Rimegepant 75 Mg Provides Early And Sustained Relief Of Migraine With A Single Oral Dose: Results From 3 Phase 3 Clinical Trials

Authors: Jelena M. Pavlovic, MD, PhD,1 David W. Dodick, MD,2 Deborah Friedman, MD, MPH,3 Stewart Tepper, MD,4 Lawrence C. Newman, MD,5 Richard B. Lipton, MD,1 Elyse G. Stock, MD,6 Alexandra Thiry, PhD,6 Charles M. Conway, PhD,6 Christopher M. Jensen, PharmD,6 Beth Morris, BA,6 Vladimir Coric, MD,6 Robert Croop, MD6

Affiliations: 1. Albert Einstein College of Medicine, Bronx, NY USA; 2. Mayo Clinic Arizona, Scottsdale, AZ, USA; 3. University of Texas Southwestern Medical Center, Dallas, TX, USA; 4. Geisel School of Medicine at Dartmouth, Hanover, NH, USA; 5. NYU Langone Health, New York, NY, USA; 6. Biohaven Pharmaceuticals, New Haven, CT, USA

Objective:
To compare rimegepant with placebo in the acute treatment of migraine for pain relief and ability to function normally at early (≤2 hours) and sustained (up to 48 hours) endpoints in pooled data from 3 randomized clinical trials.

Design and setting:
Three double-blind, randomized, placebo-controlled, multicenter trials of identical design were conducted in adults with migraine. Subjects were randomized to rimegepant 75 mg tablet (Studies 301 and 302), 75 mg ODT (Study 303), or placebo and instructed to treat 1 migraine attack of moderate to severe pain intensity with a single dose of study medication.

Patients:
Adults 318 years of age with 31-year history of migraine.

Main outcome measures:
The coprimary endpoints were pain freedom and MBS freedom at 2 hours postdose. Pain relief and ability to function normally were evaluated as secondary endpoints.

Results:
Among 3507 subjects evaluated for efficacy (rimegepant n=1749, placebo n=1758), pooled 2-hour pain relief rates (95% CIs) were 57.9% (55.6, 60.2) for rimegepant and 43.9% (41.6, 46.2) for placebo. A single dose of rimegepant without rescue medication was more effective than placebo for sustained pain relief from 2 to 48 hours postdose (37.8% [95% CI 35.5, 40.0] vs 24.0% [95% CI 22.0, 26.0]) and sustained normal function from 2 to 48 hours postdose (22.3% [95% CI 20.3, 24.2] vs 13.7% [95% CI 12.1, 15.3]). Additionally, rimegepant 75 mg ODT numerically separated from placebo on pain relief beginning at 15 minutes postdose and was significantly superior to placebo at 60 minutes for pain relief (36.8% vs 31.2%, P=.0314) and return to normal function (22.3% vs 15.8%, P=.0025).

Conclusions:
A single dose of rimegepant 75 mg was more effective than placebo on efficacy endpoints measured from 2 through 48 hours postdose. Furthermore, rimegepant ODT had early onset of action, demonstrating superiority over placebo on pain relief and return to normal function at 60 minutes postdose.

Disclosures:

Jelena M. Pavlovic, MD, PhD is a consultant for Allergan and serves on the advisory board for Biohaven.

David W. Dodick reports the following conflicts: Consulting: Amgen, University Health Network, Daniel Edelman Inc., Autonomic technologies, Axsome, Allergan, Alder, Biohaven, Charleston Laboratories, Promius, Eli Lilly, eNeura, Neurolief, Novartis, Ipsen, Impel, Satsuma, Supernus, Theranica, Teva, WL Gore, Nocira, XoC, Zosano, Upjohn (Division of Pfizer), Pieris, Revance, Equinox, Salvia, Amzak Health. Honoraria: Foresite Capital, ZP Opco, Oppenheimer, Association of Translational Medicine, Healthlogix, Medicom Worldwide, Medlogix Communications, Mednet, Electrocore, Miller Medical, PeerView, WebMD Health/Medscape, Chameleon, Academy for Continued Healthcare Learning, Sun Pharma (India), Universal meeting management, Haymarket , Global Scientific Communications, Global Life Sciences, Global Access Meetings, UpToDate (Elsevier), Oxford University Press, Cambridge University Press, Wolters Kluwer Health. Research Support: Department of Defense, National Institutes of Health, Henry Jackson Foundation, Sperling Foundation, American Migraine Foundation, Patient Centered Outcomes Research Institute (PCORI). Stock Options/Shareholder/Patents/Board of Directors: Aural analytics, Healint, Theranica, Second Opinion/Mobile Health, Epien (Options/Board), Nocira, Matterhorn/Ontologics (Options/Board), King-Devick Technologies (Options/Board), Precon Health (Options/Board). Patent 17189376.1-1466:vTitle: Botulinum Toxin Dosage Regimen for Chronic Migraine Prophylaxis.

Deborah I. Friedman, MD, is an associate editor of Headache and is on the editorial board of Neurology Reviews and MedScape Migraine Center of Excellence. She has served on advisory boards for member, and received grant support for Alder, Allergan, Amgen, Biohaven, electroCore, Eli Lilly, Impel, Promius, Revance, Supernus, Teva and Zosano. She received grant support from Allergan, Autonomic Technologies, electroCore, Eli Lilly, Merck, and Zosano. She was on the speakers bureau for Allergan, Amgen, electroCore, Supernus and Teva. She received honoraria for content development of CME programs from Miller Communications, PrimeMD and Forefront.

