Axovant Sciences announced Tuesday that a late-stage study of the experimental 5-HT6 receptor antagonist intepirdine in patients with mild-to-moderate Alzheimer's disease who were receiving background donepezil therapy failed to meet its co-primary efficacy endpoints. CEO David Hung said "we are deeply disappointed by these trial results," with the drugmaker's shares plunging up to 75 percent on the news.
The MINDSET trial randomised 1315 patients ages 50 to 85 years with mild-to-moderate Alzheimer's disease on donepezil therapy to receive once-daily oral doses of intepirdine or placebo for 24 weeks. Co-primary efficacy endpoints of the study were change from baseline in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL).
Top-line results showed that after 24 weeks of treatment, change from baseline in cognition was non-significantly improved in the intepirdine group, with 0.36 points on the ADAS-Cog scale, versus placebo. Axovant said there was also "essentially no difference" between the intepirdine and placebo arms in change from baseline in activities of daily living.
The drugmaker noted that among the endpoints examined to date, a significant improvement in favour of intepirdine was only observed for the secondary goal of Clinician Interview-Based Impression of Change plus caregiver interview. The company added that it will continue to work with researchers to conclude the open-label extension portion of the trial.
Axovant's parent company Roivant Neurosciences gained rights to intepirdine, previously known as SB-742457 and as RVT-101, from GlaxoSmithKline in 2014. Some analysts recently estimated that the drug could generate sales of $2 billion or more annually if approved for treating Alzheimer's disease. Meanwhile, Axovant is also developing intepirdine for the treatment of Lewy body dementia, with clinical data from the HEADWAY trial anticipated by the end of the year.
In September 2016, Lundbeck reported that its experimental 5-HT6 receptor antagonist idalopirdine missed the primary and secondary endpoints of the Phase III STARSHINE trial of patients with mild-to-moderate Alzheimer's disease. Prior to that, Axovant shares plunged on news that Pfizer had halted a mid-stage trial of its own investigational 5-HT6 receptor antagonist PF-05212377 after "pre-specified, interim analysis futility criteria were met."
For further analysis, read ViewPoints: Another Alzheimer's setback – Axovant's name added to an unfortunate roll call.
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