Despite Concerns, FDA Grants Lecanemab Accelerated Approval for Early Alzheimer Treatment

The US Food and Drug Administration (FDA) has approved LEQEMBI™ (lecanemab-irmb) via the Accelerated Approval pathway for the treatment of early Alzheimer disease, makers Eisai and Biogen announced Friday.

“Alzheimer 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. “This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer, instead of only treating the symptoms of the disease.”

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Lecanemab, a monoclonal antibody, is indicated for use in patients with mild cognitive impairment or mild dementia state of the disease. The drug works to clear “sticky” amyloid plaques from the brain by binding to amyloid-beta (Aβ), thought to be a key mechanism in the deterioration experienced in Alzheimer disease. 

The drug is recommended to be administered intravenously every 2 weeks in 10 mg/kg doses to eligible patients with confirmed presence of Aβ pathology prior to initiating treatment. Enhanced clinical vigilance for amyloid-related imaging abnormalities (ARIA) is recommended during the first 14 weeks of treatment with LEQEMBI. Prior to treatment with lecanemab, clinicians should obtain a recent baseline brain MRI (within one year) and perform periodic monitoring with MRI prior to the 5th, 7th, and 14th infusions.

Recent results from the 18-month multicenter, double-blind, phase 3 trial, CLARITY AD study published in The New England Journal of Medicine showed that monoclonal antibody lecanemab reduced amyloid markers and slowed the rate of decline in early Alzheimer disease.

>>READ our initial report of the CLARITY AD study

The study, funded by drug manufacturers Eisai and Biogen, enrolled 1795 participants with early Alzheimer disease ranging from 50 to 90 years of age (mean=71). Patients were randomly assigned on a 1:1 ratio to receive lecanemab or placebo. Compared with the placebo group, which had no reduction of amyloid beta plaque from baseline to week 79, the control group showed a statistically significant reduction.

“[The drug] resulted in moderately less decline on measures of cognition and function than placebo at 18 months but was associated with adverse effects,” said Christopher H. van Dyck, MD, professor of psychiatry, neurology, and neuroscience, School of Medicine, Yale University, and co-authors in the study.

The most common side effects of the drug were infusion-related reactions, headaches, and ARIA in the form of brain swelling and bleeding. Symptoms include headache, confusion, dizziness, vision changes, nausea, and seizure.

While according to study authors, “no deaths [during the trial] were considered by the investigators to be related to lecanemab or occurred with ARIA,” 2 deaths that occurred after the conclusion of the 18-month trial raised concerns. Experts questioned how the drug would perform in the general population and whether the FDA would grant accelerated approval.

One participant’s death was summarized in an unpublished case report on Science.org and indicated possible drug interactions between lecanemab and tPA. The second patient, a man in his late 80s taking the prescribed blood thinner apixaban (Eliquis), died of a brain hemorrhage in October. Some experts question whether the episode may be linked to an interaction between apixaban and lecanemab.

“It is Eisai’s assessment that the deaths cannot be attributed to lecanemab,” the company said in a statement about the deaths, citing existing medical conditions and medication use in the 2 individuals.

In addition to the open-label extension study, the AHEAD 3-45 clinical trial is evaluating whether lecanemab is an effective and safe treatment for patients with preclinical Alzheimer disease and patients with early preclinical Alzheimer disease. Results from the placebo-controlled, double-blind, parallel-treatment arm, 216-week study are expected in October 2027.

References

FDA grants accelerated approval for alzheimer’s disease treatment. News Release. US Food & Drug Administration. January 6, 2023.

FDA approves LEQEMBI™ (lecanemab-irmb) under the Accelerated Approval pathway for the treatment of Alzheimer’s disease. News release. Eisai and Biogen. January 6, 2023.

Belluck P. Alzheimer’s drug may benefit some patients, new data shows. The New York Times. Published online November 29, 2022. Accessed December 5, 2022.  

Eisai, Inc. AHEAD 3-45 Study: A study to evaluate efficacy and safety of treatment with lecanemab in participants with preclinical Alzheimer’s disease and elevated amyloid and also in participants with early preclinical Alzheimer’s disease and intermediate amyloid. NCT04468659. July 13, 2020. Accessed December 5, 2022. https://clinicaltrials.gov/ct2/show/NCT04468659.

Eisai presents full results of lecanemab phase 3 confirmatory Clarity AD study for early Alzheimer’s disease at clinical trials on Alzheimer’s disease (Ctad) conference. News release. Biogen. November 29, 2022. Accessed December 5, 2022.

George J. Alzheimer’s drug slows decline, trial data shows. MedPage Today. Published online November 30, 2022. Accessed December 5, 2022.

George J. Second trial participant dies in Alzheimer’s drug study. MedPage Today. Published online November 29, 2022. Accessed December 5, 2022.

Howard J. Experimental drug appears to slow progression of Alzheimer’s disease in clinical trial but raises safety concerns. CNN. Published online November 30, 2022. Accessed December 5, 2022.

Neergaard L. Drug slows Alzheimer’s but can it make a real difference? Associated Press. Published online November 30, 2022. Accessed December 5, 2022.