Axovant dumps nelotanserin in retreat from small molecule R&D

Axovant has halted development of nelotanserin after it missed the primary endpoint in a phase 2 trial in patients with Lewy body dementia. The lackluster data persuaded Axovant to drop the drug and complete its pivot from small molecules to gene therapies.

Roivant, the parent company of Axovant, licensed 5HT2A inverse serotonin receptor agonist nelotanserin from Arena Pharmaceuticals for $4 million upfront in 2015 and initiated midphase trials of the drug in patients with dementia with Lewy bodies (DLB) and Parkinson’s disease dementia. One of the trials reported mixed efficacy data in January, but with its lead program intepirdine imploding, Axovant outlined plans to start a confirmatory trial in DLB.

Those plans, and nelotanserin itself, are now on the scrap heap. The decision to dump nelotanserin was triggered by phase 2 data in DLB patients with REM sleep behavior disorder (RBD), but also reflects wider changes at Axovant since the confirmatory trial was discussed earlier this year.

The phase 2 trial enrolled 34 patients with RBD and randomized them to receive nelotanserin or placebo. Axovant had hoped to show that 28 days of once-daily dosing with nelotanserin reduced the frequency of RBD events, as measured by sleep laboratory video assessment. The trial failed to clear that bar, causing it to miss its primary endpoint.

Axovant emerged from the trial with some signs of encouragement that, in another situation, a drug developer may have used to justify further development. Those signs included positive trends seen in prespecified analyses of sleep diaries and sleep parameters. However, Axovant has moved on.

“While secondary measures of efficacy suggest biologic activity for nelotanserin, Axovant has been focused on developing innovative gene therapies and we will not undertake further clinical studies with our legacy small molecule portfolio, including nelotanserin,” Axovant CEO Pavan Cheruvu said in a statement. “The completion of this study closes a chapter in the company’s history.”

The decision means the pipeline Axovant built on its way to a then-record IPO and the delivery of key data on intepirdine has been swept aside, putting the company all in on its new gene therapy assets. Given Axovant licensed its first gene therapy in June, that represents a whiplash change of direction.

AXO-Lenti-PD, the gene therapy Axovant licensed in June, is now the company’s sole clinical-stage asset. Axovant is testing the gene therapy in a phase 2 Parkinson’s disease trial that is due to deliver data in March. Axovant plans to move a second gene therapy—a treatment for oculopharyngeal muscular dystrophy—into human testing in the second half of next year.  

Shares in Axovant fell more than 20% in premarket trading.