Updates on migraine management with rimegepant

Migraine is a debilitating neurological condition that affects millions of people worldwide, causing intense headaches, sensory disturbances, and a significant decline in quality of life. Approximately one-third of patients encounter aura, which encompasses transient focal neurological disturbances that precede the attack. [Lancet 2017;390:1211-1259; Headache 2021;61:1021-1039]

Treatment for migraines typically involves a combination of acute and preventive strategies. Acute symptomatic treatment for attacks includes simple analgesics such as paracetamol or NSAIDs, and migraine-specific agents, such as triptans. Options for preventing migraines include medications conventionally used for other conditions, such as beta-blockers, antidepressants, and antiepileptic drugs. However, some of these options may have contraindications, interactions, limited-to-moderate efficacy, and notable adverse effects.

Rimegepant is a novel oral medication that can both treat and prevent migraine attacks. It works by inhibiting the calcitonin gene-related peptide (CGRP) receptor, targeting the root cause of migraine. Approved by Singapore’s Health Science Authority in February 2023, rimegepant is indicated for the acute treatment of migraine with or without aura in adults and for the prevention of episodic migraines in adults who experience at least four migraine attacks per month.

Rimegepant for acute treatment of migraine
Rimegepant stands out as a game-changer due to its ability to provide rapid and sustained relief from migraines. It is available as an orally disintegrating tablet (ODT) formulation, which was developed to improve patient convenience and response time. Rimegepant starts working within an hour after ingestion, with effects lasting up to 48 hours, minimizing the impact of migraine on daily activities and productivity. [CNS Drugs 2023;37:255-265]

In the double-blind, randomized, phase III Study 303, a single dose of rimegepant 75 mg ODT provided superior efficacy to placebo for the acute treatment of migraine. Twenty-one percent (142/669) of patients on rimegepant experienced freedom from pain at 2 hours post-dose compared with 11 percent (74/682) for placebo, and 35 percent (235/669) experienced freedom from their most bothersome symptom (light sensitivity, sound sensitivity, or nausea) at 2 hours post-dose compared with 27 percent (183/682) for placebo. These benefits were sustained through 48 hours for some patients (Figure 1). [Lancet 2019;394:737-745]

Rimegepant for prevention of migraine episodes
Study 305 was a pivotal phase III trial which assessed the efficacy of rimegepant for the preventive treatment of migraine. The trial consisted of a screening phase (including a 4-week observation period) and a 12-week double-blind treatment phase. Eligible patients were adults with at least a 1-year history of migraine. The primary efficacy endpoint was change from the 4-week observation period in the mean number of migraine days per month in the last 4 weeks of the double-blind treatment phase (weeks 9–12). [Lancet 2021;397:51-60]

Rimegepant rapidly and effectively prevented migraine, reducing migraine days by 30 percent after 1 week of every other day treatment. Rimegepant was superior to placebo on the primary endpoint of change in the mean number of migraine days per month during weeks 9–12 (Table 1). By 3 months of treatment, approximately half of patients experienced at least a 50-percent reduction in moderate-to-severe migraine days. [Lancet 2021;397:51-60]

Safety and tolerability of rimegepant
Importantly, rimegepant has demonstrated a favourable safety profile. The adverse event (AE) profile of rimegepant is comparable to placebo, with no evidence of hepatotoxicity or cardiovascular toxicity reported. [Lancet 2019;394:737-745; Lancet 2021;397:51-60]

Most AEs were mild or moderate in severity and resolved without treatment. In Study 303, the most common AEs were nausea and urinary tract infection. [Lancet 2019; 394:737-745] In study 305, in which rimegepant was given every other day, the most common AEs were nasopharyngitis, nausea, UTI, and upper respiratory tract infection. [Lancet 2021;397:51-60]