FDA Approves New Alzheimer's Drug, Leqembi. Can It Escape Aduhelm's Fate?

The FDA announced today that it had pproved a new Alzheimer’s drug that seemed to be priced and approved in way to avoid the controversy and commercial failure that engulfed Aduhelm (aducanumab).

The new drug, lecanemab, which is going to be sold under the brand name Leqembi (pronounced le-KEM-bee) will be priced at $26,500 per year for the typical patient by Eisai Co., a Japanese company, and Biogen, the Cambridge, Massachusetts, company that put Aduhelm on the market.

That is higher than the price range of $8,500 to $20,600 that the Institute for Clinical and Economic Review (ICER), a well-regarded drug pricing organization, said was justified by Leqembi’s benefits in a draft report ICER issued last month. But it is far less than Aduhelm’s starting price of $56,000, which Biogen eventually cut in half.

And while FDA approved Leqembi as a treatment for Alzheimer’s, the FDA-approved label for the drug narrows the suggested use to people with mild cognitive impairment or in the early, mild dementia phase of Alzheimer’s disease. The label also says that patients should have evidence of beta amyloid pathology.

Both Aduhelm and Leqembi are monoclonal antibodies that are believed to work by reducing deposits of beta amyloid — often to referred to beta amyloid plaques — that many Alzheimer’s experts believe play a causal role in the disease.

Six million is often given as the number of people with Alzheimer’s disease the United States. But in its draft report on Leqembi and donanemab, another anti-beta amyloid drug that the FDA is likely to approve this year, ICER estimated that there are just 1.4 million people in the U.S. who would be candidates for Alzheimer’s treatments that target beta amyloid.

Leqembi won’t be easy drug to take. It is infused intravenously, so patients will have to go infusion centers. The approved dosage is two infusions each month. It may also have to be taken for quite some time before it has an effect. Some early clinical trials show no benefit after a year. The phase 2 trial on which the FDA based its approval lasted 18 months.

Payment and coverage may also loom high as hurdles for many patients. Eisai said in a news release today that “looks forward to continuing to engage constructively with various payers,” including CMS.

But in the wake of the controversy about Aduhelm and its effectiveness, CMS announced in April 2022 that it was limiting Medicare coverage of Aduhelm to people enrolled in clinical trials and that the limitation would apply to “any future monoclonal antibodies directed against amyloid approved by the FDA with an indication for use in treating Alzheimer’s disease.”

Eisai said its drug may be covered by Medicaid under a post accelerated approval process by also acknowledged that Medicaid coverage is decided state by state.

Side effects may be another impediment to the use of Leqembi. According to an FDA summary written by FDA officials, 12% (20 of 161) of the patients in the treatment arm of the phase 2 study that was submitted to drug approval agency had amyloid-related imaging abnormalities (ARIA), a side effect that result in brain swelling (edema) and small bleeds (microhemorrahges), compared with 5% (13 of 245) in the placebo group. However, just 3% (5 of 161) of the cases were symptomatic.

Results of larger, phase 3 trial of Leqembi published in yesterday’s issue of the New England Journal of Medicine showed that 17.3% of patients assigned to take Leqembi had bleeds related to ARIA compared with 9% in the placebo. But as in the phase 2 trial, most (78%) of the cases were symptomatic.

The FDA approved Leqembi under its accelerated approval process that weighs the effectiveness of drugs based on surrogate markers, which in Leqembi’s case was reduced levels of beta amyloid plaques. One of reasons Aduhelm stirred up controversy is that the approval hinged on its effects on beta amyloid, not on its benefits on cognition, memory and other aspects of thought adversely affected by Alzheimer’s.

“We remain uncertain that amyloid removal is an appropriate surrogate outcome for clinical benefit and instead look to the clinical outcomes found in randomized trials,” ICER said in its December 2022 draft report.

The results in the New England Journal of Medicine showed a 45% difference between the Leqembi group and the placebo group in a measurement of thinking used in Alzheimer’s research called the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at the end of the 18-month clinical trial.