This morning, Axovant announced that Intepirdine failed to meet both primary objectives in the Mindset trial. The press release said,
“After 24 weeks of treatment, change from baseline in cognition was non-significantly improved in the intepirdine arm versus the placebo arm (0.36 ADAS-Cog points; p-value = 0.22). In addition, there was essentially no difference between the intepirdine and placebo arms in change from baseline in activities of daily living (0.09 ADCS-ADL points; p-value = 0.83).”
An improvement of only 0.36 in ADAS-Cog score is substantially lower than the 1.5 improvement that they saw in the Phase II trial (Maher-Edwards G, 2015). What we can assume from this is that the Donepezil control group was substantially more “Donepezil-responsive” than in the Phase II Donepezil group or the combination treatment was just ineffective.
I think the only way this trial could have been a success is if Axovant was more specific in their inclusion criteria. They really needed a group of patients that were losing Donepezil effectiveness (~6 months or more of chronic Donepezil treatment) so that they could maximize the contribution of Intepirdine (if there is efficacy). It still isn’t known whether the combination of 5-HT6 antagonism and acetylcholinesterase inhibition increases human brain acetylcholine more than just acetylcholinesterase inhibition alone. It also isn’t known whether there is a max functional improvement from increased brain acetylcholine, whereby any further increase does not produce functional improvements. These questions are difficult to answer, given the obvious lack of human brain samples for study.
It is disappointing that the trial failed, but I was able to cover my short position this morning and make a 70% return.
AXON’s low of the day was $6.13, so those who sold volatility instead of picking a direction did very well, given the move was less than expected (see my original post). Long-term, the company has other ongoing trials for both Intepirdine and Nelotanserin, which definitely have clinical potential in other diseases. For Alzheimer’s though, it may be wise to look towards other targets. There is still a large unmet need in Alzheimer’s, and the company that takes the risk and succeeds will be rewarded handsomely by the market.