Ekterly (Sebetralstat): A First in Class Oral On Demand Treatment for Hereditary Angioedema

Authors

  • Hitanshi Nareshkumar Panchal GMERS Medical College, Gotri, Gujarat
  • Srijamya

DOI:

https://doi.org/10.5195/ijms.2025.4032

Keywords:

Bradykinin, Hereditary angioedema, On-demand therapy

Abstract

Background: Hereditary angioedema (HAE) is a rare, potentially life-threatening genetic disorder characterized by recurrent episodes of edema affecting the skin, gastrointestinal tract, and airway. With a prevalence of only about 0.0012% globally (range 0.0007–0.01%), its rarity contributes to frequent delays in diagnosis and treatment, increasing risk of severe complications. Until recently, on-demand therapies for HAE required intravenous or subcutaneous administration, limiting accessibility and adherence.

 

Objective: This study evaluates the clinical significance, therapeutic efficacy, and potential impact of Sebetralstat (Ekterly), the first FDA-approved oral on-demand therapy for HAE.

 

Methodology: A review of recent clinical trials was conducted, assessing efficacy and safety with key parameters including symptom relief time and bradykinin levels.

 

Discussion: Sebetralstat is a selective plasma kallikrein inhibitor that blocks bradykinin production, the central mediator of swelling in HAE. By reducing bradykinin, it prevents excessive vascular leakage responsible for symptoms. Clinical trials demonstrated rapid relief, with a median improvement time of 1.6 hours and some patients responding within 10 minutes. In laryngeal attacks, pooled analysis showed symptom relief within a median of 1.07 hours and complete resolution within 24 hours in 64.3% of cases, especially critical outcome to prevent airway obstruction. The oral formulation provides a practical alternative to injectables, enabling timely, unobtrusive treatment and improved quality of life.

 

Conclusion: Sebetralstat marks a breakthrough in HAE therapy, combining convenience, rapid action, and favorable safety. Its availability is expected to enhance compliance, empower patients, and redefine standards of care.

References

Davie RL, Edwards HJ, Evans DM, et al. Sebetralstat (KVD900): A potent and selective small molecule plasma kallikrein inhibitor featuring a novel P1 group as a potential oral on-demand treatment for hereditary angioedema. J Med Chem. 2022;65(21):14421-14438. doi:10.1021/acs.jmedchem.2c00921. PMID: 36251573; PMCID: PMC9620001.

Aygören-Pürsün E, Zanichelli A, Cohn DM, et al. An investigational oral plasma kallikrein inhibitor for on-demand treatment of hereditary angioedema: a two-part, randomised, double-blind, placebo-controlled, crossover phase 2 trial. Lancet. 2023;401(10381):879-889. doi:10.1016/S0140-6736(22)02406-0

Riedl MA, Farkas H, Aygören-Pürsün E, Psarros F, Soteres DF, Staevska M, Cancian M, et al. Oral sebetralstat for on-demand treatment of hereditary angioedema attacks. N Engl J Med. 2024;391(1):32-43. doi:10.1056/NEJMoa2314192

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Published

2025-12-31

How to Cite

Hitanshi Nareshkumar Panchal, & Srijamya. (2025). Ekterly (Sebetralstat): A First in Class Oral On Demand Treatment for Hereditary Angioedema. International Journal of Medical Students, 13, S252. https://doi.org/10.5195/ijms.2025.4032

Issue

Vol 13. (2025): Supplement 1

Section

Abstracts of the WCMSR

Categories

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Copyright (c) 2025 Hitanshi Nareshkumar Panchal, Srijamya

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