Biohaven Pharmaceutical announced positive results from its bioequivalence study with BHV-0223, a sublingual formulation of riluzole. The study was designed to demonstrate pharmacokinetic equivalence of sublingual BHV-0223 compared to the reference listed drug Rilutek (riluzole), which is currently the standard of care treatment for patients with Amyotrophic Lateral Sclerosis (ALS). Topline results confirmed that sublingual BHV-0223 (40 mg) achieves bioequivalent exposures relative to Rilutek (50 mg). In the study, 138 healthy volunteers were administered BHV-0223 and Rilutek under fasted conditions. In the pre-specified primary analysis, BHV-0223 achieved area-under-the-curve and peak exposures of approximately 90% and 113%, respectively, compared to those generated by generic riluzole. The 90% confidence intervals were within the 80% to 125% range that is used to define bioequivalence.
Biohaven is developing BHV-0223 as a potential treatment for patients with ALS. Biohaven previously received regulatory feedback from the FDA that the Section 505(b)(2) pathway is acceptable for BHV-0223 in ALS, and that no additional efficacy or toxicology studies are necessary for submission of a new drug application (NDA) for this indication. With these positive results, Biohaven will advance towards completing an NDA with the goal of submitting in the first half of 2018.
BHV-0223 is designed to meet the needs of patients with ALS. BHV-0223 is a sublingually administered orally dissolving tablet (ODT) that makes use of the unique Zydis ODT fast-dissolve technology. It is being developed under an exclusive, worldwide agreement with Catalent. While riluzole is FDA-approved for ALS, conventional tablets may be difficult to administer to ALS patients, who often have dysphagia or trouble swallowing. By contrast, when BHV-0223 is placed under the tongue, it dissolves in seconds and does not require swallowing. In addition, riluzole is associated with dose-dependent effects on liver tests (transaminases). BHV-0223 offers bioequivalent exposures compared to Rilutek with a 20% lower dose. That is, sublingual administration of 40 mg BHV-0223 results in bioequivalent blood exposures to orally ingested 50 mg tablets of Rilutek. Based on this observation and reduced drug exposure to the liver, BHV-0223 may have a lessened risk for causing liver test elevations.
"We are very excited about favorable results from the current study establishing the bioequivalence of our innovative sublingually administered BHV-0223. Sublingual BHV-0223 is unique in that it is a Zydis orally dissolving tablet (ODT) formulation, that is optimized to allow administration to patients with dysphagia and to provide therapeutic blood levels with a lower milligram dose for all patients suffering from ALS," Vlad Coric, M.D., Chief Executive Officer of Biohaven, said.