Abstract Details

Title Troriluzole Exhibits Favorable Hepatic Safety Profile Across a Diverse Range of Disorders

Topic General Neurology

Presentation(s) P4 - Poster Session 4 (11:45 AM-12:45 PM)

Poster/Presentation
Number 4-013

Objective Characterize the hepatic safety profile of troriluzole from an extensive clinical program
across a diverse range of disorders.

Background Troriluzole, a novel, optimized prodrug of the glutamate modulating agent riluzole, was
designed to overcome the liabilities of riluzole (i.e., significant first-pass metabolism, dose-
dependent transaminase elevations, low oral bioavailability, high PK variability and negative
food effect). Approximately 50% of riluzole-treated patients experience increased ALT: 8% >
3xULN and 2% > 5xULN. Elevated ALT leading to discontinuation and fatal hepatic injury have
been reported with riluzole. Troriluzole bypasses first-pass metabolism reducing riluzole burden
on the liver and is expected to have a superior hepatic safety profile.

Design/Methods Hepatic safety data were analyzed from troriluzole treated participants across 6 completed and ongoing phase 2/3 clinical trials in spinocerebellar ataxia (SCA; n=337), obsessive-compulsive disorder (OCD; n=397), generalized anxiety disorder (GAD; n=335) and Alzheimer’s disease (AD; n=276). Doses studied ranged from 140-280 mg QD for SCA/AD/OCD and 100mg BID for GAD.

Results A total of 1,386 participants received troriluzole 140,200 or 280mg QD or 100mg BID and 1,345 had on-treatment liver function test data. Mean (SD) average daily dose across indications was 205 (45) mg, and mean (SD) treatment duration was 323 (343) days. A total of 35 (2.6%) participants had ALT > 3xULN and 8 (0.6%) had ALT > 5xULN. Liver enzyme increases generally occurred within the first 12 weeks of treatment and resolved fully with continued treatment or with discontinuation. No signal of severe drug-induced liver injury was reported.

Conclusions Troriluzole exhibited a favorable hepatic safety profile in a large clinical trial safety database. The cumulative frequencies of ALT > 3xULN (2.6%) and > 5xULN (0.6%) were substantially lower than those reported for riluzole (8% and 2%, respectively), confirming troriluzole’s hepatic safety advantages.

Authors/Disclosures
Irfan Qureshi, MD (Biohaven Pharmaceuticals) PRESENTER	Dr. Qureshi has received personal compensation for serving as an employee of Biohaven. Dr. Qureshi has stock in 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.
Richard Bertz (Biohaven Pharmaceuticals)	Richard Bertz has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Richard Bertz has stock in Biohaven Pharmaceuticals.
Stephen Kaplita (Biohaven Pharmaceuticals)	No disclosure on file
Rong Yang (Biohaven Pharmaceutical)	No disclosure on file
Azim Munivar (Biohaven Pharmaceuticals)	No disclosure on file
David Stock	David Stock 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.
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.

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