Biohaven Pharmaceutical has dosed the first amyotrophic lateral sclerosis (ALS) patient with its sublingual formulation of riluzole, BHV-0223, in a pivotal Phase 2/3 trial. The trial aims to demonstrate that BHV-0223’s effects are at least equivalent to Rilutek, an approved tablet formulation of riluzole.
The trial initiation was supported by the U.S. Food and Drug Administration‘s approval of the investigational new drug (IND) application for BHV-0223, granted earlier this month.
“We are excited to advance the unique BHV-0223 Zydis orally dissolving tablet (ODT) formulation into the clinic,” Vlad Coric, MD, CEO of Biohaven, said in a press release. “If positive, the current study will establish the bioequivalence of sublingually administered BHV-0223 and thereby offer patients an optimized formulation with enhanced pharmaceutic properties.”
BHV-0223 is a sublingual ODT formulation of riluzole, designed to reduce the limitations of Sanofi-Aventis’ Rilutek, an FDA-approved formulation of riluzole.
In addition to having somewhat marginal effects of survival, Rilutek must be swallowed and taken at least one hour before, or two hours after a meal, due to potential loss of stability. The difficulties in swallowing experienced by ALS patients and the limitations in administration time make Rilutek far from ideal for these patients.
The new formulation is expected to overcome these limitations, while retaining its therapeutic potential. The new tablets use Catalent’s Zydis disintegrating technology, which allows the rapid disintegration and absorption of the drug through the small vessels below the tongue. This not only allows patients with swallowing difficulties the ability to take the drug, it also prevents adverse interactions with food.
Results of a Phase 1 trial showed that BHV-0223 was safe overall, and a 35 mg dose was associated with less variability in the drug’s blood levels than 50 mg of Rilutek.
The newly initiated Phase 2/3 study will now assess if BHV-0223 behaves in the body in a similar manner as Rilutek, and induces at least equivalent effectiveness and safety results.
In December 2016, the FDA granted the company orphan drug designation for BHV-0223 for the treatment of ALS. Biohaven also has received regulatory feedback from the FDA stating that after this study, no additional efficacy or toxicology studies are needed for BHV-0223’s approval.