Presented at the 60th Annual Scientific Meeting of the American Headache Society, 30 June 2018, San Francisco, CA (Poster #PS123LB)

Efficacy, Safety, and Tolerability of Rimegepant 75 mg, an Oral CGRP Receptor Antagonist, for the Acute Treatment of Migraine: Results from a Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial, Study 301Richard B. Lipton, MD1,2,3; Charles M. Conway, PhD4; Elyse G. Stock, MD4; David Stock, PhD4; Beth A. Morris, BA4; Timothy J. McCormack, BA4; Marianne Frost, MA4; Kimberly Gentile, BS4; Gene M. Dubowchik, PhD4; Vladimir Coric, MD4; Robert Croop, MD4

1 Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA; 2 Montefiore Medical Center, Bronx, NY, USA; 3 Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA; 4 Biohaven Pharmaceuticals, New Haven, CT, USA

• Several small molecule calcitonin gene-related peptide (CGRP)receptor antagonists — also known as “gepants” — havedemonstrated efficacy in the acute treatment of migraine1-5

• Currently available acute treatments for migraine may be ineffective,intolerable, or contraindicated in many patients

• A prior double-blind, randomized, placebo-controlled, dose-ranging,Phase 2b study in 799 adults with migraine found that rimegepant75 mg was significantly superior to placebo for freedom from pain,nausea, photophobia, and phonophobia at 2, 24, and 48 hourspostdose (P≤.05)4

INTRODUCTION

• Significant and durable clinical effects were seen with a singledose of rimegepant across multiple outcome measures,including pain freedom, freedom from MBS, pain relief,and recovery of normal function

• Rimegepant 75 mg oral tablet demonstrated favorabletolerability and safety, and it was comparable to placebo ontests of liver function

• These clinically meaningful findings complement the positiveresults seen in an identical Phase 3 study (BHV3000-302,NCT03237845) and a previous Phase 2b study

• Rimegepant may ultimately offer patients a novel approachfor the acute treatment of migraine

CONCLUSIONS

1. Ho TW et al. Lancet. 2008;372(9656):2115-2123.; 2. Diener HC et al.Cephalalgia. 2011;31(5):573-584.; 3. Hewitt DJ et al. Cephalalgia.2011;31(6):712-722.; 4. Marcus R et al. Cephalalgia. 2014;34(2):114-125.;5. Voss T et al. Cephalalgia. 2016;36(9):887-898.; 6. ICHD-3 beta. Cephalalgia.2013;33(9):629-808.

REFERENCES

• This was a double-blind, randomized, placebo-controlled, multicenterstudy (Study BHV3000-301, NCT03235479)

METHODS

The objective of this Phase 3 study was to compare the efficacy, safety, and tolerability of rimegepant 75 mg oral tablet with placebo in the acute treatment of migraine in adults

OBJECTIVES

• RBL has received honoraria and research support from BiohavenPharmaceuticals; he is also a stockholder

• CMC, EGS, DS, BAM, TJM, MF, KG, GMD, VC, and RC are employeesand stockholders in Biohaven Pharmaceuticals

DISCLOSURES

Table 2. Efficacy of Rimegepant Versus Placebo

• As shown in Table 3, the safety and tolerability of rimegepant weresimilar to placebo

Safety

Efficacy• At 2 hours postdose, relative to placebo-treated subjects, rimegepant-

treated subjects had:– Significantly higher pain-free rates (19.2% vs 14.2%, P=0.0298)– A significantly greater likelihood of being free from the MBS

(36.6% vs 27.7%, P=0.0016)

AE, adverse eventaBoth subjects with SAEs in the rimegepant group had not been dosed before onset of the SAEs

• The coprimary efficacy endpoints were:– Pain freedom at 2 hours postdose– Freedom from the most bothersome symptom (MBS) at 2 hours

postdose• Safety assessments included adverse events (AEs),

electrocardiograms, vital signs, physical measurements, and routinelaboratory tests, including assessment of liver function

Assessments

• Efficacy analyses were performed on the modified intent-to-treat(mITT) population: subjects who had a qualifying migraine attack,took study medication, and provided at least 1 evaluable postbaselineefficacy data point

• Safety analyses were conducted on enrolled subjects who took anydose of study medication (rimegepant or placebo)

Statistical Analyses

• Subjects were provided with an electronic diary, instructed on itsproper use, and asked to provide information about the treated attackfrom immediately predose to 48 hours after taking study medication

Figure 1. Study Schema

Endpoints Rimegepant N=543, n (%)

PlaceboN=541, n (%) P-valuea

COPRIMARY

Pain-free at 2 hours 104 (19.2) 77 (14.2) 0.0298Free of MBS at 2 hours 199 (36.6) 150 (27.7) 0.0016

SECONDARY

Photophobia-free at 2 hoursb 164 (34.9) 120 (24.8) 0.0005Phonophobia-free at 2 hoursc 133 (38.6) 113 (30.9) 0.0299Pain relief at 2 hours 304 (56.0) 247 (45.7) 0.0006Nausea-free at 2 hoursd 149 (46.9) 134 (41.6) 0.1815

