Long-Term Rimegepant Use Safe for Migraine Prevention

TOPLINE:

The use of the calcitonin gene-related peptide (CGRP) antagonist rimegepant 75 mg for 52 weeks showed a favorable safety profile and sustained benefits for migraine prevention in a new open-label extension (OLE) study. The treatment was associated with a reduction in monthly migraine days (MMDs), as well as a low frequency of adverse events (AEs) and no significant hepatic safety concerns.

METHODOLOGY:

• The original phase 2/3 multicenter, randomized, double-blind, placebo-controlled trial included adult participants who had 4-18 moderate-to-severe migraine attacks per month.
• As reported previously, participants who received one tablet of rimegepant 75 mg every other calendar day for 12 weeks had significantly fewer MMDs than those who received matching placebo, meeting the primary endpoint.
• The treatment phase was then followed by a 52-week OLE period, where safety and tolerability were assessed through AE monitoring, vital signs assessments, physical examinations, ECGs, and laboratory tests, with special attention to hepatic-related AEs. All OLE participants received the active anti-CGRP.
• Exploratory outcomes during the extension period included the mean reduction in the number of MMDs and the proportion of participants achieving ≥ 50% and 100% reductions in the number of MMDs.

TAKEAWAY:

• Among 603 participants who entered the OLE period, 71% completed the study; 52% experienced at least one AE, with most deemed to be mild. Only 2% of participants reported serious AEs, none of which were related to the liver or to the study drug.
• Treatment-related AEs occurred in 15% of participants, leading to drug discontinuation in 3%. The most common AEs reported were constipation, upper respiratory tract infection, nausea, migraine, increased liver enzymes, and weight gain, although each occurred in ≤ 1% of participants.
• The hepatic safety profile was favorable, and liver-related AEs were rare.
• The mean number of MMDs decreased by 6.2 d/mo over the OLE period, with sustained and increasing treatment benefits being observed without a decrease in the effect. The proportion of participants achieving ≥ 50% and 100% reductions in the number of MMDs increased during the extension period.

IN PRACTICE:

“This trial found that participants who took rimegepant every other day and as needed (up to one 75 mg tablet a day) experienced a reduction in migraine days and experienced few side effects. Moreover, the treatment benefits of rimegepant increased over a 1-year period without losing effectiveness,” the investigators wrote.

SOURCE:

This study was led by David Kudrow, MD, California Medical Clinic for Headache, Santa Monica, California. It was published online on June 30 in Headache.

LIMITATIONS:

Key limitations included the exclusion of participants with extremely frequent headaches (> 18 headache days per month), which limited the generalizability of the findings. The requirement for a consistent ≥ 50% monthly reduction may have underestimated sustained efficacy, post-randomization dropouts may have skewed the OLE sample, the lack of an active comparator may have introduced bias, and participants’ awareness of receiving the drug may have affected reporting. Efficacy endpoints were also exploratory, so definitive conclusions on long-term effectiveness could not be drawn.

DISCLOSURES:

This study was funded by Biohaven Pharmaceuticals. Several investigators reported having financial or employment ties with the funder or other pharmaceutical companies. One investigator also reported being on the editorial board of journals, including Headache. Full details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.