Evotec was updated by its partner Roche on the initial results of the phase IIb trial with Sembragiline (RG1577, EVT302), a MAO-B inhibitor for the treatment of Alzheimer's disease (AD). In this study, Sembragiline failed to demonstrate benefit on the primary endpoint (Alzheimer's Disease Assessment Scale—Cognitive Behaviour 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. The multicenter, randomized, double-blind, parallel-group, placebo-controlled phase IIb study was undertaken to evaluate the efficacy and safety of Sembragiline in patients with moderate severity Alzheimer's disease added on background of AD standard therapy.
Dr. Werner Lanthaler, CEO of Evotec, said, "Clearly disappointing news that Sembragiline didn't reach its primary endpoint but Alzheimer's is one of the biggest medical challenges of our times, and will remain a priority for Evotec and our partners. Strategically, this program represents one out of more than 70 product opportunities within our portfolio in the fields of CNS and pain, metabolic diseases, oncology and anti-infectives."
The news has no impact on Evotec's financial guidance. In 2015, total group revenues excluding milestones, upfronts and licenses are expected to increase more than 35%. Evotec's Group EBITDA before changes in contingent considerations is expected to be positive. Evotec expects R&D expenses to grow to $16.6 million to $22.1 million. Liquidity is expected to be well in excess of $110.7 million at Dec. 31. 2015.
The compound 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. Roche paid Evotec an upfront fee of $10 million. Roche is responsible for all costs, clinical development, manufacturing and commercialization activities.
Sembragiline (RG1577, EVT 302) is a novel, potent inhibitor 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 AD as demonstrated by the up-regulation of MAO-B expression in the brain of AD patients. For these reasons, the selective MAO-B inhibitor is targeted to treat AD symptoms and potentially slow disease progression.