Leqembi, 1st therapy to slow Alzheimer’s, wins full FDA approval

Treatment won conditional OK in January for its ability to clear amyloid beta protein

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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The U.S. Food and Drug Administration (FDA) has granted full approval to Eisai and Biogen’s Leqembi (lecanemab), the first treatment shown to slow disease progression in adults with early Alzheimer’s disease.

Leqembi won accelerated (conditional) approval in January based on Phase 2 trial data that showed it could clear the toxic plaques of amyloid beta protein from the brain. These plaques are a key feature and driver of the disease, so this was thought to predict clinical benefit.

The full approval upgrade was based on data from a Phase 3 trial that showed Leqembi was superior to a placebo at slowing cognitive and functional decline, confirming the benefit.

“Today’s action is the first verification that a drug targeting the underlying disease process of Alzheimer’s disease has shown clinical benefit in this devastating disease,” Teresa Buracchio, acting director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in an agency press release. “This confirmatory study verified that it is a safe and effective treatment for patients with Alzheimer’s disease.”

The FDA’s decision comes less than a month after all six advisers of an FDA committee voted to recommend Leqembi’s full approval on the basis of the Phase 3 results.

It makes “Leqembi the first and only approved anti-amyloid Alzheimer’s disease treatment shown to reduce the rate of disease progression and to slow cognitive impairment in the early and mild dementia stages of the disease,” Haruo Naito, Eisai’s CEO, said in a joint company press release.

Christopher A. Viehbacher, Biogen’s president and CEO, called the approval a “breakthrough” in the treatment of “a disease that was previously considered untreatable.” “Our focus is now on the path forward, working alongside Eisai with the goal of making Leqembi accessible to eligible patients as soon as possible.”

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The road to Leqembi’s full approval and what’s next

Given directly into the bloodstream, Leqembi is an antibody that targets the most neurotoxic form of amyloid beta. It’s indicated for use in people who have mild cognitive impairment or are at an early stage of Alzheimer’s and have documented evidence of amyloid beta buildup in the brain before starting treatment.

Its full approval paves the way for broader Medicare coverage, as the Centers for Medicare & Medicaid Services (CMS) had previously limited coverage of Leqembi and similar therapies to clinical trials.

Now, to receive Medicare coverage for Leqembi, doctors of eligible patients must fill out a form to take part in a CMS-qualifying real-life study, like a large patient registry.

“With FDA’s decision, CMS will cover this medication broadly while continuing to gather data that will help us understand how the drug works,” the CMS explained.

The therapy is available in the U.S. through the specialty pharmacy Soleo Health. Patients prescribed Leqembi can receive it in their homes or one of Soleo Health’s more than 35 ambulatory infusion centers.

“We are already administering Leqembi to patients nationwide and have received significant interest from many more as well as the Alzheimer’s community,” Drew Walk, Soleo Health’s CEO, said in a separate press release. “We expect interest to dramatically increase with the full FDA approval and have scaled our national clinical network and operations to meet impending demand.”

The conditional approval was mainly based on data from a Phase 2b clinical trial, called Study 201 (NCT01767311), where Leqembi, given twice a month over 1.5 years, was shown to clear toxic amyloid plaques and slow cognitive decline compared with a placebo. The study included 856 people with early Alzheimer’s.

The larger Phase 3 Clarity AD trial (NCT03887455) tested Leqembi against a placebo in 1,795 people with early Alzheimer’s. Data from 1.5 years of treatment showed the study met its main and key secondary goals, confirming Leqembi’s clinical benefit.

Particularly, it was associated with a 27% slower cognitive and functional decline and a 37% slower decline in the ability to do activities of daily living such as eating, dressing, or socializing, over a placebo.

Side effects of Leqembi

Common side effects include infusion reactions, headaches, and amyloid-related imaging abnormalities (ARIAs), an adverse event specific to amyloid-lowering antibodies that can cause temporary brain swelling and small bleeding spots.

ARIAs may not result in symptoms but can sometimes cause headaches, confusion, dizziness, vision changes, and nausea. In rare cases, they can be life-threatening, so Leqembi’s label comes with a warning about their risk.

The boxed warning also says the risk is higher in patients with two copies of a gene variant called APOE4, which is linked to a higher risk for Alzheimer’s, so genetic testing is recommended before treatment.

To inform the Alzheimer’s community on managing and monitoring ARIAs, Eisai has developed a medical educational portal called Understanding ARIA.

“Eisai will diligently work to educate physicians on the safe and appropriate use of Leqembi to maximize its benefit to people living with early [Alzheimer’s disease] and their families,” Naito said.

Requests for Leqembi’s approval are under review in the European Union, the U.K., Canada, Japan, China, and South Korea.