Rimegepant Safe, Well-Tolerated for Migraine When Used Every Other DayJune 15, 2022
Rimegepant (Nurtec), an oral small molecule calcitonin gene-related peptide (CGRP) receptor antagonist for acute and preventive migraine treatment, was safe and well tolerated when used every other day plus as needed for up to 1 year, an open-label extension showed.
Most participants (81.4%) took 16 or fewer tablets per month and no liver safety concerns emerged, reported Richard Lipton, MD, of Albert Einstein College of Medicine in the Bronx, New York, in a presentation at the American Headache Society annual meeting.
“This is the first and only clinical trial to assess a single CGRP-targeting medication dosed both as a preventive treatment for migraine and an acute treatment for migraine,” Lipton said.
In 2021, rimegepant became the first drug approved for both acute and preventive migraine treatment. Like other gepant drugs, rimegepant can partially pass the blood-brain barrier to stop a migraine headache in progress. Clinical trials of an earlier gepant, telcagepant, were terminated due to liver toxicity concerns.
In acute migraine, rimegepant’s safety and tolerability were established in three phase III trials and a 1-year open-label safety study. In migraine prevention, the efficacy and safety were established in a 12-week phase II/III randomized placebo-controlled trial.
For the new analysis, Lipton and colleagues evaluated participants in a 1-year open-label extension of the phase II/III migraine prevention study to assess the safety and tolerability of rimegepant 75 mg dosed every other day for migraine prevention and as needed for acute treatment on nonscheduled dosing days for 52 weeks.
Adults 18 and older with a history of four to 18 moderate to severe monthly migraine attacks were eligible. On nonscheduled dosing days, participants could take rimegepant 75 mg up to once per day as needed for acute migraine treatment. Safety assessments included adverse events and clinical laboratory test evaluations, including liver function tests.
Patients recorded rimegepant use and the occurrence and severity of migraine attacks in an electronic diary. In-person visits occurred at weeks 2, 4, and every 4 weeks thereafter through week 52 of the open-label extension phase.
Of 741 people treated in the phase II/III trial, 603 (302 in the rimegepant group and 301 with placebo) were treated in the open-label extension.
The open-label population had a mean age of 42.6 and a mean history of 7.9 monthly attacks; 82.3% were female. The most common on-treatment adverse events were upper respiratory tract infection (7.1%), nasopharyngitis (6.3%), and back pain (4.3%).
The rate of discontinuation due to adverse events was 2.8%. “This included four COVID-related discontinuations,” Lipton said. “Overall, lost-to-followup, noncompliance, and withdrawal rates were very low, just half a percent.”
Though serious adverse events occurred in 2.2% of participants, none were considered to be related to rimegepant. Two deaths — one due to aortic dissection related to Marfan syndrome and one due to sepsis — were also considered unrelated to rimegepant.
Aminotransferases at three or more times the upper limit of normal were seen in 3.4% of participants, none of whom had concurrent elevations in bilirubin greater than two times the upper limit of normal.
Every-other-day plus as-needed dosing was associated with a consistent reduction in monthly migraine days throughout the study. “There’s a pretty striking decline over the course of 52 weeks,” Lipton noted.
“Thirty tablets per month were available to patients,” he said. “They averaged only 14.6 tablets for a 4-week period, demonstrating that the need for as-needed dosing was modest.”
This study was sponsored by Biohaven Pharmaceuticals.
Lipton disclosed relationships with the NIH, Migraine Research Foundation, National Headache Foundation, Novartis, Alder, Allergan, Amgen, Autonomic Technologies, Avanir, Biohaven, Boston Scientific, CoLucid, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Novartis, Teva, and Vedanta. He holds stock or options in Biohaven Pharmaceuticals, Manistee, and Ctrl M.