Comparative Effectiveness of Troriluzole Versus Untreated Natural History Cohorts in Spinocerebellar Ataxia Leveraging Propensity Score Matching Methods
Gilbert L'Italien1, Michele Potashman1, Melissa Beiner1, Basia Rogula2, Lauren Powell2, Victoria Wirtz1, David Stock1, Irfan Qureshi1, Sheng-Han Kuo3, Liana Rosenthal4, Susan Perlman5, Vlad Coric1, Jeremy Schmahmann6
1Biohaven Pharmaceuticals, 2Broadstreet HEOR, 3Department of Neurology, Columbia University, 4Department of Neurology, Johns Hopkins School of Medicine, 5Department of Neurology, UCLA School of Medicine, 6Department of Neurology, Massachusettes General Hospital
Objective:
Examine the treatment benefits of troriluzole over 3 years in patients with Spinocerebellar Ataxia (SCA) by conducting a matched comparison of troriluzole-treated subjects vs untreated external controls.
Background:
The SCAs are rare autosomal-dominant neurodegenerative diseases characterized by atrophy of the cerebellum and associated with severe disability and premature death. Study BHV4157-206-RWE (NCT06529146) examines troriluzole effectiveness slowing or delaying progression compared with untreated natural history subjects.
Design/Methods:
Data on troriluzole treatment was obtained from BHV4157-206 (NCT03701399), a 48-week double blinded study with 3-year open-label extension. Three natural history cohorts were leveraged as comparators: CRC-SCA, EUROSCA, and a combined cohort selected from CRC-SCA/EUROSCA. Propensity score matching (PSM) between patient-level natural history data with troriluzole-treated subjects created equipoise, matching on baseline characteristics of: modified-functional Scale for the Assessment and Rating of Ataxia (f-SARA), genotype, CAG length, sex, age, and age of symptom onset. The between-group least squares (LS) mean change from baseline differences on f-SARA were derived at years 1, 2, and 3.
Results:
Comparison of 101 troriluzole-treated subjects and 202 CRC-SCA subjects showed LS mean change differences in f-SARA of -0.45, -0.67, and -0.79 at years 1, 2, and 3, favoring troriluzole (all p<0.005). When compared with subjects from the EUROSCA dataset (N=85 troriluzole vs N=170 EUROSCA; SCA genotypes 1/2/3), LS mean change differences in f-SARA of -0.88, -1.39, and -1.75 were observed at Years 1, 2, and 3, favoring troriluzole (all p<0.0001). Results with the combined cohort were comparable. These results correspond to 50-70% slowing of disease progression (i.e., 1.5 to 2.2 years delay) for troriluzole-treated subjects, compared to the untreated external controls.
Conclusions:
Compelling and sustained treatment effects were observed out to 3 years when troriluzole-treated subjects were compared to 3 different matched untreated natural history cohorts, supporting that long-term daily dosing of troriluzole attenuates the progression of disease among SCA subjects.
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