The third generation, high-affinity, selective small molecule CGRP receptor antagonist was significantly superior in the 2 higher doses on both co-primary end points of pain freedom and most bothersome symptoms.
Richard B. Lipton, MD
Newly announced topline results from a phase 2/3 clinical trial suggest that intranasal vazegepant is significantly greater than placebo in the acute treatment of migraine in adult patients, according to its manufacturer, Biohaven Pharmaceuticals.
The third generation, high-affinity, selective small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist was assessed in doses of 5 mg (n = 387), 10 mg (n = 391) and 20 mg (n = 402) and compared to a placebo group (n = 401). The therapy separated from placebo statistically in the 2 higher doses on both co-primary end points of pain freedom and most bothersome symptoms.
Additional results from the study (NCT03872453) are anticipated to be presented at upcoming scientific meetings in 2020.
“A large number of patients need a non-oral, acute migraine treatment option, particularly those with prominent nausea, vomiting or gastroparesis,” Richard B. Lipton, MD, professor and vice-chair of neurology, and director, Montefiore Headache Center, Albert Einstein College of Medicine, said in a statement. “Most of my patients don't like needles. Vazegepant is the first CGRP receptor antagonist delivered in an intranasal formulation, a benefit for patients who need non-oral therapy. This dose-ranging study unequivocally demonstrates the benefits of vazegepant in the acute treatment of migraine."
The 10-mg and 20-mg groups experienced 22.5% (P = .0113) and 23.1% (P = .0055) reductions in pain freedom at 2 hours post-dose compared to 15.5% with placebo. The 5-mg group experienced a 19.6% reduction, though it was not significant (P = .1214).
With regard to freedom from most bothersome symptoms—photophobia, phonophobia, or nausea—at 2 hours, both the 10- and 20-mg groups showed significant differences from placebo. The placebo group reported a 33.7% reduction, compared to 41.9% with 10 mg (P = .0.155) and 42.5% with 20 mg (P = .0094).
All told, Biohaven noted that vazegepant’s benefits were deemed durable and sustained, without the need for rescue medication over 48 hours (P <.05), with sustained pain freedom through the 24-hour and 48-hour marks for all 3 doses. Similar results were seen for all 3 doses for sustained pain relief at 24 hours, and with the 5-mg and 10-mg doses at 48 hours.
"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,” Vlad Coric, MD, chief executive officer, Biohaven, said in a statement. “This shows our ability to execute on clinical trials, now delivering our 4th consecutive positive pivotal trial in migraine.”
Vazegepant also displayed superiority to placebo on multiple secondary end points which suggest early activity (nominal P <.05), including rapid onset with pain relief at 15 minutes for the 2 higher doses and a return to normal function as early as 30 minutes for the highest dose. Both higher doses—10 mg and 20 mg—of vazegepant displayed benefits on both pain relief and return to normal function 2 hours after administration.
"We are excited to demonstrate the efficacy and tolerability of the first intranasal CGRP receptor antagonist for patients with migraine,” Coric said. “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."
As for safety, the therapy was deemed overall well-tolerated, with upward of 80% of all adverse events (AEs) considered mild. The most common AEs were dysgeusia (vazegepant: range, 13.5% to 16.1%; placebo: 3.5%) and nasal discomfort (vazegepant: range, 1.3% to 5.2%; placebo: 0.2%). As well, there were no signals of hepatoxicity in any of the 3 treatment arms.
Biohaven Achieves Positive Topline Results in Pivotal Phase 2/3 Study of Vazegepant, the First and Only Intranasal CGRP Receptor Antagonist in Clinical Development for the Acute Treatment of Migraine [press release]. New Haven, CT: Biohaven Pharmaceuticals; Published December 17, 2019. biohavenpharma.com/investors/news-events/press-releases/12-17-2019. Accessed December 17, 2019.