Amgen gets first OK for Evenity in Japan as FDA panel looms

Jefferies is betting on U.S. approval and sales of $500 million or more. (Amgen)

Amgen will head into its FDA advisory committee meeting for new osteoporosis drug Evenity next week comforted by a first approval for the bone-building drug in Japan.

The biotech already has the top-selling biologic for osteoporosis in Prolia (denosumab), which is expected to comfortably clear $2 billion in 2018 sales and is still growing well after several years on the market. Prolia is in its last few years of patent life, however, and Amgen would like Evenity (romosozumab) to gain traction ahead of biosimilar competition.

“The number of fractures in the community of postmenopausal women is still far too high,” said Amgen CEO Rob Bradway when announcing the approval during the company’s presentation at the J.P. Morgan Healthcare conference in San Francisco yesterday. “We’re just scratching the surface of the number of patients who need to be treated to be protected against fractures.”

The Japanese approval—without any major restrictions—bodes well for the anti-sclerostin antibody’s chances of getting through the FDA panel on Jan. 16, say analysts at Jefferies. It’s important because the drug has been linked to cardiovascular safety issues that prompted the FDA to reject Amgen’s initial marketing application in 2017.

The FDA’s new position on Evenity will be much clearer when briefing documents are published ahead of the advisory committee meeting early next week, but Jefferies is hopeful of a positive outcome and reckons sales could reach $500 million or more worldwide.

That forecast is reasonable “because efficacy is very strong … and the safety signal may be more spurious than concerning,” they write in a research note.

Evenity trounced Merck’s nonbiologic osteoporosis rival Fosamax (alendronate) in head-to-head trials, cutting vertebral fractures by around 50% versus the comparator, but showed a higher rate of major cardiovascular events (MACE). The readout prompted several analysts including Evercore ISI’s Umer Raffat to take romosozumab out of Amgen sales forecasts completely, particularly as restricting the drug’s use to low-risk patients could decimate its target population given that osteoporosis generally affects elderly women.

Jefferies is now more optimistic, pointing out that the MACE imbalance was only seen in the smaller of two phase 3 trials of romosozumab. They are now predicting FDA approval with a warning on the label or a REMS plan to manage side effects, but say this is “still an attractive opportunity given high efficacy and large market.”

That’s not to say the adcomm won’t potentially throw up some problems. One issue that could scupper Amgen’s plans is the theoretical concern that sclerostin inhibition is intrinsically associated with cardiovascular risk as sclerostin is expressed in the heart, although Jefferies thinks the data on this is fairly limited.

On the other hand, it is possible that Fosamax reduces cardiovascular risk so the phase 3 MACE imbalance may have stemmed from a protective benefit in patients taking Merck’s drug.

Amgen and UCB are co-developing Evenity worldwide, with development in Japan being led by a joint venture between Amgen and Astellas. The drug is also under regulatory review in Europe.