FDA committee supports Leqembi for early Alzheimer’s treatment
Panel's unanimous recommendation comes before final decision expected in July
A U.S. Food and Drug Administration (FDA) advisory committee has decided that data from the Phase 3 Clarity AD trial are sufficient to confirm the clinical benefits of Leqembi (lecanemab) for the treatment of early Alzheimer’s disease.
The FDA now will consider the unanimous opinion of the committee when deciding whether Leqembi should receive full (traditional) approval for the treatment of early Alzheimer’s, an indication for which it earned conditional approval in January.
A supplemental biologics license application seeking to transition Leqembi to a full approval is currently under priority review with the FDA, backed by data from the global confirmatory Phase 3 CLARITY AD trial (NCT03887455).
A final decision from the FDA is expected by July 6. According to a recent press release from Eisai and Biogen, Leqembi also is being considered for potential approvals in the U.K., Canada, Japan, China, South Korea, and the European Union.
The FDA granted Leqembi accelerated approval earlier this year, which allowed the companies to conditionally market the therapy based on early evidence that it is likely to be effective, but with the requirement that additional clinical studies need to confirm its efficacy.
That decision was informed by data from the Phase 2b Study 201 trial (NCT01767311), which found that twice monthly into-the-vein infusions of Leqembi reduced amyloid-beta accumulation and slowed cognitive declines.
At the time of Leqembi’s conditional approval, the Phase 3 CLARITY trial — whose data are now supporting Eisai’s application to convert Leqembi to a full approval — was already underway.
Clinical trial design
A total of 1,795 people with early Alzheimer’s, defined as mild cognitive impairment due to disease or mild Alzheimer’s dementia, were enrolled in the trial and assigned randomly to receive Leqembi or a placebo once every two weeks for 18 months (1.5 years).
Data showed that the rate of cognitive and functional decline, as assessed by the Clinical Dementia Rating-Sum of Boxes, was significantly slower — by about 27% — with Leqembi compared with placebo after 18 months, meeting the trial’s main goal.
Secondary trial outcomes also favored Leqembi, including other measures of cognitive function, patients’ ability to participate in daily activities, and measures of amyloid aggregates in the brain.
Common side effects in the Leqembi group included infusion-related reactions (26.4%), headache (11.1%), and fall (10.4%).
Amyloid-related imaging abnormalities (ARIA), a family of side effects known to be associated with anti-amyloid therapies, also were more commonly observed in the Leqembi group than with a placebo. Specifically, brain bleeds (ARIA-H) occurred in 17.3% of patients in the Leqembi group and brain swelling (ARIA-E) occurred in 12.6%.
The purpose of an FDA advisory committee meeting is for independent experts to convene and discuss the benefits and risks of a therapy for a certain patient group. The opinion of those experts is used to inform the FDA, but the agency’s decision does not necessarily have to align with the committee’s vote.
Now, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee has voted 6-0 that these data from Clarity AD support the clinical benefit of Leqembi for Alzheimer’s, and that the therapy has a favorable benefit-to-risk profile.
The committee also discussed the use of Leqembi for certain patient subgroups that may be at a higher risk for side effects, including those with the apolipoprotein E-E4 genetic risk variant, patients requiring blood thinners, and those with cerebral amyloid angiopathy, in which amyloid buildup affects blood vessels in the brain.
Long-term extension study
As the FDA’s upcoming decision is awaited, participants from CLARITY AD are continuing to be treated with into-the-vein Leqembi in a long-term extension study.
About 40 patients who did not participate in the main trial also are included and are receiving an under-the-skin (subcutaneous) formulation of the therapy, for which Eisai plans to seek approval by the end of its fiscal year.
Another Phase 3 trial called AHEAD 3-45 (NCT04468659) is evaluating Leqembi in adults with preclinical Alzheimer’s disease, or those who have elevated brain amyloid but don’t have symptoms of the disease. It is recruiting up to 1,400 patients at more than 100 locations globally.