Rimegepant 75 mg Demonstrates Safety and Tolerability Similar to Placebo With No Effects of Age, Sex, or Race in 3 Phase 3 TrialsJack Schim, MD1; Susan Hutchinson, MD2; Richard B. Lipton, MD3; Elyse G. Stock, MD4; Alexandra Thiry, PhD4; Charles M. Conway, PhD4; Christopher M. Jensen, PharmD4; Beth Morris, BA4; Vladimir Coric, MD4; Robert Croop, MD4

1 Headache Center of Southern California, Carlsbad, CA; 2 Orange County Migraine & Headache Center, Irvine, CA, USA; 3 Albert Einstein College of Medicine, Bronx, NY, USA; 4 Biohaven Pharmaceuticals, New Haven, CT, USA

Poster No. P7.003

References: 1. Lipton RB et al. Headache. 2018;58:1336–37 (Poster #PS123LB); 2. Lipton RB et al. NEJM. 2019;381:142-49; 3. Croop R et al. Lancet. 2019;394(10200):737-745. Disclosures This study was sponsored by Biohaven Pharmaceuticals. JS, SH, and RBL have received honoraria and research support from Biohaven Pharmaceuticals; RBL is also a stockholder. AT, CMC, CMJ, BM, VC, and RC are employed by and own stock/stock options in Biohaven Pharmaceuticals.

Rimegepant 75 mg

N=1749n (%)

PlaceboN=1758n (%)

Pain relief, 2 h 1013 (57.9) 771 (43.9)Ability to function normally, 2 h 611 (34.9) 419 (23.8)Sustained pain relief, 2–24 h 760 (43.5) 482 (27.4)Rescue medication use within 24 h 319 (18.2) 569 (32.4)Sustained pain relief, 2–48 h 660 (37.8) 422 (24.0)Freedom from photophobia,a 2 h 545 (35.1) 376 (23.9)Sustained pain freedom, 2–24 h 247 (14.1) 120 (6.8)Freedom from phonophobia,b 2 h 454 (39.2) 348 (29.3)Sustained pain freedom, 2–48 h 206 (11.8) 108 (6.2)Freedom from nausea,c 2 h 523 (48.8) 473 (43.5)Pain relapse,d 2–48 h 145 (41.7) 107 (50.0)

MBS, most bothersome symptomaRimegepant (n=1552), placebo (n=1571)bRimegepant (n=1158), placebo (n=1187)cRimegepant (n=1070), placebo (n=1088)dRimegepant (n=351), placebo (n=215)

• In selecting pharmacotherapy for acute treatment of migraine, the sex, age, and race of patients can complicate well known safety and tolerability issues, such as adverse events causing delays or avoidance of treatment and cardiovascular contraindications with triptans

• Rimegepant is an FDA-approved, 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 trials1-3

• Rimegepant orally disintegrating tablet (ODT) demonstrated statistically significant pain relief and return to normal function at 60 minutes sustained through 48 hours postdose

• The objective of this pooled analysis was to evaluate the effects of subject sex, age, and race on the safety and tolerability of rimegepant 75 mg and placebo

Objective

• Three double-blind, randomized, placebo-controlled, multicenter trials of identical design (Figure 1) were conducted utilizing an oral tablet (Study 301, NCT03235479; Study 302, NCT03237845) and an ODT (Study 303, NCT03461757)

Methods

Figure 1. Study Design

• Subjects used an eDiary to record data from predose through 48 hours postdose

• Aged ≥18 years, with ≥1-year history of migraine with or without aura• 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

• Safety assessments: adverse events (AEs), ECGs, vital signs, physical measurements, routine laboratory tests, including liver function tests

• Coprimary efficacy endpoints: pain freedom at 2 hours postdose and freedom from the most bothersome symptom (MBS) at 2 hours postdose

• A range of secondary endpoints were assessed to determine efficacy at timepoints out to 48 hours postdose

Assessments

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

• Subjects were grouped by sex (female, male), age (<40, ≥40, <65, ≥65 years), and race (white, non-white) for analyses of AEs

• Efficacy analyses were performed on the modified intent-to-treat population• Efficacy endpoints were evaluated using Cochran-Mantel Haenszel tests and

stratified by use of preventive medication; noncompleters were classified as failures

Statistical Analysis

Introduction

• Pooled efficacy results were similar to the individual trials and showed that rimegepant was more effective than placebo for the coprimary efficacy endpoints of freedom from pain (20.1% vs 12.2%) and freedom from the MBS (36.4% vs 26.6%) at 2 hours postdose

