [1]. The label also says to consider whether the benefits outweigh the risks in patients with other cardiovascular risk factors, and that Evenity should be discontinued if a patient has a myocardial infarction or stroke during therapy [1].

A recent heart attack or stroke is a restriction inside that boxed warning, not a contraindication. The contraindications listed in the label are hypocalcemia, which must be corrected before starting, and a history of systemic hypersensitivity to romosozumab-aqqg or any component of the product [1].

The label's boxed warning cites the alendronate-controlled trial: positively adjudicated major adverse cardiac events occurred in 2.0% (41 of 2,040) on Evenity versus 1.1% (22 of 2,014) on alendronate, hazard ratio 1.87 (95% CI 1.11 to 3.14) [1]. In the placebo-controlled trial the rates were 0.8% (30) versus 0.8% (29), hazard ratio 1.03 (95% CI 0.62 to 1.72) [1].

What the two fracture trials showed

The placebo-controlled trial enrolled 7,180 postmenopausal women with a T-score of -2.5 to -3.5 at the total hip or femoral neck, randomized to monthly romosozumab 210 mg or placebo for 12 months, then denosumab for 12 months [2]. At 12 months, new vertebral fractures occurred in 0.5% versus 1.8% (73% lower risk); clinical fractures in 1.6% versus 2.5% (36% lower, P=0.008); nonvertebral fractures in 1.6% versus 2.1% (not significant, P=0.10) [2]. At 24 months, vertebral fractures were 0.6% versus 2.5% (75% lower) [2].

The alendronate-controlled trial enrolled 4,093 postmenopausal women with osteoporosis and a fragility fracture, randomized to monthly romosozumab 210 mg or weekly alendronate 70 mg for 12 months, then open-label alendronate in both groups [3]. At 24 months, new vertebral fractures were 6.2% versus 11.9% (48% lower); clinical fractures 9.7% versus 13.0% (27% lower); nonvertebral fractures 8.7% versus 10.6% (19% lower, P=0.04); hip fractures 2.0% versus 3.2% (38% lower, P=0.02) [3].