QOD Rimegepant Shows Slight but Significant Reduction in Migraine Days

Richard B. Lipton, MD

A recent multicenter, phase 2/3, randomized, double-blind, placebo-controlled trial (NCT03732638) has shown that rimegepant is effective for preventing migraine when taken every other day (QOD) and is well-tolerated in patients with the headache disorder.

Patients on rimegepant experienced a greater reduction in migraine days per month when compared to those on placebo. During weeks 9–12, rimegepant patients had a –4.3-day (95% CI, –4.8 to –3.9) mean change in migraine days from the observation period during weeks 1–4. Patients on placebo had a –3.5-day (95% CI, –4.0 to –3.0) change in migraine days (least squares mean [LSM] difference, −0.8 days; 95% CI −1.46 to −0.20; P = .0099).¹

Study co-author Richard B. Lipton, MD, professor and vice chair of neurology, Albert Einstein College of Medicine, and director, Montefiore Headache Center, said in a statement that, "migraine is a prevalent and debilitating disease, affecting roughly 1 in 6 Americans, and many are not helped by current treatments. The results...demonstrate the significant clinical benefits of rimegepant for the preventive treatment of migraine. These data show the promise of a new approach to preventive treatment with an oral calcitonin gene-related peptide (CGRP) antagonist."²

Lipton and colleagues analyzed data from 741 patients that were 83% (n = 613) female with a mean age of 41.2 years (standard deviation [SD], 13.1). These patients were randomly allocated to either rimegepant (n = 370) or placebo (n = 371) to evaluate safety; 695 patients were analyzed for efficacy, 348 assigned to rimegepant and 347 assigned to placebo. 

READ MORE: Rimegepant Application for Migraine Prevention Accepted for Review

Around 49% (n = 171; 95% CI, 44–54) of patients on rimegepant had at least a 50% reduction in the mean number of moderate or severe migraine days per month in the last month of double-blind treatment as compared to 41% (n = 142; 95% CI, 36–47) of patients on placebo. Patients on rimegepant had an LSM change of –3.6 (95% CI, –4.0 to –3.2) mean number of total migraine days per month over the 3-month treatment period as compared to –2.7 (95% CI, –3.1 to –2.3; P = .0017). The 2 groups did not statistically differ with respect to the LSM days of rescue medication per month in the last month of the double-blind phase (P = .39)

"These data demonstrate the continued innovation in migraine treatment aimed at CGRP mechanisms. This is the first time an oral CGRP migraine treatment has shown dual efficacy in both the acute and preventive treatment of migraine. With this flexibility, these therapies are truly disruptive and change the treatment paradigm for people living with migraine," study co-author Peter J. Goadsby, MD, PhD, DSc, professor of neurology, King's College, London, and University of California, Los Angeles, said in a statement. 

Lipton and colleagues also performed a post-hoc analysis of participants with or without a history of chronic migraine which showed evidence of rimegepant efficacy in both subgroups with respect to the 50% responder rate and reduction in migraine days.

The incidence of adverse events (AEs) reported by patients were the same between both groups—133 patients (36% for both groups) from each group reported AEs. Some patients discontinued due to AEs, 7 (2%) that were receiving rimegepant and 4 (1%) receiving placebo. No patients died.

Lars Edvinsson, MD, PhD, president, International Headache Society, and professor, Lund University, was less enthused about the results of the study, writing in a related editorial that “the improvement relative to placebo associated with rimegepant on this endpoint—less than 1 monthly migraine day—is disappointing. When comparing the efficacy of rimegepant 75 mg every other day with that of currently approved and used monoclonal antibodies towards CGRP or the CGRP receptor, the effect of rimegepant is at the lower end of the reported range.”³ 

REFERENCES

1. Kroop R, Lipton RB, Kudrow D, et al. Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial. Lancet Neurol. Published online December 15, 2020. doi: 10.1016/S0140-6736(20)32544-7
2. Biohaven's rimegepant for preventive treatment of migraine published in The Lancet. News release. Biohaven Pharmaceuticals. December 16, 2020. Accessed December 17, 2020. https://www.biohavenpharma.com/investors/news-events/press-releases/12-16-2020
3. Edvinsson L. Oral rimegepant for migraine prevention. Lancet Neurol. Published December 15, 2020. doi: 10.1016/S0140-6736(20)32624-6