Eisai and Biogen said Friday that they will end Phase III studies of the experimental oral BACE inhibitor elenbecestat in patients with early Alzheimer's disease. The companies noted that the decision follows a safety review conducted by a Data Safety Monitoring Board, which recommended that the trials be discontinued due to an unfavourable risk-benefit ratio.
The late-stage programme for elenbecestat consisted of two studies with identical protocols, called MISSION AD1 and MISSION AD2, which enrolled a total of about 2100 patients with mild cognitive impairment or mild Alzheimer's disease with confirmed amyloid pathology in the brain. Patients were randomised to receive either elenbecestat or placebo daily during the 24-month treatment period, with the trials' primary endpoint being the Clinical Dementia Rating Sum of Boxes (CDR-SB).
Lynn Kramer, chief clinical officer of Eisai's neurology business, remarked "we are very disappointed with the news, and intend to learn from these data." The companies indicated that detailed results from the studies will be presented at future medical meetings.
In a similar move earlier this year, Biogen and Eisai halted Phase III studies of the experimental anti-amyloid beta antibody aducanumab, which was being tested in mild cognitive impairment due to Alzheimer's disease and mild Alzheimer's disease dementia, as they were deemed unlikely to meet their primary endpoints. However, the companies noted that the decision on elenbecestat does not impact development of the anti-amyloid beta protofibril monoclonal antibody BAN2401, including the Phase III Clarity AD trial, which was initiated in March in patients with early Alzheimer's disease.
A number of BACE inhibitors have advanced to late-stage testing, including Novartis and Amgen's umibecestat, although in July, the companies discontinued development after observing worsening in some measures of cognitive function. Prior to that, Eli Lilly and AstraZeneca ended Phase III studies of the BACE inhibitor lanabecestat in Alzheimer's disease after an independent Data Monitoring Committee said the trial would probably miss its main goal, with other failures in the drug class including Johnson & Johnson's atabecestat and Merck & Co.'s verubecestat.
For related analysis, see ViewPoints: Maybe this time they'll be lucky- Biogen braces after latest BACE assault.
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