Orally dissolving rimegepant confers rapid, sustained relief for migraine pain
The small-molecule CGRP* receptor inhibitor rimegepant in orally disintegrating tablet (ODT) formulation provides rapid and sustained relief from an acute migraine attack with no safety concerns compared with placebo, according to a study presented at the recent AHS 2019 Meeting.
“Unique among drugs in the gepant class, rimegepant has shown efficacy as soon as 60 minutes and as long as 48 hours after a single dose,” the investigators reported.
“An ODT of rimegepant was developed … with the intention of optimizing its absorption rate and allowing administration without liquids, which might be of clinical importance to patients with migraine who experience nausea and vomiting,” they explained.
The double-blind, multicentre, phase III trial randomized 1,351 participants (mean age 40.2 years, 85 percent female) with at least 1-year history of migraine to treatment with rimegepant ODT 75 mg or placebo for a single migraine episode with moderate or severe pain intensity. [AHS 2019, abstract IOR05; Lancet 2019;doi:10.1016/S0140-6736(19)31606-X]
Significantly more patients treated with rimegepant ODT were free from pain 2 hours after dosing — the primary endpoint — compared with placebo (21 percent vs 11 percent; p<0.0001), thus meeting the prespecified criteria for superiority.
Rimegepant ODT was also superior for the coprimary endpoint of freedom from the most bothersome symptom at 2 hours after dosing (35 percent vs 27 percent; p=0.0009).
“Along with freedom from pain, rapid pain relief is among the most highly valued attributes of acute treatment,” the investigators pointed out.
Prespecified secondary endpoints such as pain relief and freedom from disability at 1 hour postdose, and sustained pain relief, freedom from disability, and freedom from most bothersome symptom from 2–48 hours after treatment were significantly improved with rimegepant ODT over placebo.
“It is possible that the ODT formulation, with its fast absorption and time to peak plasma concentration, was a factor in the relatively rapid onset of relief seen among participants,” suggested the investigators. “It is also possible that the relatively long half-life of rimegepant (10–12 hours) played a role in the sustained benefits observed through to 48 hours.”
In terms of safety and tolerability, the investigators reported that the profile was similar to placebo, with no sign of liver safety issues. Nausea (2 percent vs <1 percent) and urinary tract infection (1 percent vs 1 percent) were the most common adverse events reported. While one case of transaminase concentration >3× ULN** occurred in each treatment group, neither was considered related to the study medication. There were no reports of serious adverse events.
Nonetheless, the single-attack design of the current study, which assessed treatment effect on only a single migraine episode, precludes the assessment of the response consistency over time from attack to attack in the same patient. The lack of an active comparator is also a study limitation.
“Future clinical trials should establish the benefits of rimegepant across multiple attacks and identify patient groups most likely to respond to the ODT formulation,” said the investigators.
“In addition, the benefits of rimegepant in migraine subpopulations with the greatest unmet treatment needs, including those with cardiovascular contraindications or lack of response to triptans, should be studied, and long-term safety should be assessed,” they added.