Vazegepant Relieves Pain And Most Bothersome Symptoms in Phase 2/3 Trial

In a pivotal phase 2/3 clinical trial (NCT03872453), vazegepant (Biohaven Pharmaceutical, New Haven, CT). Participants in the trial (n=1,673) were randomly assigned to receive 5 mg, 10 mg, or 20 mg of vazegepant or placebo delivered intranasally when they needed acute treatment of migraine. 

Participants treated with vazegepant had rapid onset of pain relief at 15 minutes (10 mg and 20 mg) and return to normal function as early as 30 minutes (20 mg). The 10 mg and 20 mg vazegepant doses showed therapeutic benefits on both pain relief and return to normal function at 2 hours. Intranasal vazegepant was well tolerated in this single-dose trial. Individual adverse events (AEs) greater than 5% were: dysgeusia (13.5 to 16.1% in the vazegepant arms, and 3.5% in the placebo arm) and nasal discomfort (1.3 to 5.2% in the vazegepant arms, and 0.2% in the placebo arm). The majority (> 80%) of AEs were mild in intensity. No participants had AST or ALT > 3x ULN, or total bilirubin > 2x ULN, in any treatment arm.

Vazegepant 10 mg and 20 mg was statistically superior to placebo on the coprimary endpoints of pain freedom (22.5% and 23.1% vs 15.5%; P=.01 and P=.005, respectively). Freedom from most bothersome symptom (MBS) of photophobia, phonophobia, or nausea also occurred in a higher proportion of people treated with vazegepant 2 hours after vausing a single dose. The benefits of vazegepant were durable and sustained without rescue medication through 48 hours (nominal P < .05), including: sustained pain freedom 2 to 24 hours (5 mg, 10 mg, and 20 mg); sustained pain freedom 2 to 48 hours (5 mg, 10 mg, and 20 mg); sustained pain relief 2 to 24 hours (5 mg, 10 mg, and 20 mg); and sustained pain relief 2 to 48 hours (5 mg and 10 mg). 

Richard B. Lipton, MD, professor and vice chair of Neurology, and director of the Montefiore Headache Center, at the Albert Einstein College of Medicine commented, "A large number of patients need a nonoral, acute migraine treatment option, particularly those with prominent nausea, vomiting or gastroparesis. Most of my patients don't like needles. Vazegepant is the 1st CGRP receptor antagonist delivered in an intranasal formulation, a benefit for patients who need nonoral therapy. This dose ranging study unequivocally demonstrates the benefits of vazegepant in the acute treatment of migraine."

Vlad Coric, MD, chief executive officer of Biohaven, stated, "Biohaven has now advanced yet another CGRP signal-targeting product into the clinic highlighting the value of our migraine platform and the capability of the organization to develop products that meet patients' needs. This shows our ability to execute on clinical trials, now delivering our 4th  consecutive positive pivotal trial in migraine." Dr. Coric added, "We are excited to demonstrate the efficacy and tolerability of the 1st intranasal CGRP receptor antagonist for patients with migraine. These positive results, in a large, multiple arm phase 2/3 dose finding trial, may allow us to accelerate this program with only one additional positive efficacy trial likely needed for submission. Biohaven is grateful to the patients and investigators who have contributed to the success of the vazegepant and rimegepant programs."