Efficacy, Safety, and Tolerability of Rimegepant 75 mg, an Efficacy, - - PowerPoint PPT Presentation

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 302

Richard B. Lipton, MD1,2,3; Vladimir Coric, MD4; 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; Charles M. Conway, PhD4; 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, Inc., New Haven, CT, USA

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 302

Richard B. Lipton, MD1,2,3; Vladimir Coric, MD4; 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; Charles M. Conway, PhD4; 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, Inc., New Haven, CT, USA

2

Disclosures

• Biohaven Pharmaceuticals funded the study, was responsible for study oversight, and performed data

management and analysis

• Richard B. Lipton, MD, serves on the editorial board of Neurology and Cephalalgia and as senior

advisor to Headache but is not paid for his roles on Neurology or Headache. He has received research support from the NIH. He also receives support from the Migraine Research Foundation and the National Headache Foundation. He receives research grants from Allergan, Amgen, Dr. Reddy’s Laboratories, and Novartis. He has reviewed for the NIA and NINDS and serves as consultant, advisory board member, or has received honoraria from Alder, Allergan, Amgen, Autonomic Technologies, Avanir, Boston Scientific, CoLucid, Dr. Reddy’s Laboratories, electroCore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Novartis, Teva, and Vedanta. He receives royalties from Wolff’s Headache (8th Edition, Oxford Press University, 2009) and Informa. He holds stock options in eNeura Therapeutics and Biohaven Pharmaceuticals.

• All other authors are employed by and hold stock/stock options in Biohaven Pharmaceuticals

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.

3

Triptans: Nonresponse, Recurrence, and Serious AEs for Many Patients Serotonin 5-HT1B/1D receptor agonists (triptans) have been the most widely prescribed acute treatment of migraine for decades1

• 1. Loder E. NEJM. 2010;363:63-70.; 2. Lipton RB et al. Headache. 2017;57:1026-40.; 3. Cameron C et al. Headache. 2015;55 Suppl 4:221-35.; 4. Buse DC et al.
• Headache. 2017;57:31-44.; 5. Lipton RB et al. Headache. 2017;57:1507-21.

Do not respond2

34% ~3.5 million

Contraindicated

• r use with caution4,5

30%-40%

Have attack recurrence3

4

Study Design

• Double-blind, randomized, placebo-controlled, multicenter Phase 3 study
• Eligible subjects:

–At least 18 years of age –At least a 1-year history of migraine (ICHD-3 beta1) –2-8 migraine attacks of moderate or severe intensity per month –Fewer than 15 days with headache per month (migraine or non-migraine) over the last 3 months –Any preventive migraine medication had to be stable for at least 3 months

• Randomized to receive rimegepant 75 mg or placebo
• Instructed to treat a single migraine attack

ICHD-3 beta. Cephalalgia. 2013;33(9):629-808.

5

Subject Demographics

Characteristic Rimegepant 75 mg N=537 Placebo N=535 Total N=1072 Age, years (SD) 40.2 (11.9) 40.9 (12.1) 40.6 (12.0) Female, n (%) 479 (89.2) 472 (88.2) 951 (88.7) Body mass index, kg/m2 (SD) 30.1 (7.9) 31.8 (8.5) 31.4 (8.2) Attacks per month, n (SD) 4.5 (1.9) 4.6 (1.8) 4.6 (1.8) Duration of untreated attacks, hr (SD) 32.0 (22.5) 32.9 (21.7) 32.5 (22.1) Historical MBS, n (%) Photophobia 316 (58.8) 303 (56.6) 619 (57.7) Phonophobia 79 (14.7) 90 (16.8) 169 (15.8) Nausea 142 (26.4) 142 (26.5) 284 (26.5)

SD, Standard Deviation MBS, most bothersome symptom

6

Subject Disposition

Rimegepant 75 mg Placebo

Randomized 594 592 Received study treatment 543 543 Did not receive study treatmenta 51 49 Completed acute phase 538 542 Discontinueda 5 1 Analyzed Safety 543 543 Modified intent-to-treat 537 535

aMost common reasons were lost to follow-up and no qualifying migraine attack

7

Superior to Placebo on Both Coprimary Efficacy Endpoints

19.6 37.6 12.0 25.2

10 20 30 40 50 60 70

Pain Freedom at 2 hours postdose Freedom from the MBS at 2 hours postdose

Rimegepant Placebo N=537 N=535

Proportion of Subjects

P=0.0006 P<0.0001

MBS, most bothersome symptom

8

Significant Superiority on Key Secondary Endpoints Durability Evident from 2 through 48 Hours

