A new phase 3 study shows the efficacy of rimegepant when compared with placebo in acute migraine treatment.
Richard B. Lipton, MD, with the Department of Neurology and Epidemiology and Population Health, Albert Einstein College of Medicine, and Montefiore Medical Center, New York, and colleagues reported their findings in the July 11, 2019 issue of The New England Journal of Medicine.
Migraine is a very common chronic headache disorder – it is estimated that up to one billion people worldwide suffer migraines. Since their introduction in the early 1990s, triptans have been the most commonly used prescription medication class for migraine therapy. They work by acting as serotonin (5-hydroxytryptamine [5-HT]) agonists with a strong affinity for the 5-HT1B and 5-HT1D receptors, which are associated with vasoconstriction and at least partial inhibition of the release of vasoactive peptides from trigeminal neurons. Many previous published studies have shown that triptans are highly effective, with 70-80% of patients reporting significant pain reduction within ninety minutes of one dose.
Although proven effective, triptans use has been limited by a large adverse side effect profile and many contraindications. They cannot be used in cardiac, cerebral, or peripheral vascular disease, severe hypertension, and Raynaud’s syndrome, due to their vasoconstrictive properties. Many patients report being unable to tolerate triptans because of side effects such as nausea, flushing, dizziness, malaise, chest tightness, tingling, taste disturbance, and headache recurrence.
A new class of migraine drugs, currently in development, are the small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists (gepants). CGRP levels correlate with the presence of migraine, and the gepants have been shown to be effective in migraine pain relief. Rimegepant, one such gepant, has been shown in a previous dose-ranging phase 2b study to be effective in treating migraine at the 75-mg dose. The gepants do not cause vasoconstriction, thus are free from the cardiovascular effects of the triptans.
This phase 3 trial was a multicenter, randomized, double-blind study, which enrolled 1186 adult migraine patients from 49 centers in the United States. 1072 of them were included in the modified intention-to-treat population. 537 patients were randomly assigned to receive rimegepant 75 mg, and 535 patients to receive placebo, for a single migraine attack of moderate or severe intensity. Pain intensity and the presence of associated symptoms were assessed and compared between groups.
Evaluated at two hours after the dose, 19.6% of the patients in the rimegepant group and 12.0% in the placebo group reported complete pain relief (between-group difference 7.6%; 95% confidence interval [CI] 3.3 to 11.9; P<0.001). Also, patient-reported relief from photophobia at two hours post-dose was 37.4% in the rimegepant group and 22.3% in the placebo group (P<0.001), relief from phonophobia was reported at 36.7% in the rimegepant group and 26.8% in the placebo group (P=0.004), and relief from the most bothersome symptom was 37.6% and 25.2%, respectively (P<0.001).
The most common adverse events were nausea (reported by 1.8% of the patients in the rimegepant group and 1.1% of the patients in the placebo group) and urinary tract infection (1.5% and 1.1%, respectively).
Although this study showed the efficacy of a single dose of rimegepant in acute migraine, Dr. Lipton and colleagues concluded that “larger and longer trials are needed to determine the consistency of response and the safety and effectiveness of the drug as compared with other migraine treatments.”
The study was funded by Biohaven Pharmaceuticals.
Lipton, RB, et al. Rimegepant, an Oral Calcitonin Gene-Related Peptide Receptor Antagonist, for Migraine. N Engl J Med. 2019; 381:142-49.