Positive Topline Phase 3 Data for Lecanemab in Early Alzheimer's

Megan Brooks

September 28, 2022

Lecanemab (Eisai/Biogen), an investigational amyloid-clearing monoclonal antibody, reduced cognitive decline by 27% compared to placebo and decreased amyloid levels in the brain of adults enrolled in a phase 3 trial.

The Clarity AD trial included 1795 adults with early AD and confirmed amyloid pathology in the brain. Treatment consisted of lecanemab 10 mg/kg biweekly or matching placebo.

Treatment with lecanemab met the primary endpoint, reducing clinical decline on the global cognitive and functional scale, the Clinical Dementia Rating–Sum of Boxes (CDR-SB), at 18 months by 27% compared with placebo, with a treatment difference in the score change of -0.45 (P = .00005), the companies report.

Starting as early as 6 months, across all time points, treatment with lecanemab yielded highly statistically significant changes in CDR-SB from baseline compared to placebo (all P < .01).

The study also met all key secondary endpoints with highly statistically significant results compared with placebo (P < .01).

Key secondary endpoints, in comparison with placebo, were change from baseline at 18 months in amyloid levels in the brain measured by amyloid positron-emission tomography, the AD Assessment Scale–cognitive subscale14 (ADAS-cog14), the AD Composite Score (ADCOMS), and the AD Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL).

Imaging Abnormalities Within Expectations

Overall, rates of amyloid-related imaging abnormalities (ARIA) related to lecanemab were "within expectations," the companies said.

The incidence of ARIA related to edema (ARIA-E) was 12.5% in the lecanemab group and 1.7% in the placebo group.

The incidence of symptomatic ARIA-E was 2.8% and 0.0%, respectively, and the rate of cerebral hemorrhage (ARIA-H) was 17.0% and 8.7%. The total incidence of ARIA (ARIA-E and/or ARIA-H) was 21.3% in the lecanemab group and 9.3% in the placebo group.

Full results of the Clarity AD trial will be presented in November at the Clinical Trials on Alzheimer's Congress.

Incremental Benefit

Responding to the findings, the Alzheimer's Association said in a statement that it "enthusiastically welcomes" the positive findings. It noted that these are "the most encouraging results in clinical trials treating the underlying causes of Alzheimer's to date.

"For people in the earliest stages of Alzheimer's, this treatment has the potential to change the course of the disease in a clinically meaningful way. These results indicate lecanemab may give people more time at or near their full abilities to participate in daily life, remain independent and make future health care decisions," the Association added.

Also weighing in, Howard Fillit, MD, co-founder and chief science officer at the Alzheimer's Drug Discovery Foundation, said in a release that "the combination of the biomarker change ― reduced amyloid ― plus slowing of cognitive decline in this study is encouraging news for the 57 million patients around the world living with Alzheimer's.

"However, amyloid-clearing drugs will provide an incremental benefit at best, and there is still a pressing need for the next generation of drugs focused on other targets based on our knowledge of the biology of aging," Fillit cautioned.

"We are optimistic about the future as many of these drugs are in development, with 75% of drugs in the pipeline now targeting nonamyloid pathways of neurodegeneration," he added.

In July 2022, the US Food and Drug Administration accepted Eisai's biologics license application for lecanemab under the accelerated approval pathway and granted priority review. Lecanemab has a prescription Drugs User Fee Act action date of January 6, 2023.

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