Axovant’s run of bad news shows no signs of letting up, with negative results in a phase 2b trial in Lewy body dementia (DLB) spelling the end for lead candidate intepirdine.
Prospects for intepirdine were already looking shaky last year when the MINDSET trial showed no benefit for the drug in mild-to-moderate Alzheimer’s disease, and analysts had already relegated the project to speculative status. Now the 5-HT6 inhibitor has suffered terminal setbacks, missing its objectives in the phase 2b HEADWAY trial in DLB, as well as pilot studies looking at gait and balance in dementia patients.
“Based on the totality of intepirdine data to date, there is no evidence to support its further development," said David Hung, M.D., Axovant’s CEO and serial biotech entrepreneur, who added that the company is “incredibly disappointed and saddened for the millions of people living with these difficult conditions.”
Intepirdine—originally licensed from GlaxoSmithKline for the knockdown price of $5 million upfront in 2014—has now gone the way of Lundbeck’s idalopirdine, a 5-HT6 inhibitor that failed in late-stage Alzheimer’s testing in 2016. Both drugs were being developed in Alzheimer’s on the premise that they could boost the effect of older drugs such as cholinesterase inhibitors or NMDA antagonists.
The HEADWAY trial was slightly different, comparing intepirdine as a monotherapy to placebo, including a higher dose than was used in the Alzheimer’s trial.
It’s now turning its attention to ex-Arena drug nelotanserin, and on Monday, Axovant reported a trend toward efficacy and no safety signals in a phase 2 trial in DLB. Nelotanserin—a 5-HT2a receptor inverse agonist—is being tested for its ability to reduce visual hallucinations and sleep disorders in patients with DLB as well as for Parkinson’s disease dementia (PDD).
The drug showed a trend toward improvement on the Unified Parkinson's Disease Rating Scale (UPDRS) part III in PDD patients, suggesting an effect on hallucinations, as well as a benefit in DLB patients that just achieved statistical significance.
The drug wasn’t able to significantly improve the Scale for the Assessment of Positive Symptoms (SAPS-PD) scores in the study, however, although Hung said there was a significant benefit on this measure for patients with more severe disease at enrollment.
But then, a day later, it announced that, actually, it had got the nelotanserin data wrong: "The previously reported data for this population (n=19) that nelotanserin treatment at 40 mg for two weeks followed by 80 mg for two weeks resulted in a 1.21 point improvement (p=0.011, unadjusted) were incorrect," it said in a sheepish admission.
"While nelotanserin treatment at 40 mg for two weeks followed by 80 mg for two weeks did result in a 1.21 point improvement, the p-value was actually 0.531, unadjusted [in the world of stats, a fail]. Based on these updated results, the company will continue to discuss a larger confirmatory nelotanserin study with the U.S. Food and Drug Administration (FDA) that is focused on patients with dementia with Lewy bodies (DLB) with motor function deficits. The Company may further evaluate nelotanserin for psychotic symptoms in DLB and Parkinson’s disease dementia (PDD) patients in future clinical studies."
Shares in Axovant were down nearly 50% in premarket trading Monday morning.