Pooled Analysis Demonstrate Rimegepant’s Effectiveness as Acute Migraine Treatment

Stewart J. Tepper, MD

A pooled analysis of 4 randomized placebo-controlled trials highlighted the therapeutic benefits of rimegepant (Nurtec ODT; Pfizer) in treating acute migraine. All told, treatment with a single 75 mg dose of the FDA-approved, calcitonin gene-related peptide (CGRP) antagonist resulted in better outcomes on pain freedom, rescue medication use, sustained pain freedom, and return to normal function over placebo.¹

Presented at the 2024 Migraine Trust International Symposium (MTIS) meeting, held September 5-8 in London, England, the analysis featured 4 studies (NCT03235479, NCT03237845, NCT03461757, NCT04574362) comprising 2,439 patients who received rimegepant and 2456 on placebo. Led by Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth and director of the Dartmouth Headache Center at Dartmouth Health, the co-primary end points at 2 hours post-dose were pain freedom and freedom from the most bothersome symptom (MBS).

The studies featured adult patients who had at least a 1-year history of migraine, 2-8 migraine attacks of moderate or severe pain intensity per month, and attacks that lasted 4-72 hours if untreated. Secondary endpoints were pain relief at 2 hours post-dose, return to normal function at 2 hours postdose (among those with disability at migraine onset), use of rescue medication within 24 hours postdose, and sustained pain freedom from 2–24 and 2–48 hours post-dose.

In comparison with placebo, a higher proportion of patients on rimegepant 75 mg once daily experienced pain freedom 2 hours post-dose (20.0% vs 11.8%; P <.0001) and MBS freedom 2 hours post-dose (40.2% vs 29.2%; P <.0001). It showed a well tolerated safety profile as well, with nausea as the only adverse event (AE) reported in at least 1% of treated participants (rimegepant: 1.4%; placebo: 1.3%). Severe AEs occurred in 0.3% and 0.1% of participants in the rimegepant and placebo groups, respectively.

Rimegepant, a CGRP antagonist, outperformed placebo on several secondary outcomes, including pain relief at 2 hours post-dose (60.3% vs 45.1%; P <.0001), return to normal function at 2 hours post-dose (33.5% vs 21.1%; P <.0001), and rescue medication use within 24 hours post-dose (15.5% vs 28.9%; P <.0001). In addition, more patients on rimegepant had better sustained pain freedom from 2-24 hours post-dose (14.5% vs 7.1%; P <.0001) and sustained pain freedom from 2-48 hours post-dose (12.6% vs 6.4%; P <.0001). Overall, serious AEs occurred in 0.1% of participants in both groups; none were deemed to be related to study treatment.

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Rimegepant was originally approved for the acute treatment of migraine in February 2020 and had its label expanded in 2021 to include preventive treatment of the disease. At the time, it became the first oral CGRP antagonist approved for both acute and preventive migraine.²

Since its approval, rimegepant has been tested in several different clinical scenarios. In 2022, an open-label assessment of the treatment showed that it is safe and well tolerated with every-other-day dosing for up to 1 year. The placebo-controlled study featured 603 individuals with preventive migraine who were randomly assigned to rimegepant (n = 301) or placebo (n = 302). The patients took a mean of 14.6 rimegepant doses per month (SD, 2.45) with 81.4% of them using 16 or fewer rimegepant tablets per month.³

"One very striking thing is that in these studies, a month is 28 days. So, if someone was taking rimegepant exclusively as a preventive, that would be dosing it 14 times every 28 days. We found that when people had free access to rimegepant to use it on other days, they only took 14.6 tablets for the 4-week interval," study author Richard B. Lipton, MD, director of the Montefiore Headache Center, told NeurologyLive^® at the time. "The reason that's interesting is that it tells us when people have free access to rimegepant and they're using it preventively. They don't end up needing a whole lot of acute treatment because not only did they not take very much for major pain, but they didn't take very much of any other acute treatment."

That same year, a phase 1 study published in Breastfeeding Medicine revealed that rimegepant was safe for use in lactating women with migraine. The open-label, single-center study showed that excretion of the therapy into human milk was very low and the therapeutic was safe, with no clinically meaningful abnormalities were observed in maternal vital signs, laboratory values, hematology results, chemistry results, or urinarlysis parameters. In total, the trial featured 12 women aged 18-40 years who had a gestation of 37-42 weeks and uncomplicated delivery of a single healthy child at least 2 weeks and less than 6 months before rimegepant administration.⁴

REFERENCES
1. Tepper SJ, Pavlovic JM, Yu S, et al. Efficacy and safety of rimegepant 75 mg for acute treatment of migraine: a pooled analysis of 4 randomized, placebo-controlled trials. Presented at: 2024 Migraine Trust International Symposium (MTIS) meeting; September 5-8. London, England.
2. FDA Approves Biohaven's NURTEC® ODT (rimegepant) for Prevention: Now the First and Only Migraine Medication for both Acute and Preventive Treatment. News release. May 27, 2021. Accessed September 9, 2024. https://www.prnewswire.com/news-releases/fda-approves-biohavens-nurtec-odt-rimegepant-for-prevention-now-the-first-and-only-migraine-medication-for-both-acute-and-preventive-treatment-301301304.html
3. Lipton RB, Kudrow D, Smith TR, et al. Safety and tolerability of rimegepant every other day for preventive treatment of migraine plus as-needed for acute treatment of migraine: Results from a 52-week, open-label extension study. Presented at: AHS Annual Scientific Meeting; June 9-11, 2022; Denver, CO. IOR-09
4. Baker TE, Croop R, Kamen L, et al. Human milk and plasma pharmacokinetics of single-dose Rimegepant 75 mg in health lactating women. Published online March 16, 2022. doi:10.1089/bfm.2021.0250