If you thought Amgen osteoporosis candidate Evenity (romosozumab) was down for the count, think again.
After an overwhelmingly positive 18-1 vote in favor of approval from an FDA advisory panel Wednesday afternoon, the drug is “back in the game,” as Jefferies analyst Michael Yee put it in a note to clients.
Asked to vote on whether the overall risk/benefit profile of the prospect was acceptable to support its approval in postmenopausal women with osteoporosis at high risk for fracture, 16 experts voted yes; two voted yes, but with a different indication; and one voted no.
“In our view, the panel generally thought” the increased rate of cardiovascular events seen in trials “was likely to be spurious and still voted for approval,” Yee said.
That positive panel vote—coupled with “largely benign commentary” on the drug’s cardiovascular risks—was enough to convince Yee and his colleagues that there’s now “a high probability that romo will be approved.”
That’s a big shift from the way industry watchers saw things in May 2017, after Evenity turned up cardiovascular red flags in the phase 3 Arch study. The result, which was “clearly negative, and very surprising,” as Evercore ISI analyst Umer Raffat put it at the time, threw major doubt on an eventual approval, and at that point Leerink Partners’ Geoffrey Porges pegged the drug’s chances at just 50-50.
Of course, a green light still isn’t necessarily in the bag for Amgen and partner UCB; the FDA doesn’t always follow the recommendations of its panels. But heading into this one, Bernstein analyst Wimal Kapadia noted that the tone the agency took in its briefing documents was “neutral, convening genuine need for advice.”
Meanwhile, Amgen was pleased with the vote, and R&D EVP David Reese, M.D., in a statement emphasized the need for additional therapies. After an osteoporotic fracture, a woman is five times more likely to suffer another bone break within the first year, and “her risk remains elevated over time if untreated,” he said.
“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,” Reese added.
As analysts have noted, though, even if Amgen and UCB can score a go-ahead, Evenity won’t have the easiest path ahead. For one, Yee, expects it to bear a black box warning—the FDA’s most serious—that suggests doctors limit use to high-risk patients who haven’t had a heart attack or stroke within the past 12 months. Before the vote, Leerink’s Porges predicted that Evenity, if approved, would carry “a duration of treatment limitation of one year” in addition to the black box, and that its manufacturers would be “saddled with onerous postmarketing safety requirements.”
“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 wrote earlier in the week.
Yee, though, was more upbeat, predicting that even factoring in those sales limitations, Amgen could still wind up with a $500 million worldwide opportunity. Fellow osteoporosis drug Forteo from Eli Lilly has a black box warning “and did $2B,” he wrote.