Evotec, Roche Report Disappointing Results for Late-Stage Alzheimer’s Drug
Evotec AG, a drug-discovery company reports its partner Roche, reported disappointing results on the initial results of a Phase IIb trial with sembragiline, a MAO-B inhibitor for the treatment of Alzheimer’s disease. Sembragiline was originally licensed from Roche to Evotec in 2006, and initially developed in another indication. In 2011, Evotec and Roche entered into an exclusive worldwide agreement for the development and commercialization in patients with Alzheimer’s disease. Under that agreement, Roche paid Evotec an upfront fee of $ 10 million. Roche is responsible for all costs, clinical development, manufacturing,and commercialization activities.
In the recent Phase II study, sembragiline failed to demonstrate benefit on the primary endpoint (Alzheimer’s Disease Assessment Scale, Cognitive Behavior Subscale, ADAS-cog-11) after 52 weeks of treatment. Preliminary safety analyses showed that sembragiline was well tolerated with no safety signals identified. Roche has initiated a process to evaluate all secondary endpoint read-outs on sembragiline and to consider all further development options.
Sembragiline is an ihibitor of monoamine oxidase type B (MAO-B), an enzyme that breaks down the chemical messenger dopamine in the brain and contributes to the production of free radicals. Free radicals are known to cause oxidative stress which may contribute to pathogenesis of Alzheimer’s disease as demonstrated by the up-regulation of MAO-B expression in the brain of Alzheimer’s patients. For these reasons, the selective MAO-B inhibitor is targeted to treat Alzheimer’s disease symptoms and potentially slow disease progression.