Phase 3 Clinical Trial Update of Troriluzole for Spinocerebellar Ataxia 

In a phase 3 clinical trial (NCT03701399), participants treated with troriluzole (Biohaven; New Haven, CT) vs placebo for spinocerebellar ataxia (SCA) had no statistically significant difference in disease progression. The modified functional Scale for the Assessment and Rating of Ataxia (f-SARA) was used to measure disease progression. The study population (n=213) had a baseline score of 4.9 on the f-SARA, in those treated with troriluzole or placebo, and at week 48, there was f-SARA scores of 5.1 and 5.2, respectively (P=.76). The study had a population with 41% having SCA type 3.

At week 48, people treated with troriluzole vs placebo had a numerical treatment benefit with a f-SARA score mean change difference of -0.55, nominal P-value=.053, 95% CI: -1.12, .01. In a subgroup who had SCA3 and could walk without assistance at baseline treatment with troriluzole resulted in a least squares (LS) mean change difference -0.71, nominal P-value = .031, 95% CI: -1.36, -0.07 compared with placebo.

Across all types of SCA, among those who could walk at baseline, treatment with troriluzole vs placebo reduced patient-reported falls by 58% (10% vs 23%; nominal P=.043).

Dr. Susan Perlman, director of Ataxia Clinic and Neurogenetics Clinical Trials at the David Geffen School of Medicine at UCLA stated, "The f-SARA scale, with a total of 16 points, was specifically designed to detect significant clinically meaningful change in this patient population. The f-SARA change in the SCA3 troriluzole treated group is compelling. Given the excellent safety profile of troriluzole, and the fact that there are no approved treatment options for patients with this devastating neurodegenerative disorder, I am thrilled for my patients that Biohaven is planning to engage with the FDA to potentially move this program forward."

Vlad Coric, MD, chief executive officer and chairman of Biohaven stated, "The fact that the overall study population did not show significant disease progression on the f-SARA at 1 year, as would have been anticipated, and failed to meet the study's primary outcome measure, highlight some of the challenges of studying rare diseases such as SCA. However, the post hoc analyses by SCA genotype suggest early and sustained improvements in the f-SARA over 48 weeks for SCA3 patients treated with troriluzole compared to placebo. The scale improvements were clinically meaningful, consistent with the role that glutamate excitotoxicity is thought to play in the underlying pathogenesis of this disease and was associated with an important risk reduction in falls in the same SCA3 study population, as well as across all SCA genotypes. Patients with SCA3 have no approved therapies and suffer severe disease-related morbidities, including being at high risk for falling due to incoordination of gait. Given the debilitating nature of this disease, we look forward to sharing the SCA3 genotype data with regulators and working with the FDA to address the high unmet need in this patient population."