Abstract Details

Title Matching-adjusted Indirect Comparison of Troriluzole Versus Untreated Natural History Cohort in Spinocerebellar Ataxia

Topic Movement Disorders

Presentation(s) S35 - Movement Disorders: Hyperkinetic Movement Disorders (5:06 PM-5:18 PM)

Poster/Presentation
Number 009

Background SCAs are rare inherited neurodegenerative disorders characterized by progressive ataxia affecting limb coordination, balance, and speech. BHV4157-206 (NCT03701399) was a pivotal efficacy trial examining troriluzole vs placebo, consisting of a 48-week double blinded period followed by a 3-year open-label extension.

Objective To understand the treatment effect of troriluzole over 3 years in patients with spinocerebellar ataxia (SCA) by conducting a matching-adjusted indirect comparison (MAIC) of troriluzole-treated subjects vs subjects in a pooled natural history cohort.

Design/Methods A MAIC was conducted for all SCA genotypes and SCA3 genotype only, to compare ataxia symptoms over 3 years between troriluzole-treated subjects and an untreated natural history cohort. Patient-level natural history data were weighted to match the overall baseline characteristics of troriluzole-treated subjects (modified-functional Scale for the Assessment and Rating of Ataxia [f-SARA], genotype, sex, age, and age of symptom onset). The between-group least squares (LS) mean change from baseline differences on f-SARA were derived, for years 1, 2, and 3.

Results

A total of 96 troriluzole-treated subjects and 611 untreated natural history subjects informed the all SCA genotype analysis. LS mean change differences in f-SARA for all SCA genotypes were -0.64, -1.16, and -1.34 at years 1, 2, and 3, favoring troriluzole (p=0.0008, <0.0001, and <0.0001 respectively). Thirty-eight troriluzole-treated SCA3 subjects were compared to 205 untreated. LS mean change differences for the SCA3 genotype were -0.75, -1.11, and -1.92, favoring troriluzole (p=0.0181, 0.0009, and <0.0001 respectively). These results indicate greater ataxia-related impairment and clinical decline amongst the natural history cohort compared to troriluzole-treated subjects.

Conclusions Compelling and sustained treatment effects were observed out to 3 years when troriluzole-treated subjects were compared to a matched untreated natural history cohort. These results demonstrate that long-term daily dosing of troriluzole attenuates the progression of disease among subjects with SCA3 over 3-years and, to a lesser extent, for all SCA genotypes.

Authors/Disclosures
Melissa Beiner PRESENTER	Melissa Beiner has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Melissa Beiner has stock in Biohaven Pharmaceuticals.
Lauren Powell (Broadstreet HEOR)	No disclosure on file
Basia Rogula	No disclosure on file
Michele Potashman, PhD (Biohaven)	Dr. Potashman has received personal compensation for serving as an employee of Biohaven Pharmaceuticals.
Victoria Wirtz	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.
Susan L. Perlman, MD (UCLA)	Dr. Perlman has nothing to disclose.
Vladimir Coric	Vladimir Coric has received personal compensation for serving as an employee of Biohaven. Vladimir Coric has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Bioahven. Vladimir Coric has stock in Biohaven. Vladimir Coric has received intellectual property interests from a discovery or technology relating to health care.
Gilbert J. L'Italien	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.