Stewart Tepper, MD, reports the following disclosures: Grants for research (no personal compensation): Alder, Allergan, Amgen, Dr. Reddy’s, ElectroCore, Eli Lilly, eNeura, Neurolief, Novartis, Scion Neurostim, Teva, Zosano. Consultant and/or Advisory Boards: Acorda, Alder, Alexsa, Align Strategies, Allergan, Alphasights, Amgen, Aperture Venture Partners, Aralez Pharmaceuticals Canada, Axsome Therapeutics, BioDelivery Sciences International, Biohaven, Charleston Labs, Decision Resources, DeepBench, Dr. Reddy’s, ElectroCore, Eli Lilly, eNeura, Equinox, ExpertConnect, GLG, GSK, Guidepoint Global, Impel, M3 Global Research, Magellan Rx Management, Marcia Berenson Connected Research and Consulting, Medicxi, Navigant Consulting, Neurolief, Nordic BioTech, Novartis, Pfizer, Reckner Healthcare, Relevale, Satsuma, Scion Neurostim, Slingshot Insights, Sorrento, Spherix Global Insights, Sudler and Hennessey, Teva, Theranica, Thought Leader Select, Trinity Partners, XOC, Zosano. Royalties: Springer. Salary: Dartmouth-Hitchcock Medical Center, American Headache Society. CME honoraria: American Academy of Neurology, Cleveland Clinic Foundation, Diamond Headache Clinic, Elsevier, Forefront Collaborative, Hamilton General Hospital, Ontario, Canada, Henry Ford Hospital, Detroit, Inova, Headache Cooperative of New England, Medical Learning Institute Peerview, Miller Medical Communications, Physicians’ Education Resource, Rockpointe, WebMD/Medscape

Lawrence C. Newman serves as a consultant for Amgen, Alder, Biohaven, Lilly, Teva. He receives royalties from Oxford Univ Press.

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, Biohaven, 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.

Elyse G. Stock, MD, is employed by and holds stock/stock options in Biohaven Pharmaceuticals.

Alexandra Thiry, PhD, is employed by and holds stock/stock options in Biohaven Pharmaceuticals.

Charles M. Conway, PhD, is employed by and holds stock/stock options in Biohaven Pharmaceuticals.

Christopher M. Jensen, PharmD, is employed by and holds stock/stock options in Biohaven Pharmaceuticals.

Beth Morris, BA, is employed by and holds stock/stock options in Biohaven Pharmaceuticals.

Vladimir Coric, MD, is employed by and holds stock/stock options in Biohaven Pharmaceuticals.

Robert Croop, MD, is employed by and holds stock/stock options in Biohaven Pharmaceuticals.

Jelena M. Pavlovic, MD, PhD
Albert Einstein College of Medicine
1225 Morris Park Avenue
Van Etten, Room 3C9B
Bronx, NY 10461
Tel: 718.430.8363
Email: jpavlovi@montefiore.org

David W. Dodick, MD
Mayo Clinic Arizona
13400 East Shea Boulevard
Scottsdale, AZ 85259, USA
Phone: 480-515-6296
Email: Dodick.David@mayo.edu

Deborah I. Friedman, MD, MPH
UT Southwestern Medical Center
5303 Harry Hines Blvd.
Dallas, TX 75390
Phone: 214-645-8300
Email: Deborah.Friedman@UTSouthwestern.edu

Stewart Tepper, MD
Geisel School of Medicine at Dartmouth
1 Rope Ferry Road
Hanover, NH 03755
Phone: 603-650-5104
Email: sjtepper@gmail.com

Lawrence C. Newman, MD
NYU Langone Health
555 Madison Avenue, 3rd Floor
New York, NY 10022
Phone: 646-754-2000
Email: Lawrence.Newman@nyulangone.org

Richard B. Lipton, MD
Montefiore Medical Center
The Saul R. Korey Department of Neurology
Albert Einstein College of Medicine
1165 Morris Park Avenue, Rousso Building, Room 332
Bronx, NY 10461
Phone: 718-430-3886
E-mail: Richard.Lipton@einstein.yu.edu

Elyse G. Stock, MD
Biohaven Pharmaceuticals, Inc.
215 Church Street
New Haven, CT 06510
Phone: 203-404-0410
Email: elyse.stock@biohavenpharma.com

Alexandra C. Thiry, PhD
Biohaven Pharmaceuticals, Inc.
215 Church Street
New Haven, CT 06510
Phone: 203-404-0410
Email: alexandra.thiry@biohavenpharma.com

Charles M. Conway, PhD
Biohaven Pharmaceuticals, Inc.
215 Church Street
New Haven, CT 06510
Phone: 203-404-0410
Email: charlie.conway@biohavenpharma.com

Corresponding author:

Christopher M.
Jensen, PharmD
Biohaven Pharmaceuticals, Inc.
215 Church Street
New Haven, CT 06510
Phone: 203-404-0410
Email: christopher.jensen@biohavenpharma.com

Beth Morris, BA
Biohaven Pharmaceuticals, Inc.
215 Church Street
New Haven, CT 06510
Phone: 203-404-0410
Email: beth.morris@biohavenpharma.com

Vladimir Coric, MD
Biohaven Pharmaceuticals, Inc.
215 Church Street
New Haven, CT 06510
Phone: 203-404-0410
Email: vlad.coric@biohavenpharma.com

Robert Croop, MD
Biohaven Pharmaceuticals, Inc.
215 Church Street
New Haven, CT 06510
Tel: 203-404-0410
Email: robert.croop@biohavenpharma.com

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