2. Academic Validation
  3. Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial

Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial

  • J Allergy Clin Immunol. 2021 Jul;148(1):164-172.e9. doi: 10.1016/j.jaci.2020.10.015.
Bruce Zuraw 1,  William R Lumry 2,  Douglas T Johnston 3,  Emel Aygören-Pürsün 4,  Aleena Banerji 5,  Jonathan A Bernstein 6,  Sandra C Christiansen 1,  Joshua S Jacobs 7,  Karl V Sitz 8,  Richard G Gower 9,  Remi Gagnon 10,  H James Wedner 11,  Tamar Kinaciyan 12,  Roman Hakl 13,  Jana Hanzlíková 14,  John T Anderson 15,  Donald L McNeil 16,  Stephen B Fritz 17,  William H Yang 18,  Raffi Tachdjian 19,  Paula J Busse 20,  Timothy J Craig 21,  H Henry Li 22,  Henriette Farkas 23,  Jessica M Best 24,  Desiree Clemons 24,  Melanie Cornpropst 24,  Sylvia M Dobo 24,  Heather A Iocca 24,  Deborah Kargl 24,  Eniko Nagy 24,  Sharon C Murray 24,  Phil Collis 24,  William P Sheridan 25,  Marcus Maurer 26,  Marc A Riedl 1
Affiliations

Affiliations

  • 1 University of California San Diego, San Diego, Calif.
  • 2 Allergy & Asthma Specialists of Dallas, Dallas, Tex.
  • 3 Asthma and Allergy Specialists, Charlotte, NC.
  • 4 University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
  • 5 Massachusetts General Hospital, Harvard Medical School, Boston, Mass.
  • 6 University of Cincinnati, Cincinnati, Ohio.
  • 7 Allergy and Asthma Clinical Research, Walnut Creek, Calif.
  • 8 Little Rock Allergy and Asthma Clinical Research Center, Little Rock, Ark.
  • 9 University of Washington School of Medicine, Marycliff Clinical Research, Spokane, Wash.
  • 10 Clinique Spécialisée en Allergie de la Capitale, Québec, Canada.
  • 11 Washington University School of Medicine, St Louis, Mo.
  • 12 Medical University of Vienna, Department of Dermatology, Vienna, Austria.
  • 13 Department of Clinical Immunology and Allergology, St. Anne's University Hospital in Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
  • 14 Faculty Hospital, Department of Allergology and Immunology, Plzen, Czech Republic.
  • 15 Clinical Research Center of Alabama, Birmingham, Ala.
  • 16 Optimed Research Ltd, Columbus, Ohio.
  • 17 Portland Clinical Research, Portland, Ore.
  • 18 Ottawa Allergy Research Corporation, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
  • 19 Department of Pediatrics, University of California, Los Angeles, Calif.
  • 20 Division of Clinical Immunology and Allergy, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
  • 21 Department of Medicine and Pediatrics, Penn State University, Hershey, Pa.
  • 22 Institute for Asthma and Allergy, Chevy Chase, Md.
  • 23 Hungarian Angioedema Reference Center, Third Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
  • 24 BioCryst Pharmaceuticals, Durham, NC.
  • 25 BioCryst Pharmaceuticals, Durham, NC. Electronic address: bsheridan@biocryst.com.
  • 26 Dermatological Allergology, Department of Dermatology and Allergy, Charité Universitätsmedizin Berlin, Berlin, Germany.
PMID: 33098856 DOI: 10.1016/j.jaci.2020.10.015
Abstract

Background: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma Kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks.

Objective: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial).

Methods: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period.

Results: A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P < .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred.

Conclusion: Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day.

Keywords

BCX7353; C1 inhibitor; HAE; berotralstat; efficacy; hereditary angioedema; kallikrein inhibitor; long-term prophylaxis; prophylaxis; safety.

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