Amgen and UCB’s osteoporosis drug Evenity has finally won over the FDA, thanks to a pared-back indication in high-risk women. But the agency didn’t pass over the safety signal that torpedoed the drug the first time around—and that could limit its uptake.
The FDA on Tuesday approved Evenity (romosozumab) to treat osteoporosis in post-menopausal women at high risk of fracture, a smaller group of women than Amgen targeted in its first application. And the agency narrowed that target further, barring women who have suffered a heart attack or stroke within the previous year.
That restriction, featured in a boxed warning, stems from an increased risk of cardiovascular (CV) problems spotted in a phase 3 trial, the very study that prompted an FDA rebuff in 2017. Amgen will also be on the hook for a required postmarketing study focused on CV safety.
The company said it won't reveal Evenity's sticker price until the drug launches, probably next week.
Despite the warning, and the fact that the approval doesn't cover all menopausal women, Jefferies analyst Michael Yee figures there’s still a sizable market that could net Amgen over $500 million in peak worldwide sales.
Evenity increases bone growth by inhibiting the activity of sclerostin, a protein that regulates bone formation. Widely used bisphosphonate drugs and Amgen's very own antibody drug Prolia for osteoporosis prevent the loss of bone mass but don’t stimulate bone growth, and therefore don’t correct structural damage.
Evenity proved itself in two phase 3 studies, one of them a head-to-head against Merck & Co.'s bisphosphonate med Fosamax. In the 7,180-patient Frame study, the Amgen drug cut the risk of new spine fractures compared to placebo. And in the Arch study, which enrolled some 4,900 postmenopausal women with a high risk of fracture, Evenity topped Fosamax at reducing the incidence of new fractures in the spine and in other bones, and at increasing bone mineral density.
But it was the Arch study that raised red flags about Evenity's CV safety. A slight imbalance in CV adverse events cropped up in the study; 50 patients (2.5%) in the Evenity arm and 38 patients (1.9%) in the Fosamax arm developed CV symptoms. Even though the risk didn’t show up in the larger Frame study, the Arch data were enough to cost Evenity a 2017 nod.
Amgen and UCB then refiled and sought approval only in women at high risk of fracture. In January, an FDA advisory panel voted 18-1 in favor of Evenity in that indication. The FDA followed the panel's advice by requiring a five-year observational study—potentially followed by a comparative safety study—to assess the drug’s CV profile.
Evenity will compete against Eli Lilly’s Forteo and Radius Health’s Tymlos, both of which are considered bone anabolic agents that boost bone formation.
Is the boxed warning an obvious caveat limiting Evenity's reach? Yes. But Jefferies’ Yee, in a Tuesday memo to investors, noted that Forteo—approved for both men and women—raked in $1.5 billion in 2018 sales despite a boxed warning that highlights the risk of bone cancer.
Tymlos, though, has been off to a slow start, reaching only $34.4 million in the fourth quarter of 2018. But things seem to be on the mend for Tymlos, as Radius reported it had captured over 40% of new anabolic patient starts and 29% of the overall U.S. anabolic market in the first six weeks of 2019.
Forteo goes off patent this year, and Pfenex has already submitted a new drug application for PF708, a potential copycat. Lower-priced knockoffs could put some pressure on both Tymlos and Evenity going forward.
Evenity is given as a monthly treatment for a year. Tymlos and Forteo, in contrast, are both daily injections. Because its bone-forming benefit wanes after 12 doses, Evenity shouldn’t be used beyond that point. Patients should instead switch to the old-school osteoporosis treatments that reduce bone breakdown, according to the FDA.
Editor's Note: A previous version of the story misidentified Amgen’s Prolia as a bisphosphonate. It is a monoclonal antibody.