Abstract Details

Title Comparative Effectiveness of Troriluzole Versus Untreated Natural History Cohorts in Spinocerebellar Ataxia Leveraging Propensity Score Matching Methods

Topic Movement Disorders

Presentation(s) P6 - Poster Session 6 (11:45 AM-12:45 PM)

Poster/Presentation
Number 5-012

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.

Authors/Disclosures
Gilbert J. L'Italien PRESENTER	Gilbert J. L'Italien has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Gilbert J. L'Italien has stock in biohaven pharmaceuticals.
Michele Potashman, PhD (Biohaven)	Dr. Potashman has received personal compensation for serving as an employee of Biohaven Pharmaceuticals.
Melissa Beiner	Melissa Beiner has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Melissa Beiner has stock in Biohaven Pharmaceuticals.
Basia Rogula	Basia Rogula has received personal compensation for serving as an employee of Broadstreet HEOR.
Lauren Powell (Broadstreet HEOR)	Lauren Powell has nothing to disclose.
Victoria Wirtz	Victoria Wirtz has received personal compensation for serving as an employee of Biohaven Pharmaceuticals, Inc. Victoria Wirtz has stock in Biohaven.
David Stock	David Stock has nothing to disclose.
Irfan Qureshi, MD (Biohaven Pharmaceuticals)	Dr. Qureshi has received personal compensation for serving as an employee of Biohaven. Dr. Qureshi has stock in Biohaven Pharmaceuticals.
Sheng-Han Kuo, MD, FAAN (Columbia University)	Dr. Kuo has nothing to disclose.
Liana Rosenthal, MD (Johns Hopkins School of Medicine)	Dr. Rosenthal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven Pharmaceuticals. Dr. Rosenthal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Reata Pharmaceuticals. Dr. Rosenthal has received research support from NIH. Dr. Rosenthal has received research support from Gordon and Marilyn Macklin Foundation. Dr. Rosenthal has received research support from The Daniel B. and Florence E. Green Foundation. Dr. Rosenthal has received research support from National Ataxia Foundation. Dr. Rosenthal has received research support from Michael J. Fox Foundation. Dr. Rosenthal has received research support from Pfizer. Dr. Rosenthal has received research support from Biohaven Pharmaceuticals. Dr. Rosenthal has a non-compensated relationship as a Medical Director, ex-officio Member of the Board with National Ataxia Foundation that is relevant to AAN interests or activities.
Susan L. Perlman, MD (UCLA)	Dr. Perlman has nothing to disclose.
Vlad Coric	No disclosure on file
Jeremy D. Schmahmann, MD, FAAN (Massachusettes General Hospital)	Dr. Schmahmann has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. The institution of Dr. Schmahmann has received research support from National Ataxia Foundation. The institution of Dr. Schmahmann has received research support from Biohaven. Dr. Schmahmann has received intellectual property interests from a discovery or technology relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care.

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