FDA panel gives unanimous support to Leqembi

Brain scan CNS

The first full regulatory approval for an amyloid-targeting therapy for Alzheimer’s disease could come within a month, after an expert panel voted 6 to 0 in favour of Eisai and Biogen’s Leqembi.

The Peripheral and Central Nervous System Drugs advisory committee agreed with the FDA’s own assessment that the results of the CLARITY-AD study confirmed that Leqembi (lecanemab) conferred a clinically meaningful benefit to Alzheimer’s patients.

In the phase 3 trial, Leqembi was shown to slow cognitive decline in early Alzheimer’s patients - measured using the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale at 18 months of treatment - by 27% compared to placebo.

The panel also found that the risk-to-benefit profile for the drug was acceptable in various patient subgroups, including patients with two copies of apolipoprotein E (ApoE) ε4 gene, on anticoagulants or with cerebral amyloid angiopathy, who seem to be at elevated risk of side effects, and particularly potentially life-threatening amyloid-related imaging abnormalities (ARIA).

Overall, the rate of ARIA with oedema (ARIA-E) was 13% among Leqembi-treated patients in CLARITY-AD, with 17% of patients experiencing ARIA with haemorrhage (ARIA-H), but tended to occur early on in treatment, according to data presented at the meeting.

On balance, the panel concluded that monitoring of patients in the early months of treatment would minimise the risk, even for the higher-risk groups, and it was outweighed by the drug’s benefits.

The FDA does not have to follow the committee’s recommendation, but often does, and there’s now broad expectation that the agency will convert the accelerated approval for Leqembi granted in January into a full approval, which should unlock the commercial market for the drug.

If it is forthcoming, the Centres for Medicare and Medicaid Services (CMS) has said it will provide broader coverage – meaning Medicare patients could get access to Leqembi – as long as they agree to participate in a registry to allow their real-world experience with the drug to be monitored and recorded over time via a CMS-operated portal.

The news was received with jubilation by the Alzheimer’s Association's chief executive, Joanne Pike, who said “we are now one step closer to more people living with Alzheimer’s having more time with more of their capabilities intact – to do the things they want to do and love to do best.”

The patient organisation was among groups that submitted comments urging the advisory committee to recommend full approval of Leqembi.

“We are in full agreement with the FDA Advisory Committee that Leqembi provides clinical benefit and that this benefit outweighs the risks,” said Pike. “Now, all eyes turn to CMS. Medicare is supposed to be a rock-solid guarantee for Americans, and it is time for CMS to step up and provide Medicare access on the day of an FDA traditional approval.”

Leqembi is currently being sold at a list price of $26,500, and Eisai has said it is forecasting more than $7 billion in Leqembi sales by 2030, assuming regulatory approvals in the US and other markets follow its expected timeline.

Drug cost-effectiveness organisation ICER said recently, however, that a fair price for the amyloid-busting drug would be between $8,900 and $21,500 per year, well below Eisai’s current price.