• As shown in Table 4, the pooled analysis found that a single dose of rimegepant 75 mg was more effective than placebo on multiple secondary efficacy endpoints, including:– Pain relief and ability to function normally– Freedom from migraine associated symptoms– Sustained efficacy endpoints from 2 through 48 hours postdose– Rescue medication use

Table 4. Secondary Endpoints in the Pooled Population

Conclusions• Pooled results from 3 Phase 3 randomized controlled clinical

trials in the acute treatment of migraine demonstrate that the safety and tolerability of rimegepant were similar to placebo

• There were no meaningful differences in safety and tolerability between rimegepant and placebo in the sex, age, and race subgroups

• These results confirm that rimegepant has a favorable benefit/risk profile for the acute treatment of migraine

Results cont.Benefits

Rimegepant 75 mgN=1771n (%)

PlaceboN=1782

n (%)

<40 YEARS N=888 N=896

≥1 AE 98 (11.0) 81 (9.0)

Nausea 16 (1.8) 9 (1.0)

Urinary tract infection 7 (.8) 6 (.7)

Treatment-related SAEs 0 0

≥40 YEARS N=883 N=886

≥1 AE 94 (10.6) 73 (8.2)

Nausea 10 (1.1) 5 (.6)

Urinary tract infection 7 (.8) 0

Treatment-related SAEs 0 0

<65 YEARS N=1735 N=1730

≥1 AE 187 (10.8) 149 (8.6)

Nausea 25 (1.4) 12 (.7)

Urinary tract infection 13 (.7) 6 (.3)

Treatment-related SAEs 0 0

≥65 YEARS N=36 N=52

≥1 AE 5 (13.9) 5 (9.6)

Nausea 1 (2.8) 2 (3.8)

Urinary tract infection 1 (2.8) 0

Treatment-related SAEs 0 0

WHITE N=1322 N=1378

≥1 AE 138 (10.4) 121 (8.8)

Nausea 18 (1.4) 12 (.9)

Urinary tract infection 10 (.8) 4 (.3)

Treatment-related SAEs 0 0

NON-WHITE N=449 N=404

≥1 AE 54 (12.1) 33 (8.2)

Nausea 8 (1.8) 2 (.1)

Urinary tract infection 4 (.9) 2 (.1)

Treatment-related SAEs 0 0

AE, adverse event; SAE, serious adverse event

Results cont.Safety

Table 3. Pooled On-Treatment Adverse Events (by Age and Race)

Rimegepant 75 mgN=1771n (%)

PlaceboN=1782

n (%)

FEMALE N=1529 N=1534

≥1 AE 171 (11.2) 136 (8.9)Nausea 23 (1.5) 11 (.7)Urinary tract infection 14 (.9) 6 (.4)

Treatment-related SAEs 0 0

MALE N=242 N=248

≥1 AE 21 (8.7) 18 (7.3)Nausea 3 (1.2) 3 (1.2)Nasopharyngitis 2 (.8) 0

Treatment-related SAEs 0 0

AE, adverse event; SAE, serious adverse event

Rimegepant 75 mgN=1771n (%)

PlaceboN=1782

n (%)

SEXFemale 1529 (86.3) 1534 (86.1)Male 242 (13.7) 248 (13.9)

AGE, YEARS<40 888 (50.1) 896 (50.3)≥40 883 (49.9) 886 (49.7)<65 1735 (98.0) 1730 (97.1)≥65 36 (2.0) 52 (2.9)

RACEWhite 1322 (74.6) 1378 (77.3)Non-whitea 449 (25.4) 404 (22.7)

aIncludes Black/African-American, Asian, and other

• In total, 3553 subjects were evaluated for safety (rimegepant n=1771, placebo n=1782), and 3507 subjects were evaluated for efficacy (rimegepant n=1749, placebo n=1758)

• The sex, age, and race subgroups were demographically balanced (Table 1)• The most common historical MBS was photophobia (57%) • About 15% of subjects were using preventive treatment

Safety

ResultsSubjects

• A total of 14.2% (252/1771) and 11.7% (209/1782) of subjects in the rimegepant and placebo groups, respectively, experienced at least 1 AE

• The most common AEs were nausea and urinary tract infection (≤1.5%)• No serious treatment-related AEs were reported• Tables 2 and 3 show that sex, age, and race had no effect on safety outcomes

Table 2. Pooled On-Treatment Adverse Events (by Sex)

Table 1. Pooled Population Demographics by Sex, Age, and Race

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