A post-hoc analysis of the phase 2/3 trial of rimegepant revealed early and sustained efficacy compared to placebo, with significant reductions in weekly migraine days.
Data from a recent study suggest that rimegepant (Nurtec ODT; Biohaven) achieves sustained migraine prevention within the first week of every other day dosing. These findings were presented at the 2021 Virtual American Headache Society (AHS) 63rd Annual Scientific Meeting, June 3-6, by Richard Lipton, MD, director, Montefiore Headache Center.
“The benefits of oral preventive treatments for migraine often develop slowly, over weeks to months, due in part to the requirements for dose titration. Rimegepant, an oral small molecule calcitonin gene-related peptide receptor antagonist, gepant, has demonstrated efficacy and safety in 3 phase 3 clinical trials in the acute treatment of migraine and in a phase 2/3 clinical trial for the preventive treatment of migraine,” Lipton and colleagues wrote.
The investigators performed a post-hoc analysis of the multicenter, randomized, double-blind, placebo-controlled phase 2/3 trial (NCT03732638) of rimegepant for the preventive treatment of migraine. The trial enrolled 747 participants, 373 randomized to rimegepant 75 mg and 374 to placebo for 12 weeks, 741 of which were treated (370, rimegepant; 371, placebo). Participants were randomized after a 4-week observation period. The participants had a mean age of 41.2 years, most were women (82.7%), most were white (81.5%), and 23.3% had a history of chronic migraine.
The trial previously showed that rimegepant, dosed every other day, was superior to placebo in mean change in monthly migraine days (MMD) during weeks 9 through 12—the primary end point—and during the first 4 weeks of the double-blind period—the secondary end point. This post-hoc analysis sought to assess the effect of rimegepant on weekly migraine days (WMD) over the first 4 weeks of treatment.
This post-hoc analysis demonstrated that rimegepant 75 mg (WMD change from observation period least-squares mean [LSM], –0.7 [standard error (SE), 0.08; 95% CI, –0.84 to –0.53]) was more effective than placebo (LSM, –0.3 [SE, 0.08; 95% CI, –0.45 to –0.13]) during week 1 (LSM difference, –0.4 [SE, 0.11; 95% CI, –0.61 to –0.18]; P = .0003). Within the first week of treatment, rimegepant-treated participants had a 30% reduction (95% CI, –36.1 to –23.9) in weekly migraine days compared with a 9.4% reduction (95% CI, –32.6 to –19.8) for placebo-treated participants.
Rimegepant continued to show more efficacy than placebo in the next few weeks of double-blind treatment. In week 2, WMD LSM change from observation for rimegepant 75 mg was –0.6 (SE, 0.08; 95% CI, –0.79 to –0.46) while placebo had an LSM of –0.2 (SE, 0.08; 95% CI, –0.39 to –0.07; LSM difference, –0.4 [SE, 0.11; 95% CI, –0.61 to –0.17]; P = .0005). Those treated with rimegepant had a 26.2% reduction (95% CI, –32.6 to –19.8) in WMDs while those treated with placebo had a 5.6% reduction (95% CI, –15.7 to 4.5).
In week 3, the rimegepant group had a WMD LSM change from observation of –0.8 (SE, 0.08; 95% CI, –0.97 to –0.65) while the placebo group had an LSM of –0.5 (SE, 0.08; 95% CI, –0.69 to –0.37; LSM difference, –0.3 [SE, -.11; 95% CI, –0.50 to –0.06]; P = .0111). The rimegepant group had a 35.1% reduction (95% CI, –40.9 to –29.2) in WMD while the placebo group had a 14.6% reduction (95% CI, –32.3 to 3.1).
In week 4, the differences were no longer significant, with the rimegepant group having a WMD LSM change from observation of –0.8 (SE, 0.08; 95% CI, –0.91 to –0.60) while the placebo group had an LSM of –0.6 (SE, 0.08; 95% CI, –0.75 to –0.44; LSM difference, –0.2 [SE, 0.11; 95% CI, –0.37 to 0.05]; P = .1275). The rimegepant group had a 33.2% reduction (95% CI, –38.9 to –27.4) in WMD while the placebo group had a 26.1% reduction in WMD (95% CI, –32.7 to –19.4).
“Oral rimegepant 75 mg taken every other day demonstrated preventive effects on migraine within the first week of treatment. These rapid onset preventive effects, along with previously demonstrated single dose efficacy as an acute treatment, suggest that rimegepant may provide a new approach to treat migraine in an adaptive way depending on an individual’s acute and/or preventive treatment needs,” Lipton and colleagues concluded.
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