Almost 20% of rimegepant-treated patients experienced pain freedom within 2 hours of receiving a 75-mg dose compared to the placebo group, in which 12% were pain-free at 2 hours.
Richard B. Lipton, MD
In a multicenter, phase 3 clinical trial, rimegepant (Zydis, Biohaven Pharmaceuticals) tablets proved superior to placebo for patients with migraine in acute settings. Treatment with the calcitonin-gene related peptide (CGRP) receptor antagonist ultimately resulted in a higher percentage of patients who were pain-free and free of their most bothersome symptom.1
All told, 19.6% of rimegepant-treated patients (n = 537) experienced pain freedom within 2 hours of receiving a 75-mg dose compared to the placebo group (n = 535), in which 12% were pain-free at 2 hours.
“This trial showed that among patients with migraine, treatment of an attack with rimegepant, which acts through inhibition of the CGRP receptor, resulted in a moderately higher percentage of patients who were free from pain and free from their most bothersome symptom 2 hours after the dose than placebo,” the investigators, led by Richard B. Lipton, MD, Department of Neurology, Albert Einstein College of Medicine, wrote.
Lipton and colleagues noted that in order to determine the consistency of response, as well as the safety and effectiveness compared to other available agents, lengthier and larger trials still needed. In total, this trial included 1186 patients, of which 594 patients were randomized to the rimegepant group and 592 patients to the placebo group.
In total, the rimegepant group was averaging 4.5±1.9 attacks per month lasting an average of 32.0±21.7 hours. The placebo group averaged 4.6±1.8 attacks per month lasting an average of 32.9±21.7 hours.
The absolute difference between the groups in pain-freedom was 7.6 percentage points (95% CI, 3.3-11.9; P <.001). The percentage of patients who were free from their most bothersome symptom 2 hours post-dose was 37.6% in the rimegepant group and 25.2% in the placebo group (absolute difference, 12.4 percentage points; 95% CI, 6.9-17.9; P <.001).
The most bothersome symptoms in the rimegepant and placebo groups were photophobia (rimegepant: 51.6%; n = 277; placebo: 52.1%; n = 279), nausea (rimegepant: 31.5%; n = 169; placebo: 27.7%; n = 148), and phonophobia (rimegepant: 13.4%; n = 72; placebo: 17.2%; n = 92).
With regard to individual secondary end points, Lipton et al. found that 37.4% (183 of 489) of patients in the rimegepant group experienced freedom from photophobia 2 hours after the dose compared to 22.3% (106 of 477) of patients in the placebo group, for an absolute difference of 15.1 points (95% CI, 9.4-20.8; P <.001). Likewise, freedom from phonophobia 2 hours post-dose was experienced by 36.7% (133 of 362) and 26.8% (100 of 374) of the rimegepant and placebo patients, respectively (absolute difference, 9.9; 95% CI, 3.2-16.6; P = .004). Pain relief 2 hours post-dose was achieved by 58.1% (n = 312) and 42.8% (n = 229) of rimegepant and placebo patients, respectively. The absolute difference was 15.3 points (95% CI, 9.4-21.2; P <.001).
The most common adverse events (AEs) were nausea—experienced by 1.8% (n = 10) of rimegepant and 1.1% (n = 6) of placebo patients—and urinary tract infection—experienced by 1.5% (n = 8) of rimegepant and 1.1% (n = 6) of placebo patients. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above the upper limit of normal range in 2.4% (n = 13) and 2.2% (n = 12) of rimegepant and placebo patients, respectively.
All told, 17.1% (n = 93) of rimegepant patients and 4.2% (n = 77) of placebo patients experienced any AE.
Lipton and colleagues identified a number of limitations. “First, the trial did not include an active comparator to rimegepant. Second, although the rimegepant and placebo groups were balanced with respect to baseline characteristics and features of the treated migraine attack immediately before administration of the dose, the single-attack design (i.e., assessment of treatment effect on a single episode of a condition) does not permit assessment of the consistency of the effects of the drug from attack to attack over time in the same patient. Third, although no evidence of adverse cardiac effects was observed, the trial population was not enriched for patients with cardiovascular disease,” they wrote.
Recently, Biohaven finalized the purchase of a priority review voucher to use alongside its New Drug Application for rimegepant orally dissolving tablet (ODT). At the time, Biohaven CEO Vlad Coric, MD, said in a statement that “we are excited about the potential of bringing rimegepant Zydis ODT to patients as quickly as possible.”2
As well, a recent presentation at the 2019 American Academy of Neurology Annual Meeting showed that the 75-mg ODT formulation of rimegepant provided rapid onset of pain relief after a single-dose for patients with acute migraines. 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).3
1. Lipton RB, Croop R, Stock EG, et al. Rimegepant, an oral calcitonin gene-related peptide receptor antagonist, for migraine. N Engl J Med. 2019;381:142-9. doi: 10.1056/NEJMoa1811090.
2. Biohaven secures Priority Review Voucher (prv) to expedite regulatory review of Rimegepant Zydis ODT new drug application [news release]. New Haven, Conn: Biohaven Pharmaceuticals; March 18, 2019. biohavenpharma.com/investors/news-events/press-releases/03-18-2019. Accessed July 9, 2019.
3. 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.