Positive Phase III trial for Zydis orally dissolving tablet to treat acute migraine.- Biohaven,

Biohaven Pharmaceutical Holding Company Ltd.announced positive topline results from a randomized, controlled Phase III clinical trial (BHV 3000-303 or Study 303) evaluating the efficacy and safety of its Zydis orally dissolving tablet (ODT) formulation of rimegepant, an oral calcitonin gene-related peptide (CGRP) receptor antagonist, for the acute treatment of migraine.

In Study 303, rimegepant Zydis ODT statistically differentiated from placebo on the two co-primary endpoints as well as the first 21 consecutive primary and secondary outcome measures that were prespecified in hierarchical testing. Consistent with the two previous Phase III clinical trials, Study 303 met its co-primary registrational endpoints of pain freedom and freedom from most bothersome symptom (MBS) at 2 hours using a single dose. Importantly, patients treated with the rimegepant Zydis ODT formulation began to numerically separate from placebo on pain relief as early as 15 minutes, and this difference was statistically significant at 60 minutes (p < 0.0001). Additionally, a significantly greater percentage of patients treated with rimegepant Zydis ODT returned to normal functioning by 60 minutes as compared to placebo (p = 0.0025). Lasting clinical benefit was observed through 48 hours after a single dose of rimegepant on freedom from pain (p < 0.0001), pain relief (p < 0.0001), freedom from the most bothersome symptom (p = 0.0018), and freedom from functional disability (p < 0.0001). Superiority over placebo was also demonstrated in multiple other secondary endpoints. The vast majority of patients treated with rimegepant Zydis ODT (85%) did not use any rescue medications.

The safety and tolerability observations of rimegepant in Study 303 were consistent with the profile previously observed in Studies 301 and 302. In study 303, no single adverse event (AE) occurred in the rimegepant group with an incidence higher than 1.6% and overall rates of AEs were similar to placebo. With regard to liver function tests, one patient treated with placebo and one patient treated with rimegepant showed LFTs greater than 3x ULN in Study 303. Pooled liver function test results across the three pivotal trials (n=3,556) performed to date showed that rimegepant was similar to placebo with regard to aminotransferase (ALT or AST) levels above the upper limit of normal (ULN) and no patients experienced elevations in bilirubin > 2x UL.

The double-blind, randomized, multicenter, Phase III outpatient trial treated 1,375 patients across sites in the United States. Patients were required to have at least a one-year history of migraine (with or without aura), consistent with a diagnosis according to the International Classification of Headache Disorders. The trial was designed to evaluate the efficacy and safety of rimegepant Zydis ODT formulation compared with placebo in the acute treatment of migraine. Patients were given a single 75 mg dose of rimegepant Zydis ODT or a matching placebo. They were instructed to take their study medication when they had a migraine which reached moderate or severe pain intensity.