Aankondiging • Sep 28
Bioarctic Ab's (Publ) Announces Positive Topline Results for the Large Global Phase 3 Confirmatory Clarity Ad Study in 1,795 Subjects
BioArctic AB's (publ) announced positive topline results for the large global Phase 3 confirmatory Clarity AD study in 1,795 subjects. The study met the primary endpoint (CDR-SB 1: Clinical Dementia Rating-Sum of Boxes) showing a highly statistically significant reduction of clinical decline. All key secondary endpoints were also met demonstrating highly statistically significant results. Clarity AD is a clinical trial of lecanemab (development code: BAN2401), an investigational anti-amyloid beta (A) 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 amyloidpathology in the brain. The relative risk in Clarity AD of the main side effect associated with anti-amyloid therapies, ARIA, was within expectations. 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 authorization applications in Japan and Europe by the end of the first quarter of 2023. Additionally, Eisai will present the Clarity AD study results on November 29, 2022, at the Clinical Trials on Alzheimer's Disease conference (CTAD) and publish the findings in a peer-reviewed medical journal. Lecanemab treatment met the primary endpoint and reduced clinical decline on the global cognitive and functional scale, Clinical Dementia Rating-Sum of Boxes (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 were 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 measured by amyloid positron emission tomography (PET), the AD Assessment Scale-cognitive subscale14 (ADAS-cog 14), AD Composite Score (ADCOMS) and the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS MCI-ADL). 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, andsuperficial 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, the relative risk profile of ARIA for lecanemab was within expectations Clarity AD was a global confirmatory Phase 3 placebo-controlled, double-blind, parallel-group, randomized study in 1,795 people with early AD. The treatment group was administered lecanemab 10 mg/kg bi-weekly, with participants allocated in a 1:1 ratio to receive either placebo or lecanemab. The baseline characteristics of both placebo and lecanemab groups was similar and well balanced. Eligibility criteria allowed patients with a broad range of comorbidities/comedications: hypertension, diabetes, heart disease, obesity, renal disease, anti-coagulants, etc. Eisai's recruitment strategy forthe Clarity AD clinical trial ensured greater inclusion of ethnic and racial populations in the U.S., resulting in approximately 25% of the total U.S. enrollment including Hispanic and African American persons living with early AD. Due to the inclusive eligibility criteria and the successful recruitment of diverse ethnic and racial populations in the U.S., Clarity AD's population is generally comparable to the country's Medicare population. 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 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. In an effort to secure traditional FDA approval for lecanemab as soon as possible, Eisai submitted the BLA through the FDA's Accelerated Approval Pathway so that the agency could complete its review of all lecanemab data with the exception of the data from the confirmatory Clarity AD study. In March 2022, Eisai began submitting application data, with the exception of Clarity AD data, to Japan's Pharmaceuticals and Medical Devices Agency (PMDA) under the prior assessment consultation system with the aim of obtaining early approval for lecanemab so that people living with early AD may have access to the therapy as soon as possible. Eisai aims to file for traditional approval in the U.S., and to submit marketing authorization applications in Japan and Europe by the end of the first quarter 2023.