The US Food and Drug Administration (FDA) has approved the anti-amyloid beta protofibril antibody lecanemab (Leqembi, Eisai) for the treatment of early Alzheimer’s disease (AD). The agency approved the treatment on the basis of findings from the CLARITY AD trial, which showed modest cognitive benefit for patients with early AD ― but at a cost of increased risk for amyloid-related edema and effusions.

The trial enrolled 1795 adults with mild cognitive impairment or early AD in whom amyloid pathology in the brain had been confirmed. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo. After 18 months of treatment, lecanemab slowed cognitive decline by 27% compared with placebo, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB). This was an absolute difference of 0.45 points (change from baseline, 1.21 for lecanemab vs 1.66 with placebo; P < .001).

While the results are “welcome news,” a 0.45-point difference on the CDR-SB might not be clinically meaningful, authors of a recent editorial in The Lancet cautioned. In addition, as noted, the drug has been associated with adverse events. Amyloid-related imaging abnormalities that manifest as edema or microhemorrhages occurred in 1 in 5 patients taking lecanemab. A newly published case report in The New England Journal of Medicine describes a patient with AD who was taking lecanemab and who died after experiencing numerous intracerebral hemorrhages during treatment with tissue plasminogen activator (tPA) for acute ischemic stroke.

“The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” the authors of that study write.

Like its controversial cousin aducanumab (Aduhelm, Biogen/Eisai), lecanemab was approved under the FDA’s accelerated approval pathway, which can be used to fast-track a drug that provides a meaningful therapeutic advantage over existing treatments for a serious or life-threatening illness. Unlike aducanumab, however, there was no formal FDA advisory committee meeting on lecanemab prior to approval.

“Alzheimer’s disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones,” Billy Dunn, MD, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said 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,” Dunn added.

Eisai has reported that lecanemab will cost $26,500 a year. A “Milestone Achievement” Still, in anticipation of accelerated approval of lecanemab and the anti-amyloid drug donanemab (Eli Lilly), which the FDA has also fast-tracked, the Alzheimer’s Association filed a formal request last month with the Centers for Medicare & Medicaid Services (CMS) asking that it provide full and unrestricted coverage for FDA-approved AD treatments.