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, MD 1,2,3 ; Vladimir Coric, MD 4 ; Elyse G. Stock, MD 4 ; David Stock, PhD 4 ; Beth A. Morris, BA 4 ; Timothy J. McCormack, BA 4 ; Marianne Frost, MA 4 ; Kimberly Gentile, BS 4 ; Gene M. Dubowchik, PhD 4 ; Charles M. Conway, PhD 4 ; Robert Croop, MD 4 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
15
Embed
Efficacy, Safety, and Tolerability of Rimegepant 75 mg, an ... · –Phase 3 Study 301 is presented as a late-breaking poster (PS123LB) Q & A. Thank You! Title: Rimegepant Study 302
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
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 millionContraindicated
or 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 mgN=537
PlaceboN=535
TotalN=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 (%)
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) 0.0001aSecondary endpoints were tested hierarchically in the order shown at P=0.05bRimegepant n=489, placebo n=477; cRimegepant n=362, placebo n=374; dRimegepant n=355, placebo n=336; eRimegepant n=105, placebo n=64fExploratory 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
0
20
40
60
80
100
2 hr 3 hr 4 hr 6 hr 8 hr
% o
f Pat
ient
s Pai
n Fr
ee
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.
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
AEs related to treatment 10 (1.8) 3 (.6)Serious AEs 1 (0.2)b 2 (0.4)AEs leading to discontinuation 0 0
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 0 0
Serum AST or ALT > 5x ULN 0 0
Bilirubin elevations > 2x ULN 0 0
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)