Lecanemab Shows Highly Statistically Significant Reduction of Clinical Decline in Early Alzheimer Disease
Eisai plans to file for traditional approval in the United States by March 31, 2023.
Results from a confirmatory phase 3 trial of lecanemab for early Alzheimer disease show a highly statistically significant reduction of clinical decline in patients, according to a press release from Biogen.
The study also met all key secondary endpoints, demonstrating highly statistically significant results, and the profile of amyloid-related imagine abnormalities incidence was within expectations. Eisai aims to file for traditional approval in the United States and to submit marketing authorization applications in Japan and Europe by March 31, 2023.
“Today’s announcement gives patients and their families hope that lecanemab, if approved, can potentially slow the progression of Alzheimer’s disease, and provide a clinically meaningful impact on cognition and function,” said Michel Vounatsos, CEO at Biogen, in a press release. “Importantly, the study shows that removal of aggregated amyloid beta in the brain is associated with a slowing of disease in patients at the early stage of the disease.”
Lecanemab is an investigational anti-amyloid beta protofibril antibody for the treatment of mild cognitive impairment due to Alzheimer disease and mild or early Alzheimer disease with confirmatory presence of amyloid pathology in the brain. Clarity AD was a global, confirmatory phase 3 placebo-controlled, double-blind, parallel-group, randomized study with 1795 participants with early Alzheimer disease.
“The lecanemab Clarity [Alzheimer disease] study results prove the amyloid hypothesis, in which the abnormal accumulation of [amyloid beta] in the brain is one of the main causes of Alzheimer’s disease, when targeted with a protofibril-binding therapy,” said Haruo Naito, CEO at Eisai, in a press release. “Eisai believes these findings will create new horizons in the diagnosis and treatment of Alzheimer’s disease as well as further activate innovation for new treatment options.”
The treatment group received lecanemab 10 mg/kg bi-weekly and participants were randomized 1:1 to receive either lecanemab or placebo. The baseline characteristics of both groups were similar and well balanced, including patients with a broad range of comorbidities and comedications.
Lecanemab met the primary endpoint and reduced clinical decline on the global cognitive and functional scale (CDR-SB) compared with placebo at 18 months by 27%, representing a treatment difference in the score change of -0.45 in the intent-to-treat population analysis. Starting as early as 6 months, across all time points, the treatment showed highly statistically significant changes in CDR-SB from baseline compared with placebo.
Key secondary endpoints were the change from baseline at 18 months compared with placebo of treatment in amyloid levels in the brain measured by amyloid positron emission tomography, the Alzheimer disease Assessment Scale-cognitive subscale14, the Alzheimer disease Composite Score, and the Alzheimer disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment.
The incidence of amyloid-related imaging abnormalities-edema/effusion (ARIA-E) was 12.5% in the lecanemab group and 1.7 in the placebo group. This is an adverse event associated with anti-amyloid antibodies.
Similarly, the incidence of symptomatic ARIA-E was 2.8% in the lecanemab group and 0.0% in the placebo group. The rate of ARIA cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis (ARIA-H) rate was 17% in the lecanemab group and 8.7% in the placebo group. The incidence of symptomatic ARIA-H was 0.7% in the lecanemab group and 0.2% in the placebo group.
There was no imbalance in isolated ARIA-H between lecanemab (8.8%) and placebo (7.6%). Finally, the total incidence of ARIA was 21.3% in the lecanemab group and 9.3% in the placebo group. Further, lecanemab’s ARIA incidence profile was within expectations.
“Alzheimer’s disease not only presents a great challenge for patients and their families, but it also negatively impacts society, including decreased productivity, increased social costs, and disease-related anxiety,” Naito said in the press release. “We believe that helping to alleviate these burdens will positively impact society as a whole.”
Lecanemab Confirmatory Phase 3 Clarity AD Study Met Primarily Endpoint, Showing Highly Statistically Significant Reduction of Clinical Decline in Large Global Clinical Study of 1795 Participants with Early Alzheimer’s Disease. News release. Biogen; September 27, 2022. Accessed November 2, 2022. https://investors.biogen.com/news-releases/news-release-details/lecanemab-confirmatory-phase-3-clarity-ad-study-met-primary