Migraine is a chronic neurological disease characterized by recurrent headaches, usually unilateral headaches, paroxysmal headaches, and accompanied by photophobia, panic, nausea and vomiting. More than 1 billion people worldwide suffer from migraines, and three-quarters of them are women. At present, the drug treatment of migraine is generally divided into two categories-acute treatment and preventive treatment. Acute treatment is used to relieve symptoms during the attack, and preventive medication reduces the frequency and severity of attacks. However, most traditional oral preventive treatments (such as β-blockers, antiepileptic drugs, and tricyclic antidepressants) are not specifically developed for migraine, and their safety and tolerability are generally poor. Patient compliance is also poor.
Recently, the team of Robert Croop of the American Biohaven pharmaceutical company published an article entitled "Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial" in The Lancet. The efficacy of oral remijipam in preventing migraine was studied.
Remejipam is an oral calcitonin gene-related peptide (CGRP) receptor antagonist that has been approved by the United States for the acute treatment of adult migraine. In multiple randomized, placebo-controlled clinical trials, the 75 mg dose of Remejipam is safe and effective. Currently, four monoclonal antibodies targeting CGRP receptors or ligands have been identified as preventive treatments for migraine. The purpose of this study was to compare the safety, tolerability and effectiveness of taking Remejipam every other day with placebo in preventing migraine.
The research team conducted a multi-center, randomized, double-blind, placebo-controlled trial in 92 research centers in the United States to evaluate the safety and effectiveness of remijipam in the prevention and treatment of migraine. The study consists of three phases, including a 4-week observation period, a 12-week double-blind treatment period, and a follow-up period. Eligible participants are men and women 18 years of age and older, with at least 1 year of migraine with aura, history of migraine without aura, or chronic migraine, and migraine for the first time before the age of 50. During the 3-month period before the screening visit, participants must also have at least 4 (not more than 18) moderate or severe migraine attacks.
From November 14, 2018 to August 30, 2019, the research team recruited 747 adults with a history of migraine for at least one year. After a 4-week observation period, the participants were randomly assigned, of which 373 received remijipam treatment, and 374 received matching placebo treatment, once every other day for 12 weeks. The primary efficacy endpoint was the change in the average number of migraine days per month during the last 4 weeks (9-12 weeks) compared to the 4-week observation period.
In the end, a total of 695 participants were included in the efficacy analysis, including 348 in the remijipam group and 347 in the placebo group. From 9 to 12 weeks, the remijipam group was better than the placebo group in the primary endpoint of the change in the average number of migraine days per month. Compared with the observation period, within 9-12 weeks, the average number of migraine days per month in the remijipam group decreased by 4.3 days, and the placebo group decreased by an average of 3.5 days. The difference was significant. 741 participants received the study drug and were included in the safety analysis.
Adverse events were reported in 133 (36%) of 370 patients in the remijipam group and 133 (36%) of 371 patients in the placebo group. Seven (2%) participants in the remijipam group and 4 (1%) participants in the placebo group discontinued the study due to adverse events, and no patients died during the period. Research results show that taking Remejipam every other day can effectively prevent migraine and is safe to tolerate.
Current preclinical studies have confirmed that long-term antagonism of the CGRP pathway has nothing to do with headaches caused by drug overuse. Therefore, the results of this study show the potential of Remejipam in the preventive treatment of migraine. The use of remijipam in the acute and preventive treatment of migraine may reduce the overall burden of migraine-related diseases.