Amgen osteoporosis candidate Evenity (romosozumab) is trying to score an approval after cardiovascular red flags derailed it in mid-2017. But analysts aren’t so optimistic.
The drug is slated to go before an FDA panel of experts later this week, but briefing documents from the FDA suggest that “risk for approval remains high and even if approved, usage would probably not be high enough” to make a significant sales impact for Amgen or partner UCB, Bernstein analyst Wimal Kapadia wrote in a note to clients.
The reason? In light of the CV risk turned up in an earlier trial, Amgen is going for a narrower indication this time; it's asking the FDA for a green light to treat osteoporosis only in postmenopausal women at high risk of fracture, rather than all postmenopausal women, the FDA said.
But "what we do not see in this document is any 'breaking of the compromise'—a subpopulation or test that would allow Evenity to be used with lower risk” than the drug posted in the phase 3 Arch trial that initially did it in, Kapadia wrote—or, in the words of Evercore ISI’s Umer Raffat, the trial that “ruined everything.”
Indeed, the FDA plans to ask its advisers to “discuss whether the benefit/risk profile of romosozumab could be improved by further narrowing the indicated population to patients at low cardiovascular risk, and if so, how to define the narrowed population.”
Outside of the Arch study, Evenity hasn’t shown any cardiovascular warning signs. In a larger phase 3 trial, dubbed Frame, “there was no imbalance on CV events at all. Yes, one phase 3 had an imbalance and other didn’t,” Raffat pointed out. That fact has helped Evenity claw its way into an appearance before the FDA advisory committee, as well as a recent approval in Japan.
Even if the drug can snag an FDA nod, Bernstein’s analysts expect to see a CV safety trial requirement. And beyond that, “it is tough for us to see practicing physicians giving patients a drug that helps 4% of the time, but could lead to CV events 0.4% of the time,” Kapadia noted.
Meanwhile, if Evenity does reach the market, it’ll have to go up against Radius’ Tymlos, a 2017 approval that lucked out when Amgen and UCB hit their hurdle. The company is “very, very pleased” with the drug’s performance so far, Radius CEO Jesper Høiland said in a recent interview.