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Rimegepant appears safe, effective in acute migraine treatment

SAN FRANCISCO — Rimegepant – a small molecule calcitonin gene-related peptide receptor antagonist – induced favorable responses and appeared safe in patients with acute migraine, according to phase 3 study results presented at the American Headache Society Annual Scientific Meeting.

“The big news in acute treatment of migraine since the early ‘90s has been the class of triptans,” Richard B. Lipton, MD, professor and vice chair of neurology and director of the Montefiore Headache Center at the Albert Einstein College of Medicine, told Healio Internal Medicine. “There’s seven FDA-approved triptans in the U.S. and they are available as tablets, nasal sprays and injectables and they’ve certainly made a big difference for migraine patients.”

However, as Lipton noted, there are several unmet medical needs with the use of medications in the triptan class.

Approximately 34% of patients have been shown to not respond to triptans, according to Lipton.

Additionally, the class of triptans are contraindicated in people who have cardiovascular conditions, have experienced cardiovascular events or have undergone cardiovascular procedures. In addition, approximately 30%- to-40% of patients taking triptans have an attack recurrence.

“Most migraine medications, and this is certainly true for the triptans, if a patient takes them too often, they can make headaches worse on a long-term basis,” Lipton said. “We wanted to focus on those three areas of unmet need and wanted to identify an acute treatment that would be safe to use in patients with cardiovascular issues that would be a mechanistical alternative to triptans for people who didn’t respond to them. And a pipe dream was, we wanted a drug that would not cause medication-overuse headache. The hope was that rimegepant [Biohaven Pharmaceutical] would fill all three of those needs.”

Lipton and colleagues conducted a double-blind, randomized, placebo-controlled, multi-center phase 3 study of 1,072 patients (median age, 40.6 years; 88.7% female) to assess the efficacy and safety of rimegepant 75 mg. The study group comprised 537 patients, the placebo group included 535.

Patients had to be aged 18 years and have at least a 1-year history of migraine. Patients also had to experience two- to-eight migraine attacks of moderate or severe intensity per month and have had less than 15 days with headache per month (migraine or non-migraine) over the last 3 months.

Freedom of pain at 2 hours from baseline and freedom from what the patient designated as their most bothersome symptom served as the co-primary endpoints.

Some of the secondary and exploratory endpoints included the use of rescue medication within 24 hours and a sustained ability to function normally up to 48 hours after treatment.

More than half of the patients in both the rimegepant (58.8%) and placebo (56.6%) cohorts reported photophobia as their most bothersome symptom.

Rimegepant induced pain freedom at 2 hours post dose in 19.6% of patients compared with 12% of patients who received placebo (P = .0006).

Patients who received rimegepant also reported higher freedom of most bothersome symptom at 2 hours post dose (37.6% vs. 25.2%; P < .0001).

Thirty-seven percent of patients who received placebo reported using a rescue medication within 24 hours, whereas 21% of patients who received rimegepant reported rescue medication use within 24 hours (P < .0001).

The safety profile was similar in both cohorts; 17.1% of patients who received rimegepant reported an adverse event and 14.2% of those who received placebo reported an adverse event.

Nausea (n = 10) and urinary tract infection (n = 8) were reported to be the most common adverse events in patients who received rimegepant. No patients stopped treatment because of adverse events.

Lipton said that the results are promising and that he sees rimegepant as a treatment of first choice for individuals with cardiovascular contraindications to triptans.

“Estimates are that there are nearly 40 million Americans with migraine and 3.5 million who have absolute or relative contraindications to triptans,” he said. “For those people, if they have disabling migraine, rimegepant is likely to be a treatment of first choice.”

Lipton said he also sees the treatment being a second-choice option for patients when triptans stop working or triptans cause serious side effects.

“Rimegepant was studied as an acute treatment, but it’s possible that it will work as a preventive treatment,” Lipton said. “For what it’s worth, when people think CGRP-targeted therapies, it’s important to distinguish small molecular treatments from antibodies that are being developed for prevention. Because the erenumab [Aimovig; Novartis, Amgen] launch is generating so much attention in multiple spheres, painting that contrast is important.” – by Ryan McDonald

Reference:

Lipton RB, et al. IOR-02LB. Presented at: American Headache Society Annual Scientific Meeting; June 28-July 1, 2018; San Francisco.

Disclosures: Lipton reports receiving research grants from Allergan, Amgen, Dr. Reddy’s Laboratories and Novartis; consultancy, advisory board, or honoraria with Alder, Allergan, Amgen, Autonomic Technologies, Avanir, Boston Scientific, CoLucid, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Novartis, Teva and Vedanta; stock options in Biohaven Pharmaceuticals and eNeura Therapeutics.