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 RM, Qureshi IA
Conference: DILI
Keywords: Amyotrophic lateral sclerosis (ALS), BHV-0223, drug induced liver injury (DILI), liver function, oral drug delivery, riluzole oral tablets
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Premise

  • 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.
  • Approximately 50% of patients receiving riluzole oral tablets experience elevated alanine transaminase (ALT) levels, with 8% above 3 upper limit of normal (ULN) and 2% above 5 x ULN.
  • BHV-0223 is a novel 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.
  • This study quantitatively and mechanistically compared the liver toxicity potential of oral riluzole versus BHV-0223, combining clinical and mechanistic data, using DILIsym®.

US FDA & AASLD DILI Conference at the University of Maryland University College May 7-8, 2019

Diane Longo, Lisl Shoda, Brett Howell