New study unlocks rimegepant benefits for acute migraine
A landmark study conducted in China and South Korea has demonstrated the effectiveness and safety of rimegepant – a groundbreaking orally administered calcitonin gene-related peptide (CGRP) antagonist – for the acute treatment of migraine among adults. [Lancet Neurol 2023;22:476-484] This phase III, double-blind, randomized, placebo-controlled trial marks the first clinical study of a gepant for migraine in China and South Korea, offering promising insights into migraine management.
Global burden and unmet needs in migraine
Migraine is a prevalent neurological condition affecting over 1.1 billion people globally and can result in severe headaches, nausea, and sensitivity to light and sound. [Lancet 2020;396:1204-1222; Cephalalgia 2018;38:1-211]. In China, 9.3 percent of adults (approximately 151.6 million) and 5.2 percent in South Korea (approximately 2.7 million) suffer from migraines. [J Headache Pain 2019;20:102; J Clin Neurol 2021;17:77-85]
Migraines adversely impact daily life, causing decreased academic and work performance and affecting social activities. [J Headache Pain 2019;20:102; J Clin Neurol 2021;17:77-85]
Current treatment for migraine in China and South Korea includes paracetamol, NSAIDs, ergot alkaloids, triptans, as well as herbal and traditional remedies. [Pain Medicine 2014;15:320-328; Korean J Clin Pharm 2021;31:35-43] Despite available treatments, at least 40 percent of people in both countries express dissatisfaction with their current migraine medications. [J Headache Pain 2021;22:45; Pain Medicine 2014;15:320-328]
In recent years, a substantial body of evidence has highlighted the significance of CGRP in migraine pathogenesis. CGRP levels rise during migraine attacks and decrease with treatment. This discovery led to the development of targeted anti-CGRP therapies, such as rimegepant orally disintegrating tablet for the acute treatment and prevention of migraine, offering high specificity and excellent tolerability. [Lancet 2019;394(10200):737-745]
Key findings illuminate rimegepant potential
The latest rimegepant study was conducted in 73 and 13 sites in China and South Korea, respectively, covering 86 outpatient clinics within hospitals and academic medical centres. The study sought to evaluate the efficacy and safety of rimegepant 75 mg compared with a placebo in treating single migraine episode of moderate-to-severe pain intensity. [Lancet Neurol 2023;22:476-484]
The trial enrolled adults 18 years and older with a history of migraine for at least a year, experiencing two to eight moderate-or-severe attacks monthly, with fewer than 15 headache days per month in the 3 months leading to the screening. Participants were stratified by use or non-use of preventive medication and by country (China or South Korea).
Of the 1,431 participants enrolled in the trial, 716 were administered rimegepant, and an equal number received placebo – 93 percent in the rimegepant group and 94 percent in the placebo group completed the treatment. The modified intention-to-treat (mITT) analysis, comprising 1,340 participants, revealed compelling results.
Freedom from pain and most bothersome symptoms
Two hours post-dosing, rimegepant demonstrated superiority over placebo. Among the rimegepant recipients, 20 percent experienced freedom from pain, which was significantly more compared with 11 percent in the placebo group (p<0.0001).
Additionally, rimegepant provided freedom from the most bothersome symptoms (nausea, phonophobia, or photophobia) for 50 percent of the participants, outshining the 36 percent achieved with placebo (p<0.0001) (Figure 1). [Lancet Neurol 2023;22:476-484]
Sustained pain freedom up to 48 hours and other outcomes
In addition, rimegepant outperformed placebo in all five key secondary endpoints, including sustained pain freedom for up to 48 hours (p<0.0001 for all outcomes) (Figure 2). [Lancet Neurol 2023; 22:476-484]
Importantly, the study underlined the safety and tolerability of rimegepant. Most adverse events were mild or moderate, unrelated to the study drug, and resolved without treatment. Additionally, there was no signal for drug-induced liver injury nor clinically meaningful changes in vital signs, ECG, or physical examination results. There were no serious adverse events related to rimegepant, underscoring its safety for acute migraine treatment.
What this means for patients
The findings offer hope for adults grappling with migraines in China and South Korea. Administration of a single 75 mg dose of rimegepant not only proved effective for treating acute migraine but also demonstrated safety similar to placebo. These results position rimegepant as a potential game-changer for migraine management in both countries.
New evidence also showed that rimegepant might be useful for patients with inadequate response or contraindication to triptans and other currently used agents. [Cephalalgia 2023;43:3331024221141686] Rimegepant could also potentially reduce the use of opioids for migraine, which is common in China and South Korea, but is not recommended by guidelines. [Lancet Neurol 2023;22:476-484]
While the results are highly encouraging, the investigators called for more research to support the long-term efficacy and safety of rimegepant, coupled with comparative studies against other migraine medications for adults. [Lancet Neurol 2023;22:476-84]