Evaluate the efficacy and safety of rimegepant for preventive treatment of migraine.

Rimegepant is an oral small molecule CGRP receptor antagonist with demonstrated efficacy in 3 Phase 3 clinical trials for acute treatment of migraine. This was the first randomized placebo-controlled trial evaluating rimegepant for preventive treatment of migraine.

This multicenter, randomized, double-blind, placebo-controlled trial (NCT03732638) enrolled adults with a history of 4-18 monthly migraine attacks of moderate to severe pain intensity. After a 4-week observation period, eligible subjects were randomized to oral rimegepant 75 mg or placebo every other day for 12 weeks.

In total, 747 subjects were randomized (rimegepant n=373, placebo n=374); 741 were treated (rimegepant n=370, placebo n=371; mean age 41.2 years, 82.7% female, 81.5% white); and 695 were evaluated for efficacy (rimegepant n=348, placebo n=347). Rimegepant was superior to placebo on the primary endpoint of change from the observation period in mean monthly migraine days during Weeks 9-12 (−4.3 vs −3.5, P=0.0099). Rimegepant was also superior on the secondary endpoint of ≥50% reduction in mean number of moderate or severe monthly migraine days during Weeks 9-12 (49.1% vs 41.5%, P=0.0438). The incidence of adverse events (AEs) was similar in the rimegepant and placebo groups (35.9% vs 35.8%). The most common AEs in rimegepant or placebo-treated subjects, respectively, were nasopharyngitis (3.5% vs 2.4%); nausea (2.7% vs 0.8%); urinary tract infection (2.4% vs 2.2%); and upper respiratory tract infection (2.2% vs 2.7%). Four (1.1%) rimegepant-treated and 2 (0.5%) placebo-treated subjects had transaminases >3x the upper limit of normal.

Oral rimegepant taken every other day was effective for the preventive treatment of migraine with tolerability similar to placebo. In addition to its proven efficacy as an acute therapy for migraine, rimegepant may provide a unified approach to migraine as a single drug with both acute and preventive treatment attributes.