Provide a preliminary assessment of the long term benefit of treatment with BHV-4157 among patients with Hereditary Spinocerebellar Ataxias (SCA) .

Hereditary Spinocerebellar Ataxias are potentially fatal, rare neurodegenerative disorders affecting the cerebellum.  Currently, there are no FDA-approved treatments and there is no cure for SCA.  

The study was comprised of two periods: an 8-week randomization phase, followed by a 48-week open-label extension period.  At the end of the open label phase, investigators in the study requested extending the study, as many of their patients complained of worsening of their symptoms after discontinuation of troriluzole. Therefore, an additional 48 week open label phase was initiated. Subjects were male and female outpatients between the ages of 18-75 years, inclusive, with a known or suspected diagnosis of the following hereditary ataxias: SCA1, SCA2, SCA3, SCA6, SCA7, SCA8 and SCA10.  The current analysis focused on the assessment of change from baseline to 96 weeks in the total SARA score.

In the ongoing, expanded extension phase of BHV4157-201, approximately 77% of the patients who completed the 48-week open label phase participated in the expanded extension phase (N=74). At the end of the initial 48-week open label phase, change from randomization baseline in the total score for the SARA (mean change±SE)was -0.417±0.26. Among patients who completed their 96 week visit, change from randomization baseline the the total score for the SARA (mean change±SE)was -0.45±0.52. These changes contrast to an increase in SARA of approximately 1.0 points per year according to both the European and US Natural History studies (Jacobi et al, Ashizawa et al).

The observed changes suggest a lack of disease progression at 2 years in patients treated with troriluzole versus the expected rate of decline in the SARA in untreated patients of approximately 1 point per year, based on cumulative natural history data.