The monoamine oxidase B inhibitor sembragiline missed its primary endpoint in a Phase 2b trial of more than 500 patients with moderate Alzheimer’s disease (see company news release). Developed jointly by Evotec AG in Hamburg, Germany and Roche in Basel, Switzerland, sembragiline, also known as RG1577, EVT302, and RO4602522, was tested in two doses against placebo along with standard AD therapy—acetylcholinesterase inhibitors with or without memantine—to test safety and efficacy.

Monoamine oxidase B inactivates dopamine and generates free oxygen radicals in mitochondria. Evotec previously developed sembragiline to help people stop smoking, because MAO-B inhibitors mimic some of the antidepressant effects of nicotine. However, that hypothesis fell through (Weinberger et al., 2010). Scientists at the company wondered if by reducing oxidative stress in the brain and lessening dopamine-related symptoms, sembragiline might delay progression of AD. Other MAO-B inhibitors—rasagiline and selegiline—are approved for Parkinson’s disease.

After a year of treatment, sembragiline had no impact on the Alzheimer’s Disease Assessment Scale-Cognitive Behavior Subscale (ADAS-Cog). The drug appeared to be well-tolerated by patients, reported the company. Roche is now analyzing outcomes on secondary endpoints, which include changes on activities of daily living and behavioral symptoms.—Gwyneth Dickey Zakaib


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Therapeutics Citations

  1. Sembragiline

Paper Citations

  1. . A double-blind, placebo-controlled, randomized clinical trial of oral selegiline hydrochloride for smoking cessation in nicotine-dependent cigarette smokers. Drug Alcohol Depend. 2010 Mar 1;107(2-3):188-95. Epub 2009 Nov 24 PubMed.

External Citations

  1. Phase 2b trial
  2. company news release

Further Reading


  1. . Dual inhibitors of monoamine oxidase and cholinesterase for the treatment of Alzheimer disease. Curr Top Med Chem. 2013;13(14):1692-706. PubMed.
  2. . Chronic monoamine oxidase-B inhibitor treatment blocks monoamine oxidase-A enzyme activity. J Neural Transm. 2014 Apr;121(4):379-83. Epub 2013 Nov 23 PubMed.