Biohaven Pharmaceutical reported negative topline results from its Phase 3 clinical trial evaluating troriluzole compared to placebo for the treatment of patients with Generalized Anxiety Disorder (GAD). This eight-week trial randomized 402 adult patients equally at more than 45 centers in the United States. In this trial, troriluzole monotherapy at 100mg twice daily did not differentiate from placebo on the primary endpoint of the mean change from baseline on the Hamilton Anxiety Rating Scale (HAM-A) after eight weeks of treatment.
"While these efficacy results were disappointing and do not support continued development of troriliuzole as a monotherapy in GAD, we have multiple ongoing studies evaluating troriluzole in other disease indications and with different dosing paradigms,” Vlad Coric, M.D., Chief Executive Officer of Biohaven, said. “Since it is often difficult to predict clinical outcomes from preclinical and early clinical proof of concept studies, our strategy has been to test troriluzole in four distinct disorders where glutamate has been implicated in the underlying pathophysiology of the illnesses. We eagerly await topline data from our adjunctive therapy trial in OCD, and our symptomatic treatment trials in Alzheimer's disease and Spinocerebellar Ataxia. We thank the patients and clinical investigators who participated in the GAD program and sincerely appreciate all that they have done to see this study through completion."
After eight weeks of treatment, troriluzole treated subjects had a mean improvement change from baseline of -9.28 points [95% CI: -10.23 to -8.32] on the HAM-A total score versus -9.35 points [95% CI: -10.34 to -8.36] on placebo, p-value = 0.917. Troriluzole was well tolerated with a low discontinuation rate due to adverse events (troriluzole 4% versus placebo 4.5%).
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"Although the efficacy results are disappointing, the team conducted a well-designed study that provided us with definitive data. We are grateful to the community of patients and researchers who participated in this trial and allowed us to efficiently enroll the study in under 10 months," Loren Aguiar, M.D., Vice President of Research and Development said.
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 normalizing 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.