Cortexyme’s Phase 2/3 GAIN Trial of Atuzaginstat (COR388) in Patients with Alzheimer’s Disease Successfully Advances Past Interim Analysis
Cortexyme, Inc. (Nasdaq: CRTX), a clinical stage biopharmaceutical company pioneering potential therapeutics for Alzheimer’s and other degenerative diseases, today announced that the independent Data Monitoring Committee (DMC) conducted a pre-planned interim analysis and recommended Cortexyme continue the Phase 2/3 GAIN Trial of atuzaginstat (COR388) as planned to the 1-year endpoint.
The interim analysis included approximately 300 patients who have reached 6 months of treatment in the GAIN Trial, a randomized, double-blind, placebo-controlled study of 40 and 80 mg BID of atuzaginstat. As part of the interim analysis, the DMC looked for futility, overwhelming efficacy (p< 0.005 on both co-primary outcomes), a sample size increase if needed to improve powering, as well as safety. Based on the interim analysis, topline data for the fully enrolled population of 643 subjects after the full 1-year treatment period is expected on time in December of 2021. The company remains blinded to all data.
Dr. Marwan Sabbagh, Director of the Cleveland Clinic Lou Ruvo Center for Brain Health and Principal Investigator of the GAIN trial said: “Given the tremendous unmet need in Alzheimer's disease, it is imperative that we rapidly and efficiently study potential new treatments. We look forward to completing the study and sharing the results with the medical community and patients when the full trial results become available.”
“We are pleased with the DMC recommendation, which we believe supports the study design and statistical powering of the GAIN Trial. The totality of evidence around P. gingivalis and gingipain inhibition shows that blocking this upstream target may impact multiple aspects of disease progression and neurodegeneration,” said Michael Detke, M.D., Ph.D., Cortexyme’s Chief Medical Officer. “We are grateful to the DMC, the trial investigators, and the patients and caregivers for their participation in the trial as the study continues to its 1-year endpoint.”
Atuzaginstat targets the toxic proteases, or gingipains, produced by P. gingivalis, which have been discovered in greater than 90% of AD patients and shown to produce Alzheimer’s pathology and neurodegeneration in infected animals. P. gingivalis is best known as a keystone bacterium in the development of periodontal disease.
The GAIN (GingipAIN Inhibitor for Treatment of Alzheimer’s Disease) Trial is a Phase 2/3 trial evaluating the efficacy, safety, and tolerability of atuzaginstat (COR388), Cortexyme’s investigational gingipain inhibitor, in patients with mild to moderate Alzheimer’s disease. The co-primary endpoints for the GAIN trial are mean change in ADAS-Cog 11 and ADCS-ADL from baseline to 48 weeks versus placebo. Secondary and exploratory endpoints include change in CDR-SB, NPI, MMSE, Winterlight Speech Assessment, MRI volumetric measures and biomarkers of infection. The GAIN Trial also includes a sub-study measuring the efficacy of COR388 on symptoms of periodontal disease including gingival pocket depth. For more information on the trial, visit www.gaintrial.com.