Rescue medication within 24 hours 111 (20.4) 172 (31.8) <0.0001

Sustained pain-free, 2-24 hours 76 (14.0) 44 (8.1) 0.0020

Sustained pain relief, 2-24 hours 211 (38.9) 151 (27.9) 0.0001Sustained pain-free, 2-48 hours 63 (11.6) 39 (7.2) 0.0130Sustained pain relief, 2-48 hours 183 (33.7) 129 (23.9) 0.0003

Pain relapse from 2-48 hourse 41 (40.1) 38 (50.0) 0.1798Ability to function normally at 2 hours 181 (33.3) 118 (21.8) <0.0001

SELECTED EXPLORATORY

Nausea-free at 3 hoursd 171 (53.8) 139 (43.2) 0.0069Sustained pain freedom, 3-48 hours 110 (20.3) 58 (10.7) <0.0001Sustained pain relief, 3-48 hours 220 (40.5) 146 (27.0) <0.0001Sustained ability to function normally, 2-48 hours 110 (20.3) 69 (12.8) 0.0008

Sustained freedom from the MBS, 2-48 hours 117 (21.6) 71 (13.1) 0.0002

MBS, most bothersome symptomaSecondary endpoints were tested hierarchically in the order shown at P=0.05 bRimegepant (n=470) and placebo (n=483)cRimegepant (n=345) and placebo (n=366)dRimegepant (n=318) and placebo (n=322)eRimegepant (n=104) and placebo (n=77)

RESULTSSubjects• In total, 1162 subjects were randomized to receive rimegepant (n=582)

or placebo (n=580), 1084 were evaluated for efficacy (rimegepantn=543, placebo n=541); and 1095 were evaluated for safety(rimegepant n=546, placebo n=549)

• As shown in Table 1, most subjects (85.5%) were female, with a meanage of 41.6 (12.2) years and a history of 4.7 (1.8) attacks per month

Characteristic RimegepantN=543

PlaceboN=541

TotalN=1084

Age,a years (SD) 41.9 (12.3) 41.3 (12.1) 41.6 (12.2)Female, n (%) 464 (85.5) 463 (85.6) 927 (85.5)Weight, kg (SD) 83.3 (22.2) 82.7 (22.5) 83.0 (22.3)Height, cm (SD) 166.1 (8.5) 166.6 (9.0) 166.4 (8.7)Body-mass index, kg/m2 (SD) 30.1 (7.7) 29.8 (7.7) 30.0 (7.7)Attacks per month, n (SD) 4.8 (1.7) 4.7 (1.8) 4.7 (1.8)Duration of untreated attacks, hr (SD) 30.2 (21.7) 29.4 (21.7) 29.8 (21.7)Historical MBS, n (%)

Photophobia 302 (55.6) 302 (55.8) 604 (55.7)Phonophobia 89 (16.4) 101 (18.7) 190 (17.5)Nausea 152 (28.0) 138 (25.5) 290 (26.8)

Subjects• Eligible subjects were at least 18 years of age, with at least a 1-year

history of ICHD-3 beta migraine, with or without aura6

• A history of 2 to 8 migraine attacks of moderate or severe intensityper month and fewer than 15 monthly headache days (migraine ornonmigraine) over the last 3 months

• Subjects on preventive migraine medication had to be on a stabledose for at least 3 months

Table 1. Demographics and Baseline Characteristics

• From 2 through 8 hours postdose, a single dose of rimegepant,without the use of rescue medications, demonstrated:

– An increasing proportion of pain-free subjects (Figure 2)– A greater proportion of patients achieving normal function (Figure 3)

Table 3. Adverse EventsRimegepantN=546, n (%)

PlaceboN=549, n (%)

Subjects with AEs 69 (12.6) 59 (10.7)Most common AEs with rimegepant

Nausea 5 (0.9) 6 (1.1)Dizziness 4 (0.7) 2 (0.4)

AEs related to treatment 3 (0.5) 1 (0.2)Serious AEsa 2 (0.4) 1 (0.2)AEs leading to discontinuation 0 0

AE, adverse event; AST, aspartate aminotransferase; ALT, alanine transaminase; ULN, upper limit of normal

Table 4. Liver Function Tests

RimegepantN=546, n (%)

PlaceboN=549, n (%)

Liver Function

Serum AST or ALT >ULN 11 (2.0) 20 (3.6)

Serum AST or ALT >3x ULN 1 (0.2) 1 (0.2)

Serum AST or ALT >5x ULN 0 0

Bilirubin elevations >2x ULN 0 0

• Liver function tests showed no signs of hepatotoxicity (Table 4)

Figure 3. Disability Freedom up to 8 Hours Postdose

MBS, most bothersome symptom

Pain freedom represents subjects who report no pain at the timepoint of interest. Percentages represent Non-Completer = Failure (NC=F) estimates of pain freedom and were based on the mITT population.

Data are Kaplan-Meier estimates of the first report of Normal Function. Subjects were censored (not included) at the time they took rescue medication or provided their last data point.

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Figure 2. Pain Freedom from 2 to 8 Hours Postdose

Rimegepant is an investigational new drug, not approved or authorized for marketing in the U.S. or any country for any indication or treatment of any disease or condition. This material is being made available for informational purposes only.