FDA Grants Accelerated Approval to Lecanemab for Early Stage Alzheimer Disease

The FDA has granted accelerated approval to lecanemab (Lequembi; Eisai and Biogen) to slow the progression of Alzheimer disease. Today’s FDA action marks the second approval for a new class of medications that target the fundamental pathophysiology of Alzheimer disease. Lecanemab’s indication is only to treat mild cognitive impairment or the mild dementia stage of the disease.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” said Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, in a press release. “This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer’s, instead of only treating the symptoms of the disease.”

In phase 3 clinical trials, the drug showed promise in appearing to inhibit the progression of Alzheimer disease, but there were safety concerns reported for a potential association with certain serious adverse events (AEs), such as brain swelling and bleeding. Lecanemab was evaluated for safety and efficacy in a controlled and randomized phase 3 trial published in The New England Journal of Medicine. The novel treatment was assessed for the ability to reduce the pathological marker, amyloid beta plaque.

The double-blind, placebo-controlled, parallel-group, dose-finding study included 856 participants with Alzheimer disease and accompanying amyloid beta pathology. All the patients exhibited mild cognitive impairment or a mild dementia stage of the disease.

Participants in the intervention arm received a 10 mg/kg dose of lecanemab every 2 weeks, and researchers used positron emission tomography (PET) to quantify the amyloid beta plaque levels present in a composite of brain regions.

In the trial, lecanemab “reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months but was associated with adverse events.” After 79 weeks, the team observed that the lecanemabirmb-arm had a significant decrease in amyloid beta plaque compared to the placebo group, who showed no signs of reduction.

According to the press release, “patients receiving the treatment had significant dose- and time-dependent reduction of amyloid beta plaque.”

In the phase 3 trial, approximately 6.9% of participants administered lecanemab as an intravenous infusion discontinued because of AEs vs 2.9% of patients administered placebo. Serious AEs were reported in 14% of the lecanemab cohort and 11.3% of the placebo cohort.

The most common AEs associated with lecanemab are infusion-related reactions—including flu-like symptoms, nausea, vomiting, changes in blood pressure—headache, and amyloid-related imaging abnormalities (ARIA).

Often not presented with symptoms, ARIA could be serious or life-threatening, according to the FDA, with possible swelling of certain brain areas, small spots of bleeding on the surface of the brain, headache, confusion, dizziness, vision changes, nausea, and seizure.

Alzheimer disease is a progressive brain disorder that decimates thinking and memory skills, irreversibly changing the brain. It has affected more than 6.5 people in the United States, but it’s cause is not fully known. Changes to the brain also include neurofibrillary (tau, tangles) which affects neurons and their ability to make connections.

Advocacy groups applauded the approval but raised concerns regarding access to the drug from the US Centers for Medicare & Medicaid Services and insurance companies.

“What the FDA did today in granting accelerated approval to Leqembi was the right decision. But what CMS is doing by severely restricting coverage for approved treatments is unprecedented and wrong,” said Joanne Pike, DrPH, Alzheimer’s Association president and chief executive officer, in a press release. “The FDA carefully reviewed the evidence for Leqembi before granting approval. CMS, in sharp contrast, denied coverage for Leqembi months ago before it had even reviewed this drug’s evidence. CMS has never done this before for any drug, and it is clearly harmful and unfair to those with Alzheimer’s. Without access to and coverage of this treatment and others in its class, people are losing days, weeks, months—memories, skills and independence. They’re losing time.”

Reference

U.S Food and Drug Administration. FDA Grants Accelerated Approval for Alzheimer’s Disease Treatment. FDA News Release. January 6, 2022. Accessed on January 6, 2022. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-disease-treatment