Rimegepant 75 mg, an Oral Calcitonin Gene-Related Peptide Antagonist, - - PowerPoint PPT Presentation

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Richard B. Lipton, MD1; Vladimir Coric, MD2; Elyse G. Stock, MD2; David A. Stock, PhD2; Beth A. Morris, BA2; Timothy J. McCormack, BA2; Marianne Frost, MA2; Kimberly Gentile, BS2; Christopher M. Jensen, PharmD2; Gene M. Dubowchik, PhD2; Charles M. Conway, PhD2; Robert Croop, MD2; Peter J. Goadsby, MD, PhD3

1 Albert Einstein College of Medicine, Bronx, NY, USA; 2 Biohaven Pharmaceuticals, Inc., New Haven, CT, USA; 3 NIHR-Wellcome Trust King’s Clinical Research Facility, King’s College London, UK

Rimegepant 75 mg, an Oral Calcitonin Gene-Related Peptide Antagonist, for the Acute Treatment of Migraine: Two Phase 3, Double-Blind, Randomized, Placebo-Controlled Trials

Objective

• Compare the efficacy, safety, and tolerability of

rimegepant 75 mg oral tablet with placebo in the acute treatment of migraine in adults

Randomization and Treatment

• Randomized 1:1 to rimegepant 75 mg or placebo
• Instructed to treat a single migraine attack of

moderate to severe intensity

• Groups were balanced in terms of demographics

Coprimary Endpoints (at 2 hours postdose)

• Pain freedom
• Freedom from the most bothersome symptom (MBS)

Disposition 301 302

Randomized 1162 1186 Rimegepant 582 594 Placebo 580 592 Evaluated for Efficacy 1084 1072 Rimegepant 543 537 Placebo 541 535 Evaluated for Safety 1095 1086 Rimegepant 546 543 Placebo 549 543

Demographics 301 302

Female, % 85.5 88.7 Agea, years 41.6 (12.2) 40.6 (12.0) Hx of Attacks/Montha, n 4.7 (1.8) 4.6 (1.8)

aMean (SD)

Disposition 301

Randomized 1162 Rimegepant 582 Placebo 580 Evaluated for Efficacy 1084 Rimegepant 543 Placebo 541 Evaluated for Safety 1095 Rimegepant 546 Placebo 549

Demographics 301

Female, % 85.5 Agea, years 41.6 (12.2) Hx of Attacks/Montha, n 4.7 (1.8)

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.

aEndpoints were tested hierarchically in the order shown at P=0.05; b-iThe following numbers indicate the number of subjects in the denominator for each percentage: bRimegepant n=470, Placebo n=483; cRimegepant n=345, Placebo n=366; dRimegepant n=318, Placebo n=322; eRimegepant n=104, Placebo n=77; fRimegepant n=489,

Placebo n=477; gRimegepant n=362, Placebo n=374; hRimegepant n=355, Placebo n=336; iRimegepant n=105, Placebo n=64

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Met Coprimary and Key Secondary Endpoints in Both Studies

Sustained Efficacy through 48 Hours on Multiple Measures After a Single Dose of Rimegepant Study 301 302

Endpoints Rimegepant

N=543, n (%)

Placebo

N=541, n (%)

P-value Rimegepant

N=537, n (%)

Placebo

N=535, n (%)