Endpoints Rimegepant 75 mg N=537, n (%) Placebo N=535, n (%) P-valuea

Photophobia-free at 2 hoursb 183 (37.4) 106 (22.3) <0.0001 Phonophobia-free at 2 hoursc 133 (36.7) 100 (26.8) 0.0039 Pain relief at 2 hours 312 (58.1) 229 (42.8) <0.0001 Nausea-free at 2 hoursd 171 (48.1) 145 (43.3) 0.2084 Rescue medication within 24 hours 113 (21.0) 198 (37.0) <0.0001 Sustained pain-free, 2-24 hours 66 (12.3) 38 (7.1) 0.0040 Sustained pain relief, 2-24 hours 229 (42.6) 142 (26.5) <0.0001 Sustained pain-free, 2-48 hours 53 (9.9) 32 (6.0) 0.0181 Sustained pain relief, 2-48 hours 195 (36.3) 121 (22.6) <0.0001 Pain relapse from 2 to 48 hourse 52 (49.6) 32 (50.0) 0.9648 Ability to function normally at 2 hours 175 (32.6) 125 (23.4) 0.0007 Nausea-free at 3 hoursd,f 209 (58.8) 167 (49.7) 0.0156 Sustained ability to function normally, 2-48 hoursf 105 (19.6) 67 (12.5) 0.0016 Sustained freedom from the MBS, 2-48 hoursf 112 (20.9) 65 (12.2) 0.0001

aSecondary endpoints were tested hierarchically in the order shown at P=0.05 bRimegepant n=489, placebo n=477; cRimegepant n=362, placebo n=374; dRimegepant n=355, placebo n=336; eRimegepant n=105, placebo n=64 fExploratory endpoint

9

Pain Freedom with Single Dose: Increasing Benefit Over Time

Pain Freedom represents subjects that 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. Single Dose of Rimegepant, No Rescue Meds

20 40 60 80 100 2 hr 3 hr 4 hr 6 hr 8 hr

% of Patients Pain Free

Pain Freedom 2-8 Hours Post-Single Dosing with Rimegepant 75 mg

Time

Rimegepant 75 mg (n=537) Placebo (n=535) Percent (%) difference versus placebo at each time point

20% 48% 30% 37% 43%

10

Greater Proportion of Subjects Achieving Pain Relief and Normal Function Without Additional Dosing or Rescue Medications

Pain Relief up to 8 Hours Postdose

Pain Relief represents the first report of either mild pain or no pain. Probabilities are Kaplan-Meier estimates; subjects were censored (not included) at the time they took rescue medication or provided their last data point.

Disability Freedom up to 8 Hours Postdose

Four-point scale: 0=normal function, 1=mild impairment, 2=severe impairment, 3=required bedrest 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.

11

Safety Profile Similar to Placebo

Adverse Event Rimegepant 75 mg N = 543, n (%) Placebo N = 543, n (%)

Subjects with AE 93 (17.1) 77 (14.2) AEs reported by ≥ 1% of subjectsa Nausea 10 (1.8) 6 (1.1) Urinary tract infection 8 (1.5) 6 (1.1) AEs related to treatment 10 (1.8) 3 (.6) Serious AEs 1 (0.2)b 2 (0.4) AEs leading to discontinuation

AE, adverse event; aIn either treatment group; bBack pain; unrelated to treatment

12

Liver Safety

Liver Function Tests Rimegepant 75 mg N = 543, n (%) Placebo N = 543, n (%)

Serum AST or ALT > ULN 13 (2.4) 12 (2.2) Serum AST or ALT > 3x ULN Serum AST or ALT > 5x ULN Bilirubin elevations > 2x ULN

AST, aspartate transaminase; ALT, alanine transaminase; ULN, upper limit of normal

13

Conclusions

• Coprimary endpoints met

– Pain Freedom at 2 hours postdose – Freedom From the Most Bothersome Symptom at 2 hours postdose

• Broad and clinically important drug benefit with single dose of rimegepant

– Majority of patients achieve Pain Relief – Durability of benefit (24 and 48 hours) – Lower use of rescue meds – Greater proportion of patients achieving normal function

• Excellent safety profile similar to placebo including liver function tests
• Tolerability profile similar to placebo and favorable compared to historical

triptan experience

• Consistent results across endpoints and all efficacy trials

– Phase 3 Study 301 is presented as a late-breaking poster (PS123LB)

Q & A

Thank You!