Aelis Farma’s hopes of securing a quick, positive decision on a $100 million option payment have gone up in smoke. The French biotech reported the failure of its phase 2b cannabis use disorder (CUD) study Wednesday, prompting its partner Indivior to say it doesn’t currently expect to exercise its option.
Indivior paid $30 million for an option to license the candidate in 2021. The British drugmaker planned to make a decision on AEF0117, a signaling-specific inhibitor of cannabinoid receptor 1 (CB1), after seeing the phase 2b data and hearing what the FDA has to say on clinical endpoints for future studies. However, the failure of the study prompted Indivior to signal its intentions without waiting for the FDA’s feedback.
The prompt dampening of expectations about the likelihood of a deal followed an analysis of clinical data that paints a bleak picture of the prospects of AEF0117. Aelis randomized 333 treatment-seeking people with moderate to severe CUD to receive one of three doses of AEF0117 or placebo for 12 weeks.
Participants used cannabis at least five days a week at baseline. AEF0117 was no better than placebo at reducing use to one day a week, causing the study to miss its primary endpoint. The study also missed secondary endpoints that looked at the proportion of patients who completely abstained or cut their use to two days a week.
Aelis is yet to share the numbers behind the failures but did note “a very low placebo effect for these endpoints.” With AEF0117 failing to beat placebo, the comment suggests there was little improvement on the endpoints in the treatment arms. The data are a blow to the hypothesis that selectively blocking CB1 can decrease cannabis use by inhibiting signaling pathways that drive its intoxicating effects.
The only positives disclosed by Aelis related to safety and tolerability, which was similar in the treatment and placebo groups, and the effect of the highest dose on some secondary endpoints. Aelis reported “consistent positive trends” on quantitative endpoints measuring the total amount of cannabis used and “a nearly statistically significant effect” on measures of anxiety, depression and sleep quality.
Some of the decreases in quantitative measures of cannabis use were statistically significant in people with moderate CUD. The moderate CUD subgroup was small, though, with 82% of participants having the severe form of the disorder.
Aelis is still reviewing the results and is yet to decide on the next steps. Indivior doesn’t intend to take up its option, although it is yet to conclusively abandon the deal, and favorable clinical data could shift its thinking.