Early reports in December showed BAN2401 failed to meet primary endpoint. Despite the miss Eisai/Biogen kept on, playing out the trail to the prespecified 18 month end. Phase 2 trial tested 5 different dose regimens of BAN2401 the anti-amyloid beta protofibril antibody in 856 Alzheimer’s patients; after 18 months only the highest dose at 10 mg/kg biweekly only tested on 161 patients showed significant benefit slowing decline by 30% as measured by ADCOMS and 47% as measured by ADAS-Cog. Lower doses of 2.5 and 5 mg/kg doses faired worse results numerically than placebo.
Second BAN2401 clinical trial demonstrated clearance of amyloid from the brain and cognitive benefits, but the clinical trials were not large enough to demonstrate definitely cognitive efficacy and BAN2401 studies did not meet primary endpoint. That being said this is an indicator that amyloids remain an important therapeutic target to pursue, this study had shown successful statistically significant results further validating amyloid hypothesis.
Based on the amyloid hypothesis BAN2401 asserts buildup of amyloid beta proteins in the brain that triggers processes leading to cognitive decline and destruction of brain cells. Relying on amyloid plaques and tau tangle as targets sadly the field has not had new treatment approved in over 15 years. To date every known amyloid targeting drug has failed to modify disease in late phase trials. Alternative hypotheses are being pursued such as one linking amounts of herpes virus in the brain as presence of Alzheimer’s markers.
Another hopeful to fail include a pair of BACE inhibitors, one from Biogen and Eisai the other from Janssen who dropped its atabacestat after clinical trials showed liver safety issues stating the benefit risk ratio was no longer favorable to continue development. The Eisai/Biogen elenbecestat drug failed to slow decline of clinical symptoms more so than placebo in exploratory endpoints. The search continues to find successful therapy to this devastating disease.