P-value COPRIMARY (AT 2 HOURS POSTDOSE) Pain freedom 104 (19.2) 77 (14.2) 0.0298 105 (19.6) 64 (12.0) 0.0006 Freedom from the MBS 199 (36.6) 150 (27.7) 0.0016 202 (37.6) 135 (25.2) <0.0001 SECONDARYa Photophobia-free at 2 hours 164 (34.9) 120 (24.8) 0.0005b 183 (37.4) 106 (22.3) <0.0001f Phonophobia-free at 2 hours 133 (38.6) 113 (30.9) 0.0299c 133 (36.7) 100 (26.8) 0.0039g Pain relief at 2 hours 304 (56.0) 247 (45.7) 0.0006 312 (58.1) 229 (42.8) <0.0001 Nausea-free at 2 hours 149 (46.9) 134 (41.6) 0.1815d 171 (48.1) 145 (43.3) 0.2084h Rescue medication within 24 hours 111 (20.4) 172 (31.8) <0.0001 113 (21.0) 198 (37.0) <0.0001 Sustained pain-free, 2-24 hours 76 (14.0) 44 (8.1) 0.0020 66 (12.3) 38 (7.1) 0.0040 Sustained pain relief, 2-24 hours 211 (38.9) 151 (27.9) 0.0001 229 (42.6) 142 (26.5) <0.0001 Sustained pain-free, 2-48 hours 63 (11.6) 39 (7.2) 0.0130 53 (9.9) 32 (6.0) 0.0181 Sustained pain relief, 2-48 hours 183 (33.7) 129 (23.9) 0.0003 195 (36.3) 121 (22.6) <0.0001 Pain relapse from 2 to 48 hours 41 (40.1) 38 (50.0) 0.1798e 52 (49.6) 32 (50.0) 0.9648i Ability to function normally at 2 hours 181 (33.3) 118 (21.8) <0.0001 175 (32.6) 125 (23.4) 0.0007 SELECTED EXPLORATORY Nausea-free at 3 hours 171 (53.8) 139 (43.2) 0.0069d 209 (58.9) 167 (49.7) 0.0156h Sustained ability to function normally, 2-48 hours 110 (20.3) 69 (12.8) 0.0008 105 (19.6) 67 (12.5) 0.0016 Sustained freedom from the MBS, 2-48 hours 117 (21.6) 71 (13.1) 0.0002 112 (20.9) 65 (12.2) 0.0001

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Rimegepant Safety and Tolerability Profile Similar to Placebo

Rimegepant Similar to Placebo on Liver Function Tests (Studies 301 and 302 – Combined) Study 301 302

ADVERSE EVENTS Rimegepant

N=546, n (%)

Placebo

N=549, n (%)

Rimegepant

N= 543, n (%)

Placebo

N=543, n (%)

Subjects with AEs 69 (12.6) 59 (10.7) 93 (17.1) 77 (14.2) Most common AEs with rimegepant Nausea 5 (0.9) 6 (1.1) 10 (1.8)b 6 (1.1) Dizziness (301) / Urinary tract infection (302) 4 (0.7) 2 (0.4) 8 (1.5)b 6 (1.1) AEs related to treatment 3 (0.5) 1 (0.2) 10 (1.8)b 3 (0.6) Serious AEs 2 (0.4)a 1 (0.2) 1 (0.2)b 2 (0.4) AEs leading to discontinuation 0 0

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

aNeither subject had been dosed before the onset of the SAEs; bBack pain, unrelated to treatment

Study 301

ADVERSE EVENTS Rimegepant

N=546, n (%)

Placebo

N=549, n (%)

Subjects with AEs 69 (12.6) 59 (10.7) Most common AEs with rimegepant Nausea 5 (0.9)a 6 (1.1) Dizziness (301) / Urinary tract infection (302) 4 (0.7)a 2 (0.4) AEs related to treatment 3 (0.5)a 1 (0.2) Serious AEs 2 (0.4)a 1 (0.2) AEs leading to discontinuation 0 0 0 0

Conclusions

• Two identical RCTs show that in comparison with placebo, rimegepant delivers significant benefits on the coprimary

endpoints — 2-hour pain freedom and freedom from the MBS

• Safety and tolerability profiles were comparable to placebo

Rimegepant n=1089, n (%) Placebo n=1092, n (%) Serum AST or ALT > ULN 24 (2.2) 32 (2.9) Serum AST or ALT > 3x ULN 1 (0.1) 1 (0.1) Serum AST or ALT > 5x ULN Bilirubin > 2x ULN