Eisai and Biogen announced positive results from Eisai’s large global Phase 3 confirmatory Clarity AD clinical trial of lecanemab, which met the primary endpoint and reduced clinical decline in early stages of Alzheimer's disease.
Key highlights:
- Lecanemab treatment met the primary endpoint and reduced clinical decline on the global CDR-SB scale by 27% at 18 months, compared to placebo.
- CDR-SB is a numeric scale used to quantify the severity of symptoms of dementia and can evaluate the effectiveness of therapeutic drugs targeting the early stages of AD.
- The clinical study, Clarity AD, was a global confirmatory Phase 3 placebo-controlled, double-blind study in 1,795 people with early AD.
- The study shows that removal of aggregated amyloid beta in the brain is associated with a slowing of disease in patients at the early stages of decline.
Lecanemab (BAN2401) is an investigational anti-amyloid beta (Aβ) protofibril antibody for the treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD (collectively known as early AD) with confirmed presence of amyloid pathology in the brain.
CDR-SB (Clinical Dementia Rating-Sum of Boxes) is a numeric scale used to quantify the various severity of symptoms of dementia in six areas: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The total score is used as an appropriate item for evaluating the effectiveness of therapeutic drugs targeting the early stages of AD.
The results
Lecanemab treatment 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%, which represents a treatment difference in the score change of -0.45 (p=0.00005) in the analysis of Intent-to-treat (ITT) population.
Starting as early as six months, across all time points, the treatment showed highly statistically significant changes in CDR-SB from baseline compared to placebo (all p-values are less than 0.01). All key secondary endpoints were also met with highly statistically significant results compared with placebo (p<0.01).
Key secondary endpoints were the change from baseline at 18 months compared with placebo of treatment in amyloid levels in the brain.
The incidence of amyloid-related imaging abnormalities-edema/effusion (ARIA-E), an adverse event associated with anti-amyloid antibodies, was 12.5% in the lecanemab group and 1.7% in the placebo group. The incidence of symptomatic ARIA-E was 2.8% in the lecanemab group and 0.0% in the placebo group. The ARIA-H (ARIA cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis) rate was 17.0% 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 (i.e. ARIA-H in patients who did not also experience ARIA-E) between lecanemab (8.8%) and placebo (7.6%).
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. Overall, lecanemab’s ARIA incidence profile was within expectations.
The trial
Clarity AD was a global confirmatory Phase 3 placebo-controlled, double-blind, parallel-group, randomised study in 1,795 people with early AD.
The treatment group was administered a dosage of 10 mg/kg bi-weekly of lecanemab, with participants allocated in a 1:1 ratio to receive either placebo or lecanemab.
The wider scope
In July 2022, the U.S. Food and Drug Administration (FDA) accepted Eisai’s Biologics License Application (BLA) for lecanemab under the accelerated approval pathway and granted Priority Review.
“The positive result of the lecanemab, an anti-Aβ protofibril antibody, pivotal study after almost 25 years since Aricept’s launch is an important milestone for Eisai in fulfilling our mission to meet the expectations of the Alzheimer’s disease community.
"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. We believe that helping to alleviate these burdens will positively impact society as a whole,” said Haruo Naito, chief executive officer at Eisai.
“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, chief executive officer at Biogen.
“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."
The road ahead
Eisai will discuss this data with regulatory authorities in the U.S., Japan and Europe with the aim to file for traditional approval in the US and for marketing authorisation applications in Japan and Europe by the end of Eisai’s FY2022, which ends March 31, 2023.
Additionally, Eisai will present the Clarity AD study results on November 29, 2022, at the Clinical Trials on Alzheimer’s Congress (CTAD), and publish the findings in a peer-reviewed medical journal.
The Prescription Drugs User Fee Act action date (PDUFA) is set for January 6, 2023. The FDA has agreed that the results of Clarity AD can serve as the confirmatory study to verify the clinical benefit of lecanemab.
Like this article? Subscribe to the FREE EPM newsletter.