Looks like Amgen and UCB’s osteoporosis drug is headed to the finish line, after an FDA panel largely supported its approval on Wednesday. But if approved, it will likely carry a black box warning advising against its use in patients with high cardiovascular risk.
The recommendation follows a rosy review from FDA staff posted on Monday, who underscored romosozumab’s efficacy in postmenopausal women with a high risk of fracture had been established, and suggested that the CV signal observed in some trials may not be a significant worry. An independent panel of experts whose recommendations the FDA typically follows endorsed the drug, in light of its efficacy in patients that usually have few treatment options, but suggested the CV risk be characterized post approval.
Overall, panel members voted 18-1 in favor of approval. The single “no” vote came from a patient representative, who thought the drug was efficacious but wanted CV risk to be determined prior to approval.
Romosozumab — which is to be sold under the brand name Evenity — functions predominantly as a bone anabolic agent that stimulates bone growth. Panel discussions suggested the drug, which is already approved in Japan and is under review in Europe, will need to feature a black box warning describing the increase in CV events observed, and the company will likely have to conduct a post-marketing study to characterize the cardio risk of the drug in the United States. Patients with high osteoporotic risk tend to be older, and hence may also be at higher risk for cardio events, various panelists acknowledged.
“In our view, the panel generally thought the increased CV event rate was likely to be spurious and still voted for approval; our base case is FDA approval in H1:19 with a blackbox that suggests use mostly in patients with high-risk osteoporosis who have not had a MI/stroke within the past 12 months,” Jefferies’ Michael Yee wrote in a note, adding that Lilly’s osteoporosis drug Forteo carries a black box warning highlighting the risk of cancer and still rakes in about $2 billion.
In the US, one in two women over the age of 50 will experience an osteoporotic fracture — an incidence that surpasses that of heart attack, stroke and breast cancer combined, according to the National Osteoporosis Foundation, which estimates osteoporosis will be responsible for three million fractures resulting in $25.3 billion in costs by 2025.
“Even when limiting use (of the drug) more broadly because of theoretical CV risk,” romosozumab represents a more than $500 million worldwide opportunity, Yee said.
Romosozumab was tested in three late-stage studies: the 7,180-patient placebo-controlled FRAME study in postmenopausal women with osteoporosis,; the 4,093-patient ARCH study in postmenopausal women in osteoporosis, which tested the drug against an osteoporosis drug originally made by Merck called alendronate; and the 245-patient placebo-controlled BRIDGE study in men with osteoporosis.
All three pivotal studies showed the monoclonal antibody was effective, but serious CV adverse events were observed the ARCH and BRIDGE trial, which prompted the FDA to issue a complete response letter to deny the approval of romosozumab in postmenopausal women with osteoporosis. Taking into account the CV signal and feedback from the FDA about the paucity of anabolic agents, the duo re-submitted an application to market drug last year, but for a narrower patient population: postmenopausal women with osteoporosis who carry a high risk of fracture, or patients who have failed or are intolerant to existing osteoporosis therapies.
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