Rimegepant Is Well-Tolerated and Safe for Migraine Over 1 Year With Every-Other-Day Dosing

Patients in the open-label extension also showed limited need for acute treatment with rimegepant (Nurtec ODT; Biohaven Pharmaceuticals), as more than 80% of patients took 16 or fewer total tablets over the 28-day period.

Data from an open-label assessment of rimegepant (Nurtec ODT; Biohaven Pharmaceuticals) 75 mg dosed every other day for the preventive treatment of migraine—plus as-needed dosing on nonscheduled dosing days for acute treatment—was safe and well-tolerated without liver safety concerns for up to 1 year. Additionally, the use of as-needed acute treatment was limited, with a wide majority of patients taking 16 or fewer tablets each month.1

Presented at the 2022 American Headache Society (AHS) Annual Scientific Meeting, June 9-11, in Denver, Colorado, by Richard B. Lipton, MD, the data included 603 individuals who continued to the open-label phase from the double-blind period of this assessment (NCT03732638). All told, the rate of discontinuation because of adverse events (AEs) in the extension was 2.8%, with the most common on-treatment AEs being upper respiratory tract infection (7.1%), nasopharyngitis (6.3%), and back pain (4.3%).

Of the 603 individuals included, 301 were originally randomly assigned to rimegepant, and 302 to placebo. The open-label population had a mean age of 42.6 years (SD, 13.10) and a mean migraine history of 7.9 monthly attacks (SD, 2.74). Of the 603 individuals included, 82.7% were women. 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.

“We really wanted to address two questions. The first was, is it safe to give rimegepant in these doses; and the second was, is it effective to give rimegepant both as an acute and as a preventative treatment to the same patients,” Lipton, the Edwin S. Lowe Chair in Neurology, vice-chair, Saul R. Korey Department of Neurology, and director, Montefiore Headache Center, told NeurologyLive®. “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.”

“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,” Lipton added.

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Serious AEs were reported by 2.2% of those included, though none were deemed treatment related. Two deaths occurred (0.3%), 1 due to aortic dissection related to Marfan syndrome and 1 due to sepsis—also deemed unrelated to rimegepant treatment. Aminotransferases greater than 3 times the upper limit of normal (ULN) occurred in 3.4% of individuals, but none of them experienced concurrent elevations in bilirubin greater than 2 times ULN.

“The other thing that was very striking is that over the course of more than a year of treatment with rimegepant, monthly headache days continued to decline,” Lipton said, explaining that in the double-blind phase of the study there were statistically significant differences between rimegepant and placebo. “When people were crossed over from the placebo arm to the every-other-day rimegepant arm, the placebo group caught up with the rimegepant group after just 4 weeks of treatment. Then, there was a very steady reduction over the course of the next year in change from monthly headache days from baseline. Overall, there was a 7-day reduction in monthly headache days from baseline over the course of the year, which was a pretty striking effect.”

Those eligible for the trial needed to be aged 18 years or older with a history of 4 to 18 moderate to severe monthly migraine attacks. Those who completed 12 weeks of double-blind treatment with 75-mg rimegepant or placebo could continue with rimegepant for 52 weeks. On nonscheduled dosing days, individuals included were allowed to administer rimegepant up to once daily as needed and were asked to record the occurrence and severity of migraine attacks, as well as the use of treatment, in an electronic diary. Lipton et al noted that in-person visits occurred at weeks 2 and 4, and then every 4 weeks thereafter through week 52 of the open-label extension phase.

“The bottom line here is that this study shows that in open-label, naturalistic, real-world sorts of settings, when people are given the opportunity to use rimegepant both as a preventive and as an acute treatment, they do it. They don't take rimegepant very often, even when the drug is freely available, and the safety and tolerability and long-term, open-label efficacy data are very encouraging,” Lipton said.

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REFERENCE
1. 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