A 75 mg orally dissolving tablet formulation of the calcitonin gene-related peptide receptor antagonist met both co-primary end points of freedom from the patient-indicated most bothersome symptom and freedom from pain at 2 hours.
Richard B. Lipton, MD
A 75-mg orally dissolving tablet (ODT) formulation of rimegepant (Zydis) showed rapid onset of pain relief after a single-dose for patients with acute migraines, according to findings from a phase 3 randomized study presented at the 2019 American Academy of Neurology Annual Meeting.
Freedom from pain at 2 hours posttreatment was achieved for 21.2% of patients in the ODT rimegepant arm compared with 10.9% of those in the placebo group (P <.0001). Moreover, the patient-reported most bothersome symptom (MBS) at 2 hours was significantly reduced in the rimegepant group (35.1% vs 26.8%; P = .0009).
"The 2 co-primary end points were freedom from pain 2 hours post-dosing—which the study hit on—and freedom from the patient-indicated most bothersome symptom, including nausea, photophobia, and phonophobia—and the study was also successful for that end point," said lead investigator Richard B. Lipton, MD, Department of Neurology, Albert Einstein College of Medicine. "There was a rapid onset of pain relief with a single dose, and it was safe too."
Rimegepant is an oral antagonist of the CGRP receptor. Biohaven Pharmaceuticals, the company developing rimegepant, is currently in discussions with the FDA for potential approval of the tablet formulation. Based on meetings with the FDA, the company announced in early March that the FDA is expected to accept a new drug application for the medication.
"Rimegepant has been proven to be an effective treatment in the tablet form in 2 large-scale phase 3 studies," said Lipton. "This study looks at an orally dissolving tablet, with a Tmax that is 2 hours shorter than the tablet, demonstrating a more rapid onset of action."
The study exploring the ODT formulation enrolled 1351 patients at a median age of 40.2 years. Six hundred sixty-nine patients received rimegepant and 682 got placebo. The majority of enrolled participants across both arms were female (84.9%), and the mean number of moderate to severe attacks per month was 4.6 (±1.79). The mean duration for an untreated attack for patients was 29.5 hours (±21.6), the rates of MBS reported were photophobia (57%), nausea (23.5%), and phonophobia (19.3%).
"Using a hierarchical, gate-keeper model for controlling statistical significance and multiple comparisons, there were 21 consecutive endpoints that were positive in comparison to placebo," Lipton said, while adding that pain relief was seen early and was sustained with the CGRP inhibitor.
Pain relief was achieved at 60 minutes for 36.8% of patients in the ODT arm compared with 31.2% in the placebo group (P = 0.314). At 90 minutes, half of the patients in the rimegepant arm experienced pain relief (49.6%) compared with 37.2% in the placebo arm (P <.0001). Pain relief at 2 hours was 59.3% versus 43.3%, for rimegepant and placebo, respectively (P <.0001).
Sustained pain relief was achieved for 47.8% and 27.7% of patients for 2-24 hours and for 42.2% and 25.2% for 2-48 hours, in the rimegepant and placebo groups, respectively (P <.0001). Sustained freedom from MBS was achieved for 27.1% and 17.7% for 2-24 hours and for 23.2% and 16.4% for 2-48 hours, for rimegepant and placebo groups, respectively (P <.01)
The ability to function normally returned for 38.1% of patients at 2 hours in the rimegepant arm compared with 25.8% in the placebo group. Moreover, there was a lower probability of requiring rescue medications in the rimegepant arm compared with placebo (14.2% vs 29.2%).
The most common adverse events (AEs) with rimegepant were nausea and urinary tract infection, each of which occurred in ≤1.6% of patients. There were no treatment-related increases in transaminase greater than 3 times the upper limit of normal (ULN), Lipton noted. Treatment-related AEs occurred in 6.9% of patients in the rimegepant arm compared with 5.2% in the placebo group. There were no serious AEs in either group.
"The tolerability and safety profiles were similar to placebo. There was 1 patient in each group with a transaminase above the ULN, and neither was assessed to be related to study medication," said Lipton.
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Lipton RB, Coric V, Stock EG, et al. Efficacy, Safety, and Tolerability of Rimegepant 75 mg Orally Dissolving Tablet for the Acute Treatment of Migraine: A Phase 3 Double-Blind, Randomized, Placebo-Controlled Trial (Study 303). Presented at: 2019 American Academy of Neurology Annual Meeting. May 4-10, 2019; Philadelphia, PA. Poster 075.