Results from a 1-year, open-label safety study suggest that Patients who fall into this category may be ineligible for treatment with triptans.
Dr. Susan Hutchinson
There are mechanistic concerns with rimegepant and related CGRP receptor antagonists. They block CGRP’s effect in the central nervous system, but CGRP is also active in blood vessels and the heart, leading to the possibility that countering its vasodilating effect could expose organs to risk of ischemia.
The Food and Drug Administration approved rimegepant in 2020 for treatment of acute migraine attacks. Sponsor Biohaven is also seeking approval for migraine prevention after a successful phase 3 study published January 2021 in The Lancet.
Susan Hutchinson, MD, who is a headache specialist at Orange County Migraine & Headache Center in Irvine, Calif., presented the results at the American Academy of Neurology’s 2021 annual meeting. The open-label study suggested that rimegepant is generally safe. “The proportion of subjects reporting at least one adverse event was similar among subjects whether they had zero, one, or two or more cardiovascular disease risk factors, and also among those with low and moderate to high 10-year cardiovascular risk, as determined by the Framingham Risk Score,” said Dr. Hutchinson during her presentation.
Still, there was one concerning case: A 53-year-old man experienced an attack of angina. But he already had angina prior to the study, was being treated for hypercholesterolemia, and had current or former exposure to statins. “This adverse event was deemed by the investigator to not be related to rimegepant,” said Dr. Hutchinson.
During the following question-and-answer session, an attendee pressed Dr. Hutchinson about the case, and she admitted to some initial doubts. “That was my concern when I saw those slides. I’m like, ‘oh, my goodness.’ ” She clarified that the man’s angina history dated to 2016, which was several years before the trial, and the episode of angina occurred 7 months after the first dose of rimegepant. “He was treated with nitroglycerin and taken out of the trial,” said Dr. Hutchinson.
Proper patient selection is key
The research adds to the literature on rimegepant by providing data on multiple uses, as opposed to the phase 3 study, which only looked at single use, according to Olivia Begasse de Dhaem, MD, who is a neurology attending physician at Stamford (Conn.) Health and was the session moderator. Rimegepant and other oral CGRP receptor antagonists, including the FDA-approved ubrogepant and the investigative drug atogepant, will help fill the gap of patients who don’t tolerate or are ineligible for triptans, she said.
Dr. Begasse de Dhaem
Dr. Begasse de Dhaem pointed out that patient selection remains important. “I think the main thing for patient care is to look at whether the patient we are treating would fit within the inclusion criteria, or would have been excluded from this study,” said Dr. Begasse de Dhaem. Specifically, according to its clinicaltrials.gov page, the trial excluded patients with hemiplegic and basilar migraine, as well as patients with uncontrolled, unstable, or recently diagnosed cardiovascular disease, those with a body mass index of 30 kg/m2 or higher, and hemoglobin A1c levels of 6.5% or higher. “This also looked at people with less than 15 migraine days per month, so it’s limited in how much we can extrapolate to people with chronic migraine who may take more than 7.7 rimegepant [doses, the mean value taken by trial participants] per month,” Dr. Begasse de Dhaem added.
She also applauded the inclusion of older patients in the study, noting that most migraine studies have an upper age limit.
The study included subjects who experienced 2-14 moderate or severe migraine attacks per month, and they were allowed to take other migraine medications. Cardiovascular risk factors did not prevent entry to the trial and, like the previous pivotal trial, the long-term safety study admitted subjects older than 65. Among the study cohort, 1,514 participants were told to treat migraine pain of any intensity with 75 mg rimegepant up to once per day on an as-needed basis (PRN), and a second group of 286 were told to take 75 mg rimegepant every other day for 12 weeks, along with PRN dosing on nonscheduled treatment days.
Nearly 90% of subjects were female, the mean age was 43.1 years, and 3.7% were age 65 or older. Among the study participants, 40.8% had cardiovascular risk factors, including 28.8% with one risk factor, and 12.1% with two or more. About 7% had a moderate to high (≥10%) 10-year cardiovascular risk by Framingham Risk Score, 23.6% had a family history of coronary artery disease, 11.7% were being treated for hypertension, 10.4% smoked, 8.3% were being treated with a statin, and 3.0% had a history of diabetes.
In total, subjects were exposed to 112,014 doses of rimegepant, a mean of 7.7 doses per 4-week period. The exposure was similar across all risk groups, which included zero risk factors, one risk factor, and two or more risk factors; FRS of less than 10%; and FRS of 10% or greater. The most common adverse events were upper respiratory tract infection (8.8%), nasopharyngitis (6.8%), and sinusitis (5.1%). The frequency of one or more adverse events was similar among those with zero cardiovascular risk factors (59.6%), one risk factor (61.4%), two or more risk factors (62.2%), FRS less than 10% (59.9%), and FRS of 10% or greater (59.9%).
The study was funded by Biohaven Pharmaceuticals. Dr. Hutchinson has been a consultant or advisory board member for Biohaven, Alder, Allergan, Amgen, Avanir, electroCore, Lilly, Novartis, Promius, Supernus, and Teva. She has been on the speaker’s bureau for Allergan, Amgen, Avanir, electroCore, Lilly, Novartis, Promius, Supernus, and Teva. Dr. Begasse de Dhaem has no relevant financial disclosures.