Phase 2/3 Study of Troriluzole Shows No Statistically Significant Effects on Alzheimer Disease

A phase 2/3 clinical trial (NCT03605667) of troriluzole (BHV-4157; Biohaven Pharmaceutical, New Haven, CT) has shown no statistically significant effects for symptomatic treatment of mild-to-moderate Alzheimer disease (AD). For those treated with troriluzole vs placebo, there was no statistically significant difference on the AD Assessment Scale-Cognitive Subscale (ADAS-Cog), the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), nor the measure of hippocampal volume assessed by MRI in the overall population. 

Participants with mild AD (n=48) in a subgroup analysis had a nonsignificant numerical difference suggesting a potential benefit at week 48 on both the ADAS-Cog and hippocampal volumetric MRI. In these individuals, the mean deformation change from baseline hippocampal volume was -1.1% compared with -1.6% for those treated with placebo (n=49) [difference -0.5%, P=0.2] at week 48. More analyses and biomarker data may be informative and help determine whether to further the study. Study results, such as biomarker and subgroup analyses, will be presented at a future scientific meeting.

Vlad Coric, MD, chief executive officer of Biohaven commented "Alzheimer is a devastating disease and we must continue to advance the science to improve treatment outcomes for the many patients who are in need. Our goal was to efficiently assess whether troriluzole could benefit patients relatively late in the disease process with mild-to-moderate AD. This study was well-conducted but unfortunately it is clear from this preliminary analysis that troriluzole is not efficacious as a symptomatic treatment in a mixed population of patients with mild and moderate AD. We are awaiting additional biomarker data and other secondary analyses that will help inform whether troriluzole may provide benefit in early AD as a disease-modifying agent. We would like to thank the AD Cooperative Study (ADCS) at the University of California, San Diego for its leadership in AD research and for their collaboration with the Biohaven R&D team to complete this trial. The ability to efficiently assess drug candidates for AD is essential to advancing the field. Biohaven remains deeply committed to developing novel medicines for people suffering from devastating neurological and neuropsychiatric diseases."

Troriluzole treatment at a dose of 280 mg once daily was relatively well tolerated and demonstrated a safety profile consistent with prior studies. An ongoing long-term extension study of troriluzole is planned for participants to continue treatment in order to gather additional clinical and biomarker data.