An investigational Alzheimer’s drug intended to potentiate acetylcholine release didn’t pass muster in a global phase 3 study, despite a successful phase 2 trial. Intepirdine on a background of stable-dose donepezil failed to confer any cognitive or functional benefit in patients with mild to moderate Alzheimer’s disease.

Intepirdine blocks the 5-hydroxytryptamine receptor 6 and increases the release of acetylcholine. By giving it on a stable background of an acetylcholinesterase inhibitor, researchers hoped to improve cognition by increasing acetylcholine signaling between neurons. In a modestly successful phase 2b study reported out last summer, intepirdine did confer some cognitive and functional benefits.

The study was scheduled to be presented at the Alzheimer’s Association International Conference, but was pulled at the last minute by Axovant, intepirdine’s manufacturer.  The study randomized 269 patients with mild to moderate AD to placebo or intepirdine at 15 mg or 35 mg/day for 24 weeks. By 12 weeks, patients taking the 35-mg dose had declined 1.6 points less than those on placebo on the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog) and 1.94 points on the Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL). Both differences were statistically significant. The drug moved into a phase 3 study, dubbed MINDSET, at 35 mg.

The drug was safe however, with virtually no between-group difference in the occurrence of or the type of serious adverse events (about 6% in each group). Five patents died during the study; none of the deaths were related to the study drug, according to Clinical Neurology News.