Nelotanserin, the therapy candidate for Parkinson’s disease dementia (PDD) associated with hallucinations and for Dementia with Lewy Bodies (DLB), appeared safe as well as displaying signs of effectiveness, according to a Phase 2 trial (NCT02871427).
Meanwhile, intepirdine, a therapy candidate for Alzheimer’s and DLB, failed to meet its objectives in the Phase 2b HEADWAY trial (NCT02669433) and a pilot Phase 2 study (NCT02910102) that focused on walking and balance.
In the HEADWAY trial, 24-week administration of 35 mg or 70 mg of intepirdine in DLB patients did not produce statistically significant improvements in their movement, cognitive, and global functions, in comparison with placebo-treated patients.
Intepirdine has been well tolerated in all of its studies. But the poor effectiveness results did not come as a surprise. That’s because Axovant announced last year that the Phase 3 MINDSET study (NCT02585934) showed that intepirdine failed to help mild-to-moderate Alzheimer’s patients who were receiving background donepezil therapy.
Concerning the impact of intepirdine in dementia patients with gait and balance problems, 35 mg of intepirdine failed to improve gait speed.
“Based on the totality of intepirdine data to date, there is no evidence to support its further development,” David Hung, chief executive officer of Axovant, said in a news release.
In the case of nelotanserin, researchers looked at the safety of the drug in DLB and PDD patients experiencing visual hallucinations in a pilot Phase 2 study.
Preliminary results revealed nelotanserin seemed to decrease dementia progression in Parkinson’s patients.
Now, when researchers looked at 19 of the DLB patients in the Phase 2 hallucination trial, they reported that nelotanserin improved their movement scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) by 4 points.
After seeing the data, the team analyzed a subset of patients who scored 8 or more, an indication of more severe psychotic symptoms, in the Scale for the Assessment of Positive Symptoms — Parkinson’s Disease (SAPS-PD).
They found that 40 mg of nelotanserin for two weeks, followed by 80 mg for two weeks, resulted in a 1.21-point improvement in SAPS-PD.
After these positive results, “we intend to discuss a larger confirmatory nelotanserin study with the FDA that is focused on DLB patients with motor deficits and more severe baseline psychotic symptoms,” Hung said. “Separately, we will be working with Roivant to build our pipeline to develop other new therapies for patients with neurological conditions who so desperately need them.”
In future trials, Axovant said it may also analyze nelotanserin’s effect on DLB and PDD psychotic symptoms.