Updated: FDA signals likely full approval for Eisai’s new Alzheimer’s drug ahead of Friday’s adcomm

The FDA said Wednesday that the confirmatory trial that Eisai and Biogen ran to show their new Alzheimer’s drug has a clinical benefit did indeed have one, lining Leqembi up for a likely full approval next month after getting an accelerated nod in January.

Ahead of Friday’s advisory committee meeting, which features just six voting members, FDA reviewers affirmed what Eisai and Biogen said at the time about the results of the confirmatory trial, known as CLARITY AD, adding that:

Any group-level mean change from baseline on the CDR-SB [Clinical Dementia Rating-Sum of Boxes] that is reduced, to a statistically significant extent in an appropriately powered study, compared to placebo is considered clinically meaningful.

The agency also said that the positive finding on the primary endpoint is supported by statistically significant results for all four multiplicity-controlled secondary endpoints, “including clinical endpoints capturing distinct information regarding cognitive decline.”

As far as safety-related issues, which include amyloid-related imaging abnormalities (ARIA), cerebral hemorrhage, and infusion-related reactions and hypersensitivity, the FDA reviewers sounded positive again, saying the “risks do not appear to preclude traditional approval. Risk can be mitigated through a description in labeling and recommendations for monitoring and dose management guidelines as provided for in labeling.”

“We feel very comfortable about Friday,” Eisai’s US CEO Ivan Cheung told Endpoints News in a phone interview Wednesday. “We welcome any panel member asking any question.”

He said he didn’t know why there were only six voting members on the committee, adding that there’s variability in the size of the committees.

A positive vote will likely mean a swift full approval and wider coverage from both the CMS and private insurers, which until now have limited the use of Leqembi and Biogen’s Aduhelm to clinical trials despite their accelerated approvals. CMS recently said it plans to cover Leqembi if it receives full approval. The drug’s PDUFA date is July 6. Cheung said he expects CMS coverage based on the FDA’s label to begin on the day of the approval.

Ivan Cheung

“We have to sort out this coverage piece,” Cheung said. “Whatever the requirements that CMS put in place needs to be very simple with very low or minimal administrative burden on physicians and their workflows.”

The sole voting question on Friday is: “Do the results of Study 301 (CLARITY AD) verify the clinical benefit of lecanemab for the treatment of AD?”

Other experts in the field have questioned the extent to which the CLARITY results are meaningful to patients, particularly as Leqembi cannot reverse the course of Alzheimer’s.

“It’s a modest effect. They haven’t stopped progression in people that had the drug, but a 27% lowering is significant,” Robert Vassar, a longtime Alzheimer’s researcher who helped identify the beta-secretase enzyme one, BACE1, which is the precursor to amyloid beta, previously told Endpoints News.

In a statement today, Sen. Bernie Sanders (I-VT) raised issues about the price of Leqembi, which is $26,500 a year. He noted that “the Institute for Clinical and Economic Review, an independent non-profit organization, estimated in March that this drug should be sold for as little as $8,900 per year based on its effectiveness.”

“I love the senator. We respect every member of Congress,” Cheung said, but noted that the the figure cited by Sanders is on the low end of the ICER range, and that Leqembi is reasonably priced because “we do have to give discounts so when you think about the net price, we are within the ICER range.”

Eisai has said it expects Leqembi sales could top $7 billion annually by 2030. Cheung said the company has not discussed with CMS the financial impact of Leqembi on the Medicare system, premiums or deductibles. Previously, prior to the roll out of Aduhelm, CMS tweaked the premiums for seniors because of its expectations around billions in Aduhelm sales.

The accelerated approval was based on Phase II data that demonstrated Leqembi reduced the accumulation of Aβ plaque in the brain. At that time, Aβ plaque in the brain was used as a surrogate endpoint because it was thought to predict clinical benefit but is not a measure of clinical benefit.

Article updated with information from interview with Eisai US CEO Ivan Cheung.

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