Intepirdine Fails to Meet Topline Goals in Phase 3 Alzheimer's Disease Trial

The phase 3 MINDSET clinical trial of investigational drug intepirdine in patients with mild to moderate Alzheimer’s disease (AD) who were receiving donepezil therapy did not meet its co-primary efficacy endpoints, announced Axovant Sciences.

Patients treated with 35 mg of intepirdine did not experience improvement in cognition or in measures of activities of daily living as measured by the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and by the Alzheimer’s Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL), compared to patients treated with placebo at 24 weeks.

After treatment, change from baseline in cognition was not significantly improved in those receiving intepirdine versus the placebo. Additionally, there was no real difference between both arms from baseline in activities of daily living.

The only endpoint which had any significant improvement was the first key secondary endpoint seen in intepirdine patients, the Clinician Interview-Based Impression of Change plus caregiver interview, or CIBIC+ (.12 CIBIC+ points).

The MINDSET trial evaluated the efficacy, safety and tolerability of intepirdine in patients with mild to moderate AD on donepezil therapy throughout 24 weeks. The trial compared once-daily oral doses of intepirdine 35 mg to placebo in 1,315 patients 50—85 years old. The Mini-Mental State Examination (MMSE) score at baseline ranged from 10–26. Primary efficacy endpoints included ADAS-Cog and the ADCS-ADL.

Axovant is willing to work with investigators to conclude the MINDSET open-label extension study.

Intepirdine, an oral, once-daily drug, is a potent antagonist of the 5-HT6 receptor promoting the release of acetylcholine in the brain, a neurotransmitter critical in alertness, memory, thought and judgement needed for normal cognition.

The company remains committed to advance its phase 2b HEADWAY study of intepirdine, and nelotanserin, a highly selective inverse agonist of the 5-HT2a receptor in phase 2 development, of which are being evaluated in patients with dementia with Lewy bodies. It’s reportedly on track to report topline results end of 2017.

Intepirdine was generally well tolerated in the MINDSET trial and has received Fast Track designation from the US Food and Drug Administration for the treatment of DLB.

A press release was made available.