In people with mild to moderate Alzheimer's disease, the experimental drug EVP-6124 (EnVivo Pharmaceuticals), a selective, partial, alpha-7 nicotinic agonist, showed statistically significant benefits on several cognitive scales. The six-month, Phase 2b trial results were reported at the Alzheimer's Association International Conference® 2012.

EVP-6124 is a selective, partial, alpha-7 nicotinic agonist that, in previous testing, has demonstrated cognitive benefits in normal volunteers and in preliminary study participants with schizophrenia or Alzheimer's.  This is a symptomatic drug with a different mechanism of action than the current FDA-/EMA-approved Alzheimer's drugs.

Alpha-7 nicotinic agonists amplify the effects of acetylcholine, a brain chemical that is essential for normal brain and memory function. Acetylcholine is greatly reduced in people with Alzheimer's. While other approved drugs also have this effect, alpha-7 nicotinic agonists achieve the result by a different mechanism of action.

Dana Hilt, M.D., Senior Vice President of Clinical Development and Chief Medical Officer of EnVivo and colleagues at the company conducted a 6-month, double blind, placebo-controlled, Phase 2b study of three doses of EVP-6124 in 409 people with mild to moderate Alzheimer's who were either on stable Alzheimer's therapy (donepezil or rivastigmine) or on no therapy. [Placebo (n=104), 0.3 mg/d (n=104), 1 mg/d (n=101), 2 mg/d (n=100).]

Primary efficacy endpoints were two established and accepted scales for measuring memory, language, attention and other cognitive abilities (ADAS-Cog-13 and the CDR-SB). Additional pre-specified endpoints included several measures of cognition, language, mood, and ability to function independently (ADAS-Cog-11, COWAT, CFT, NPI, ADCS-ADL (23)), plus composite measures for cognition, memory, and executive function.

After 23 weeks of treatment, the researchers found that, compared to the placebo group, the 2 mg treatment group had statistically significant benefits on the ADAS-Cog-13 and CDR-SB. They also saw a significant effect on the ADAS-Cog 11, COWAT, cognition composite, memory composite, and executive function composite. They reported that EVP-6124 was safe and well tolerated with some mild to moderate gastrointestinal side effects in a minority of patients in both the 1 and 2 mg dose groups.

"In our study, EVP-6124 provided significant benefits for people with mild to moderate Alzheimer's whether they were on currently-approved therapy or not," Hilt said. "While the currently approved Alzheimer's drugs provide modest improvement in cognition and function, additional symptomatic therapies are desirable. We believe that, with further testing, EVP-6124 potentially could be used as a monotherapy or added on to other approved Alzheimer's drugs. These results support studying the drug in further Phase 3 studies."