Rimegepant 75 mgN=1089n (%)

PlaceboN=1089n (%)

≥1 AE 121 (11.1) 95 (8.7)Nausea 15 (1.4) 11 (1.0)Urinary tract infection 6 (.6) 5 (.5)

Serious AEs 3 (.3)a 3 (.3)AE, adverse eventaTwo subjects had not been dosed before the onset of the SAEs; 1 subject had low back pain, not drug-related, as determined by the investigator

• Nonsteroidal anti-inflammatory drugs (NSAIDs) and caffeinated analgesics available over-the-counter (OTC) are widely used for the acute treatment of migraine attacks

• The clinical benefits of these OTC agents can be inadequate for more severe pain and associated symptoms, and they have the potential to cause cardiovascular and gastrointestinal safety issues, as well as medication overuse headache

• Rimegepant is an orally administered small molecule calcitonin gene-related peptide receptor antagonist that has demonstrated efficacy and safety in the acute treatment of migraine in 3 separate Phase 3 clinical trials — 2 using an oral tablet1,2 and 1 with a novel orally disintegrating tablet (ODT) utilizing the Zydis® fast-dissolve technology3; rimegepant ODT demonstrated statistically significant pain relief and return to normal function at 60 minutes and through 48 hours postdose

• The objective of this post hoc analysis was to compare the efficacy of rimegepant and OTC NSAIDs for the acute treatment of migraine

Objective

• Two double-blind, randomized, placebo-controlled, multicenter trials of identical design were conducted utilizing an oral tablet (Study 301, NCT03235479; Study 302, NCT03237845), as shown in Figure 1

Methods

Figure 1. Study Design

• Aged ≥18 years, with ≥1-year history of ICHD-3 beta migraine• Two to 8 moderate or severe monthly migraine attacks; <15 monthly headache days (migraine or

nonmigraine) over the last 3 months• Preventive migraine medication dose stable for ≥3 months (if using)

Subjects

• Efficacy: time to first report of pain freedom and time to first report of pain relief; pain intensity was recorded just prior to treatment and at .25, .5, .75, 1, 2, 3, 4, 6, 8, 24, and 48 hours postdose

• Safety: AEs, ECGs, vital signs, physical measurements, routine laboratory tests, including liver function tests

Assessments

• Subjects who took a single dose of rimegepant 75 mg were compared with subjects initially randomized to placebo who used acetaminophen/aspirin/caffeine (AAC), ibuprofen, or any NSAID as rescue medication

• Kaplan-Meier curves were used to compare the efficacy endpoints of time to first report of pain freedom and time to first report of pain relief

• The time to event was calculated from the dose of rimegepant (for rimegepant) or the first dose of rescue medication (for AAC, ibuprofen, and any NSAID)

Statistical Analysis

Introduction

Conclusions•These analyses of data from 2 Phase 3 clinical trials show that rimegepant 75 mg was more effective than acetaminophen/caffeine/aspirin, ibuprofen, and other NSAIDs, as measured by time to first report of pain freedom and time to first report of pain relief

•Tolerability and safety were similar to placebo

• Rimegepant was well tolerated, as shown in Table 2• The most common AEs were nausea and urinary tract infection (≤1.4%)• No serious treatment-related AEs were reported• No liver safety concerns were identified

Safety

Table 2. On-Treatment Adverse Events With Rimegepant and Placebo

Figure 7. Time to First Report of Pain Freedom: Rimegepant Versus All OTCs

Results cont.

EfficacyFigure 4. Time to First Report of Pain Relief: Rimegepant Versus All OTCs

• Rimegepant was significantly more effective for time to first report of pain freedom (Figures 5, 6, and 7); significant superiority was maintained through 4 hours postdose

Results

• Of the 2348 randomized subjects in the 2 trials, 2156 were evaluated for efficacy (rimegepant n=1080, placebo n=1076)

• The baseline demographics of the subgroups are shown in Table 1

Subjects

Efficacy• Rimegepant showed significantly better efficacy than AAC, ibuprofen, and all OTC NSAIDs in terms of

time to first report of pain relief (Figures 2, 3, and 4) • Statistically significant superiority was maintained through 4 hours postdose

Figure 2. Time to First Report of Pain Relief: Rimegepant Versus AAC

Figure 3. Time to First Report of Pain Relief: Rimegepant Versus Ibuprofen

Rimegepant 75 mgN=1080n (%)

AACN=78n (%)

IbuprofenN=91n (%)

All OTCN=241n (%)

Age, years 40.5 (12.1) 40.3 (11.4) 41.3 (11.8) 41.4 (12.0)Sex, n (%)

Female 943 (87.3) 66 (84.6) 83 (91.2) 213 (88.4)Male 137 (12.7) 12 (15.4) 8 (8.8) 28 (11.6)

BMI, kg/m2 30.6 (7.8) 31.1 (9.5) 28.9 (7.5) 29.7 (8.5)AAC, acetaminophen/aspirin/caffeine; OTC, over-the-counter; BMI, body mass index

Table 1. Demographics of the Subgroups at Baseline

Figure 5. Time to First Report of Pain Freedom: Rimegepant Versus AAC

Figure 6. Time to First Report of Pain Freedom: Rimegepant Versus Ibuprofen

Log-rank P=.0067

Log-rank P=.0223

Log-rank P=.0037

Log-rank P=.0013

Log-rank P=.0002

Log-rank P<.0001

• Subjects used an eDiary to record data from predose through 48 hours postdose• Rescue medication was allowed after 2 hours postdose

• A limitation of this analysis is that rimegepant was taken ≥2 hours earlier in the migraine attack than the NSAID rescue medications

Limitation

Rimegepant 75 mg Is More Effective Than Nonsteroidal Anti-Inflammatory Drugs for the Acute Treatment of Migraine: Post Hoc Analysis of Data From 2 Phase 3 TrialsAndrew Blumenfeld, MD1; Dawn C. Buse, PhD2; Ira Turner, MD3; David A. Stock, PhD4; Beth Morris, BS4; Vladimir Coric, MD4; Robert Croop, MD4

1 Headache Center of Southern California, Carlsbad, CA; 2 Albert Einstein College of Medicine, Bronx, NY; 3 Island Neurological Associates, Plainview, NY; 4 Biohaven Pharmaceuticals, Inc., New Haven, CT

Poster No. IHC-PO-367

References: 1. Lipton RB et al. Headache. 2018;58:1336–37 (Poster #PS123LB); 2. Lipton RB et al. N Engl J Med. 2019;381:142-49; 3. Croop R et al. Lancet. 2019. doi: 10.1016/S0140-6736(19)31606-X. Disclosures This study was sponsored by Biohaven Pharmaceuticals. AB, DB, and IT have received honoraria and research support from Biohaven Pharmaceuticals. DAS, BAM, VC, and RC are employed by and own stock/stock options in Biohaven Pharmaceuticals. 19th International Headache Congress | September 5-8, 2019 | Dublin, Ireland

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Rimegepant is an investigational new drug, not approved or authorized for marketingin the U.S. or any country for any indication or treatment of any disease or condition.This material is being made available through Biohaven’s Medical Affairs Department.