Long-term safety and efficacy of once-daily berotralstat in patients with hereditary angioedema: APeX-S final results
- PMID: 40490218
- DOI: 10.1016/j.anai.2025.06.004
Long-term safety and efficacy of once-daily berotralstat in patients with hereditary angioedema: APeX-S final results
Abstract
Background: Berotralstat is a once-daily oral medication for the prophylaxis of hereditary angioedema (HAE) attacks in patients aged 12 years and older.
Objective: To assess the long-term safety and efficacy of berotralstat in patients with HAE caused by C1 inhibitor deficiency.
Methods: APeX-S was a global, open-label phase 2 study (NCT03472040) assessing berotralstat 150 and 110 mg for up to 96 weeks in the United States and 240 weeks elsewhere. The primary objective was long-term safety and tolerability; secondary objectives included efficacy and impact on quality of life (QoL) of berotralstat. Safety was evaluated by means of treatment-emergent adverse events and laboratory analyses. Efficacy was assessed using the number and rate of HAE attacks, durability of response, and number and proportion of days with angioedema symptoms. QoL was evaluated using the Angioedema Quality of Life Questionnaire.
Results: In APeX-S, 387 patients were enrolled and received berotralstat 150 mg (n = 287) or 110 mg (n = 100) from day 1. A total of 70 patients on berotralstat 110 mg crossed over to berotralstat 150 mg after a median (range) of 48 (46-71) weeks. Treatment-emergent adverse events up to 240 weeks were reported by 334 patients (86.3%); the most common being nasopharyngitis (23.8%), headache (14.7%), diarrhea (14.5%), upper respiratory tract infection (12.9%), and abdominal pain (11.1%). Treatment with berotralstat led to improvements in HAE attack rates and Angioedema Quality of Life Questionnaire scores up to week 96, with greater improvements observed in patients who received berotralstat 150 mg from day 1.
Conclusion: This study supports the long-term safety of berotralstat and its efficacy in preventing HAE attacks and improving QoL.
Clinical trial registration: This trial was registered at ClinicalTrials.gov as NCT03472040 (https://clinicaltrials.gov/study/NCT03472040).
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Disclosures J Anderson is a speaker bureau member for BioCryst, CSL Behring, Pharming, and Takeda; has received consulting fees from BioCryst, CSL Behring, Cycle, Ionis, Pharming, Pharvaris, and Takeda; and is a clinical trial investigator or on the data safety monitoring committee for Astria, BioCryst, BioMarin, CSL Behring, KalVista, Pharvaris, and Takeda. E Aygören-Pürsün has received research grants from CSL Behring and Takeda; consulting fees from Astria, BioCryst, KalVista, and Intellia; and honoraria from Astria, BioCryst, CSL Behring, KalVista, Otsuka, Pharvaris, and Takeda. A Banerji has received research grant support from Astria and Ionis, and has provided consulting services to ADARx, Astria, BioCryst, CSL Behring, Intellia, Ionis, KalVista, Pharvaris, and Takeda. H Farkas has received honoraria/was an advisor for Astria, BioCryst, CSL Behring, KalVista, Intellia, Ionis, ONO Pharmaceutical, Pharming, Pharvaris, and Shire/Takeda; and received research grant support from CSL Behring, Pharming, and Shire/Takeda. M Jeseňák is or recently was an advisor and/or speaker and/or has received research or traveling grants from BioCryst, CSL Behring, KalVista, Pharming, Sobi, and Takeda. A Kessel has received honoraria as an advisor from BioCryst, Ionis, KalVista, Pharming, Pharvaris, and Shire/Takeda; and received research grant support from Shire/Takeda. S Kiani-Alikhan has received honoraria for consulting work and advisory board support and was Chief and Principal Investigator for studies organized by Astria, BioCryst, Biotest, CSL Behring, Ionis, KalVista, Pharvaris, Shire/Takeda, and X4 Pharmaceuticals. T Kinaciyan is or recently was an advisor and/or speaker and/or has received research funding from BioCryst, Blueprint Medicines, CSL Behring, Hal Allergy, KalVista, Kiniksa Pharmaceuticals, Novartis, Pharvaris, Sanofi-Aventis, and Takeda/Shire. M Manning has been a speaker/consultant for BioCryst, BioMarin, CSL Behring, Ionis, KalVista, Pharming, Pharvaris, and Takeda; and received research funding from Astria, BioCryst, BioMarin, CSL Behring, Ionis, KalVista, Pharvaris, and Takeda. JG Peter is or recently was an advisor and/or speaker for Astria, CSL Behring, KalVista, Pharvaris, and Takeda. A Reshef received research grants as a principal investigator, speaker, and advisor for BioCryst, CSL Behring, Ionis, Pharming, Pharvaris, and Takeda/Shire. M Stobiecki is or recently was an advisor and/or speaker for BioCryst, CSL Behring, KalVista, Pharvaris, Pharming, and Takeda. A Wu received medical writing support from BioCryst for the development of this article; and is the Director of Ksena Healthcare Ltd. HA Iocca, DT Johnston, and L Noble are employees of BioCryst Pharmaceuticals, Durham, North Carolina. D Tomita is a former employee of BioCryst Pharmaceuticals, Durham, North Carolina. D Hagin has no conflicts of interest to report.
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