Axovant Sciences, a clinical-stage biopharmaceutical company focused on the treatment of dementia, announced preliminary results from the planned interim analysis of the first 11 patients to complete its Phase 2 study of nelotanserin in Lewy body dementia patients. Based on these interim results, Axovant plans to expand patient recruitment in this study and will begin preparations for a Phase 3 registration program expected to start in the second half of 2017.

Phase 2 Study Design

The ongoing Phase 2 study includes patients with either dementia with Lewy bodies (DLB) or Parkinson’s disease dementia (PDD) who experience frequent visual hallucinations with a score of 18 or higher on Mini Mental State Examination (MMSE). This is a double-blind, randomized, placebo-controlled, cross-over design study involving random assignment of patients to a treatment sequence of either placebo followed by nelotanserin or nelotanserin followed by placebo. Treatment periods are 4 weeks each with a 4-week washout period between treatment periods. During the active treatment period, patients receive 40 mg nelotanserin during the first 2 weeks and 80 mg nelotanserin during the subsequent 2 weeks.

The primary outcome measures of the study were extrapyramidal signs as assessed by Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II + III and safety. UPDRS Parts II + III was measured at baseline and at the end of each 4-week treatment period. Secondary outcome measures included observational changes in the severity and frequency of visual hallucinations, including multiple subscales from the Scale for the Assessment of Positive Symptoms (SAPS). SAPS subscales were measured at baseline, at week 2, and at week 4 of each treatment period.

Interim Results

Pre-specified primary endpoints:

The mean change from baseline in the UPDRS Parts II + III exhibited statistically significant improvements (p-value < 0.05) for nelotanserin relative to placebo. This result is consistent across least squares and observed mean changes.

Safety analysis included measurement of the incidence of adverse events. There were no reported drug-related serious adverse events, and there were no adverse events that led to discontinuation of the study medication.

Secondary endpoints:

Secondary endpoints evaluated efficacy on multiple subscales from the SAPS including SAPS-PD, SAPS-PD-H, and SAPS-H. Axovant evaluated an internally developed, proprietary secondary endpoint to measure episodes of hallucinations using a patient diary. In this interim analysis, these secondary endpoints did not demonstrate statistically significant differences for nelotanserin relative to placebo.

Nelotanserin Clinical Development Plan in 2017

Based on these preliminary results, Axovant plans to expand patient recruitment to confirm the treatment benefits observed in the interim results from this ongoing study. Axovant expects the full study to complete in mid-2017 and plans to present detailed results at a scientific meeting in 2017.

In addition, Axovant is exploring nelotanserin as a potential treatment for REM Sleep Behavior Disorder (RBD) in patients with dementia with Lewy bodies. The company expects results from the RBD study in the second half of 2017.

Based on the results of these two studies Axovant plans to commence a Phase 3 registration program in the second half of 2017. As part of its preparations, the company expects to evaluate UPDRS Parts II + III as a potential endpoint for Lewy body dementia patients in Phase 3.

“I am intrigued by the benefits observed on the UPDRS in this study,” says James Leverenz, MD, chair, Scientific Advisory Council of the Lewy Body Dementia Association and director of the Cleveland Lou Ruvo Center for Brain Health at the Cleveland Clinic, in a release. “If a single drug could simultaneously address the motor and neuropsychiatric symptoms of Lewy body dementia, which the published literature suggests may be the case for 5HT2A antagonists, it would represent a unique and important advance for the treatment of this condition. I look forward to reviewing the full dataset later this year.”

“We are pleased with the preliminary results of this small pilot study which supports our belief that nelotanserin could be a promising investigational drug candidate for patients suffering from Lewy body dementia,” says Lawrence Friedhoff, MD, PhD, chief development officer of Axovant Sciences. “We plan to discuss with FDA and other regulators the parameters of a potential Phase 3 registration program while we await results from the full cohort of patients in this study. We will carefully examine whether the UPDRS treatment benefit observed in this interim analysis will be maintained in the final analysis when the remaining patients complete this study.”

Nelotanserin is an investigational drug candidate that has the potential to be a once-daily, orally-administered, potent, and highly selective inverse agonist of the 5HT2A receptor. The 5HT2A receptor biology is associated with motor symptoms and neuropsychiatric disturbances including visual hallucinations—a common occurrence in patients with Lewy body dementia. Axovant is developing nelotanserin to address multiple aspects of Lewy body dementia.