Axovant Sciences announced that its investigational drug intepirdine did not meet its primary efficacy endpoints in the Phase 2b HEADWAY and pilot Phase 2 Gait and Balance studies. Separately, the Company’s investigational drug nelotanserin met its prespecified primary endpoint of safety in the pilot Phase 2 Visual Hallucination study. In addition, in this exploratory study, nelotanserin treatment resulted in a positive trend in efficacy in a prespecified intent to treat (ITT) analysis of the motor function scale, the Unified Parkinson's Disease Rating Scale (UPDRS) Part III. Nelotanserin treatment also resulted in an efficacy signal in a post-hoc subset analysis of patients with higher baseline scores on the Scale for the Assessment of Positive Symptoms - Parkinson's Disease (SAPS-PD). In the HEADWAY study of intepirdine in patients with dementia with Lewy bodies (DLB), neither 35 mg nor 70 mg of intepirdine resulted in statistically significant improvements after 24 weeks of treatment compared with placebo-treated patients. In motor function, as measured by the UPDRS Part III, 35 mg of intepirdine caused a 2.01 point worsening versus placebo (p=0.158) and 70 mg of intepirdine caused a 0.74 point improvement versus placebo (p=0.607). In cognition, as measured by the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), 35 mg of intepirdine caused a 0.47 point worsening versus placebo (p=0.653) and 70 mg of intepirdine caused a 0.67 point improvement versus placebo (p=0.527). In global function, as measured by the Clinician Interview-Based Impression of Change plus caregiver interview (CIBIC+), 35 mg of intepirdine caused a 0.15 point improvement versus placebo (p=0.395) and 70 mg of intepirdine caused a 0.07 point improvement versus placebo (p=0.701). Previously defined co-primary endpoints for the HEADWAY study were the CIBIC+ and a computerized cognitive battery (CCB). Intepirdine did not achieve statistical significance on the CCB, with 35 mg of intepirdine resulting in a composite z-score of a 0.38 worsening versus placebo (p=0.452) and 70 mg of intepirdine resulting in a composite z-score of a 0.36 improvement versus placebo (p=0.471). In the study of intepirdine in patients with dementia and gait impairment, 35 mg of intepirdine did not result in any improvement in gait speed (1.90 cm per second worsening versus placebo, p=0.357). Intepirdine was generally well tolerated in these studies. In the pilot study of nelotanserin in patients with DLB and Parkinson’s disease dementia (PDD) who were experiencing visual hallucinations, the primary endpoint was safety, including an assessment of symptoms as measured by the UPDRS. On this primary endpoint, nelotanserin was generally well tolerated. A number of exploratory efficacy assessments were conducted, including the UPDRS Part III; the Scale for the Assessment of Positive Symptoms (SAPS); SAPS-PD; the Patient Global Impression of Change of Visual Hallucinations (PGIC-VH); and an internally developed patient diary. In a prespecified ITT analysis, nelotanserin treatment versus placebo (n=27) resulted in a 3.12 point improvement in the UPDRS Part III with a positive trend (p=0.075, unadjusted). Notably, in a prespecified analysis of the DLB patient subset (n=19), nelotanserin improved the UPDRS Part III by 4.00 points (p=0.041, unadjusted). Although nelotanserin did not significantly improve the SAPS-PD (n=27) in the entire efficacy evaluable population (0.88 point improvement, p=0.519, unadjusted), in a post-hoc subset analysis of patients with a baseline SAPS-PD score greater than 8.0 (n=19), indicating greater severity, 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). Further analyses of these data will be conducted which could yield new insights into the effects of nelotanserin. No other trends of improvement were seen on the full SAPS, PGIC-VH, or in the patient diary. Axovant will work with investigators to appropriately conclude the HEADWAY and MINDSET extension studies.