Biohaven Ltd. has announced positive topline results from its pivotal Study BHV4157-206-RWE, demonstrating the efficacy of troriluzole in slowing the progression of spinocerebellar ataxia (SCA). The study, which compared troriluzole-treated patients to matched, untreated external controls, showed a significant slowing of disease progression over a three-year period. This offers hope for a condition with no currently approved treatments.
The trial data indicated a 50-70% reduction in the rate of decline in SCA patients treated with troriluzole compared to the control group, translating to a 1.5-2.2 year delay in disease progression over the study period. The results were consistent across nine pre-specified primary and secondary endpoints.
Clinical Significance
"SCA is a debilitating, relentlessly progressive disease that destroys quality of life, leaving patients unable to care for themselves, walk, or speak," said Susan Perlman, MD, Director of the Ataxia Clinic and Neurogenetics Clinical Trials at the David Geffen School of Medicine at UCLA. "Troriluzole is the very first treatment to show a delay in disease progression that can give patients additional years of independence."
Study Design and Results
The Study BHV4157-206-RWE was designed in consultation with the FDA to assess the effectiveness of troriluzole in SCA over three years, as measured by the change from baseline in the modified functional Scale for the Assessment and Rating of Ataxia (f-SARA). The study utilized Phase 3 data and an external control of matched, untreated SCA subjects from the US Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA), in accordance with FDA's Guidance on Real-World Evidence (RWE) of effectiveness.
The primary objective was to examine the treatment effects of troriluzole for up to 3 years, by comparing data on the f-SARA from patients treated with troriluzole in Study BHV4157-206 to untreated patients from the natural history study. Troriluzole-treated patients demonstrated statistically significant and sustained benefits at years 1, 2 and 3 on the f-SARA compared to a rigorously matched natural history control.
In a responder sensitivity analysis, disease progression when defined by a 2 point or greater worsening on the f-SARA at 3 years showed an odds ratio (OR) of 4.1 (95% CI: 2.1, 8.1) for the untreated external control arm versus troriluzole treated subjects (p < 0.0001; pooled analysis).
Regulatory Pathway
Based on the topline data from Study BHV4157-206-RWE, Biohaven plans to submit a New Drug Application (NDA) to the FDA in Q4 2024 for troriluzole in the treatment of all SCA genotypes. The application is eligible for priority review given orphan drug and fast-track designations previously granted by FDA.
"Advancing new therapies for patients with rare diseases is often a multiyear process of collaboration across academic, patient advocacy, regulatory and industry partners," said Vlad Coric, M.D., Chief Executive Officer and Chairman of Biohaven. "We look forward to interacting with regulatory agencies to bring troriluzole to patients with SCA."
About Spinocerebellar Ataxia
Spinocerebellar ataxia (SCA) is a group of dominantly inherited neurodegenerative disorders characterized by progressive loss of voluntary motor control and atrophy of the cerebellum, brainstem, and spinal cord. Patients experience significant morbidity, including progression to a wheelchair, impaired gait leading to falls, inability to communicate due to speech impairment, difficulty swallowing, and premature death. Currently, there are no FDA-approved treatments and no cure for SCA. It affects about 15,000 people in the U.S. and 24,000 in Europe and the U.K.
