Clinical Experience with Berotralstat in Patients with Hereditary Angioedema with Normal C1-Esterase Inhibitor: A Commented Case Series

Abstract

Hereditary angioedema (HAE) is a rare genetic disorder characterized by potentially life-threatening episodes of swelling. Most HAE cases are caused by deficient (type I) or dysfunctional (type II) C1-esterase inhibitor (C1-INH) protein. However, some patients present with a subtype of HAE that is associated with normal plasma levels of functional C1-INH protein and complement component 4 (HAE-nC1INH). Treatment of HAE-nC1INH is driven by clinical experience as robust clinical trial data to inform treatment decisions are lacking in this population. This retrospective case series assessed clinical features and treatment outcomes in 15 patients with HAE-nC1INH who initiated long-term prophylaxis with oral berotralstat 150 mg once daily as part of their disease management pathway. Most patients were female (93%), with a median age of 49 years. All patients experienced abdominal swelling attacks. On average, patients tried a mean of 4 different treatments for their HAE, including berotralstat. Although most patients associated prophylactic and on-demand medications that target the bradykinin pathway with improvements in the frequency and/or severity of attacks, treatment outcomes varied considerably between patients, highlighting the importance of a personalized approach to disease management. In this case series, berotralstat was an effective prophylactic treatment option in most patients with HAE-nC1INH. Further studies are required to demonstrate the potential efficacy, safety, and impact on quality of life of currently approved HAE therapies in patients with HAE-nC1INH.

Keywords:

• hereditary angioedema
• normal C1-esterase inhibitor
• prophylaxis
• berotralstat
• lanadelumab
• plasma-derived C1-esterase inhibitor
• abortive therapy

Abbreviations

HAE, hereditary angioedema; C1-INH, C1-esterase inhibitor; C4, complement component 4; CSU, chronic spontaneous urticaria; HAE-C1INH, HAE due to deficiency/defect in C1-INH; HAE-nC1INH, HAE with normal C1-esterase inhibitor and complement component 4; FDA, Food and Drug Administration; pdC1-INH, plasma-derived C1-esterase inhibitor; rhC1-INH, recombinant C1-esterase inhibitor; QID, four times daily.

Data Sharing Statement

The data supporting the conclusions of this manuscript are included within.

Ethics Approval and Informed Consent

This report describes a retrospective patient case series using anonymized data. Patients provided written informed consent for their de-identified case details to be collected, and all data was maintained with confidentiality. IRB review and approval was not sought for this research. This research was exempt from IRB review as it was a retrospective, longitudinal case review and involved an FDA approved medication for standard of care practice and these patients were treated as such.

Consent for Publication

Written informed consent was obtained from the patients for the publication of this case series.

Acknowledgments

The authors would like to thank the patients who contributed to this case series. Medical writing support was provided by Porterhouse Medical Group under the direction of the authors and in line with the GPP 2022 guidelines.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

HJK is a speaker for AstraZeneca plc, BioCryst Pharmaceuticals, Inc., Pharming Group N.V., and Teva Pharmaceuticals Industries Ltd., and has contracted research with ADMA Biologics, Inc., BioCryst Pharmaceuticals, Inc., BioMarin Pharmaceutical, Inc., Kedrion Biopharma, Inc., Novartis AG, Octapharma AG, Regeneron Pharmaceuticals, Inc., and Takeda Pharmaceutical Company Ltd. DASM has contract research with ADMA Biologics, Inc., BioCryst Pharmaceuticals, Inc., BioMarin Pharmaceutical, Inc., Kedrion Biopharma, Inc., Novartis AG, Octapharma AG, Regeneron Pharmaceuticals, Inc., and Takeda Pharmaceutical Company Ltd. The authors report no other conflicts of interest in this work.

Additional information

Funding

Development of this manuscript, writing support, and manuscript submission were funded by BioCryst Pharmaceuticals, Inc. BioCryst did not play a role in the design of the study nor the collection, analysis, and interpretation of data.