New Drug
Cara Aldridge Young
On May 27, FDA expanded the indication for rimegepant (Nurtec ODT—Biohaven) to include preventive treatment in adults with episodic migraine, defined as fewer than 15 headache days per month. This new indication for rimegepant makes it the first oral calcitonin gene-related peptide (CGRP) receptor antagonist approved for preventive treatment of migraine and the only migraine medication approved as a dual therapy for acute and preventive treatment.
This is “one of the most groundbreaking things to happen to migraine treatment in my 40 years of practicing headache medicine,” said study investigator Peter J. Goadsby, MD, PhD, professor of neurology at the University of California, Los Angeles, and King’s College London, in a news release from the manufacturer, Biohaven. “To have one medication patients can use to treat and prevent migraine will likely change the treatment paradigm for many of the millions of people who live with migraine.”
Rimegepant was originally approved in 2020 for acute treatment of adult patients with migraine, with or without aura, regardless of the number of monthly migraine days (MMDs). Since approximately 95% of all U.S. migraine patients experience fewer than 15 headache days per month, the new indication significantly expands preventive treatment options for most people living with migraine, said Biohaven.
How it works, recommended dosage
The recommended dosage is 75 mg orally once daily as needed to stop migraine attacks or every other day to help prevent episodic migraine and reduce the number of MMDs. Rimegepant works by blocking the CGRP receptor, treating a root cause of migraine. A single 75-mg dose can deliver fast pain relief that lasts up to 48 hours for many patients, according to Biohaven.
Clinical trial highlights
Approval was based on a pivotal double-blind, randomized, placebo-controlled Phase II/III clinical trial for
preventive treatment of migraine. Results of the primary study endpoint—change from the observation period in MMDs during weeks 9 to 12—demonstrated that rimegepant was superior to placebo, decreasing MMDs by 4.3 days per month after 3 months of treatment (−4.3 vs. −3.5, P = 0.0099). Rimegepant preventive effects were seen as early as the first week of therapy.
Results of a key secondary endpoint—50% or greater reduction in mean number of moderate or severe MMDs during weeks 9 to 12 (49% vs. 41%, P = 0.0438)—showed that approximately half of patients treated with rimegepant had a 50% or greater reduction in the number of moderate to severe MMDs.
Adverse effects, contraindications
In clinical trials, rimegepant was generally well tolerated. The most common adverse effects were nausea (2.7% vs. 0.8% in placebo) and stomach pain/indigestion (2.4% vs. 0.8% in placebo).
Rimegepant is contraindicated in patients with a history of hypersensitivity to rimegepant or any of its components. Patients should not take rimegepant while they’re on strong CYP3A4 inhibitors and inhibitors of P-gp or BCRP. Patients on a moderate CYP3A4 inhibitor should avoid another dose of rimegepant within 48 hours. Patients with severe hepatic impairment should not take rimegepant, as exposures were significantly higher in clinical trial participants with severe hepatic impairment.
Patient counseling
Advise patients that they may take up to 18 doses per month for both acute and preventive therapy but should not take more than 75 mg in a 24-hour period. Inform patients that the safety of using more than 18 doses in a 30-day period has not been established. Instruct patients not to remove the blister from the outer aluminum pouch until they’re ready to take the tablet.
Educate patients about the signs and symptoms of hypersensitivity reactions and explain that these reactions can occur days after administration. Tell patients to contact their physician immediately if they have signs or symptoms of hypersensitivity reactions.
Caution women who are pregnant or considering pregnancy that no adequate data are available on use of rimegepant and fetal developmental risk. In the U.S. general population, the estimated background risk of major birth defects and miscarriage is 2% to 4% and 15% to 20%, respectively. The estimated rate of major birth defects (2.2%–2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine.
Published data have suggested that women with migraine may be at increased risk of preeclampsia and gestational hypertension during pregnancy.