BioHaven Pharmaceuticals announced the outcome from a focused analysis of the topline co-primary and key secondary data from its Phase 2/3 clinical trial of troriluzole as a symptomatic treatment in mild-to-moderate Alzheimer’s disease (AD). Additional secondary and exploratory efficacy analyses and biomarker data including neurofilament light chain (NfL), neurogranin, tau and amyloid are still pending and expected in the coming months.
The randomized, double blind, placebo-controlled trial enrolled 350 patients with mild to moderate AD. The patients received titrated doses of BHV-4157 to 280 mg, or placebo, taken orally once daily for 48 weeks. Troriluzole did not statistically differentiate from placebo at 48 weeks on the study’s prespecified co-primary endpoints on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-cog) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) in study participants with mild-to-moderate AD. Troriluzole also did not differentiate from placebo on the key secondary measure of hippocampal volume assessed by magnetic resonance imaging (MRI) in the overall population.
A subgroup analysis consisting only of mild AD patients did reveal that troriluzole exhibited a nonsignificant numerical difference of a potential benefit at week 48 on both the ADAS-cog and hippocampal volumetric MRI. Biohaven is planning to amend the ongoing long-term extension study of troriluzole in AD for mild AD patients to be able to continue treatment in order to gather additional clinical and biomarker data. This data will help to determine whether any further study in early AD is warranted. Full study results, including additional secondary and exploratory outcomes, biomarker, and subgroup analyses, are expected in the coming months and will be presented at an upcoming scientific meeting.
Troriluzole is a third-generation prodrug and new chemical entity that modulates glutamate, the most abundant excitatory neurotransmitter in the human body. The primary mode of action of troriluzole is reducing synaptic levels of glutamate. Troriluzole increases glutamate uptake from the synapse, by augmenting the expression and function of excitatory amino acid transporters (i.e., EAAT2) located on glial cells that play a key role in clearing glutamate from the synapse. Glutamatergic dysfunction is implicated in the pathophysiology of a broad range of disorders including Amyotrophic Lateral Sclerosis (ALS), Spinocerebellar Ataxia (SCA), Alzheimer’s Disease (AD), depression, Obsessive Compulsive Disorder (OCD), chronic pain, and a variety of cancers.