Assessing Effects of BHV-0223 40 mg Zydis® Sublingual Formulation and Riluzole 50 mg Oral Tablet on Liver Function Test Parameters Utilizing DILIsym®

Authors: Longo DM, Shoda LKM, Howell BA, Coric V, Berman RV, Qureshi IA
Conference: American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM)
Keywords: Amyotrophic lateral sclerosis (ALS), hepatoxicity, liver exposure, liver function, liver toxicity, neurodegenerative disease, riluzole oral tablets
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Background

  • Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of motor neurons that leads to progressive muscle weakness and difficulties in speaking, swallowing, and breathing.
  • Riluzole prolongs survival and time to tracheostomy in patients with ALS via a number of potential mechanisms, including reduction of glutamate excitotoxicity.
  • Riluzole can cause dose-related abnormalities in liver function tests.
  • Approximately 50% of patients receiving riluzole oral tablets experience elevated alanine transaminase (ALT) levels, with 8% above 3 x upper limit of normal (ULN) and 2% above 5 x ULN.
  • BHV-0223 is a novel investigational 40 mg sublingually dissolving Zydis® formulation of riluzole that is bioequivalent to the riluzole 50 mg oral tablet formulation.
  • Because of its sublingual route of administration, BHV-0223 bypasses first-pass metabolism, achieving adequate drug concentrations with diminished drug burden and potentially less risk of liver toxicity.
  • DILIsym® (DILIsym Services, Inc, Research Triangle Park, NC) is a validated multi-scale computational model that supports evaluation of liver toxicity risks

2018 AANEM Annual Meeting | October 10-13 | Washington, DC

By Diane M. Longo, Lisl K. M. Shoda, Brett A. Howell, Vladimir Coric, Robert M. Berman, Irfan A. Qureshi