Long-Term Safety and Effectiveness of Sebetralstat: Interim Analysis of KONFIDENT-S Open-label Extension
Year: 2025
Type: article
Abstract: BACKGROUND: Poor compliance with hereditary angioedema guidelines for on-demand treatment is common due to challenges with parenteral administration. Sebetralstat, an oral plasma kallikrein inhibitor, demonstrated faster times to beginning of symptom relief, reduction in attack severity, and complete resolution than placebo in the phase 3 KONFIDENT trial (NCT05259917). OBJECTIVE: This analysis evaluated long-term safety and effectiveness of sebetralstat in KONFIDENT-S (NCT05505916), an ongoing, 2-year, open-label extension study. METHODS: Enrolled participants aged ≥12 years with hereditary angioedema due to C1-inhibitor deficiency administered sebetralstat 600 mg for each attack, as early as possible, regardless of severity or location. The primary outcome was incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes were times to beginning of symptom relief, reduction in severity, and complete resolution. RESULTS: At data cutoff (January 31, 2024), 84 participants (mean age: 35.9 years; 14.3% <18 years; 64.3% female) treated 640 attacks with sebetralstat (84% of total attacks); the median (interquartile range [IQR]) number of attacks per participant was 5 (2-8). The median (IQR) time from attack onset to treatment was 9 (1-69) minutes. Baseline severity was as follows: 30.0% mild, 43.3% moderate, and 25.0% severe or very severe. Treatment-related TEAEs occurred in 8 participants (9.5%); none were serious. The median time to beginning of symptom relief (allowing for missing data entries between consecutive time points) was 1.68 (0.79-3.89) hours, to reduction in severity 6.57 (1.61 to >12) hours, and to complete attack resolution 21.02 (7.22 to >24) hours. No evidence of a diminished response over repeated treatments of attacks was observed. CONCLUSIONS: Oral sebetralstat enabled compliance with treatment guidelines. No new safety signals were observed, and effectiveness for repeated attacks was consistent with the KONFIDENT trial results.
Authors: Henriette Farkas, John Anderson, Laurence Bouillet, Teresa Caballero, Mauro Cancian, Timothy Craig, Atsushi Fukunaga, Vesna Grivcheva-Panovska, Mar Guilarte, Daisuke Honda, Henry Kanarek, Sorena Kiani-Alikhan, Tamar Kinaciyan, Damia Leguevaques, Hilary J. Longhurst, Markus Magerl, Michael E. Manning, Inmaculada Martinez-Saguer, Isaac Melamed, Maeve E. O’Connor, Jonny Peter, Sinisa Savic, Daniel F. Soteres, Maria Staevska, Petra Staubach, Marcin Stobiecki, Raffi Tachdjian, Anna Valerieva, Patrick F.K. Yong, James Hao, Matthew Iverson, Michael D. Smith, Christopher M. Yea, Paul K. Audhya, Emel Aygören-Pürsün, Jonathan A. Bernstein, Danny M. Cohn, William R. Lumry, Marc A. Riedl, Andrea Zanichelli, Marcus Maurer
Institutions: Semmelweis University, Centre National de la Recherche Scientifique, Centre Hospitalier Universitaire de Grenoble, Translational Innovation in Medicine and Complexity, Université Grenoble Alpes, Hospital Universitario La Paz, Hospital La Paz Institute for Health Research, Centre for Biomedical Network Research on Rare Diseases, University of Padua, Pennsylvania State University, Vinmec Times City International Hospital, VinUniversity, Vinmec - VinUni Institute of Immunology, Osaka Medical and Pharmaceutical University, Ss. Cyril and Methodius University in Skopje, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Chiba University Hospital, University College London, Medical University of Vienna, Centre Hospitalier Universitaire de Lille, University of Auckland, Auckland City Hospital, Humboldt-Universität zu Berlin, Fraunhofer Institute for Translational Medicine and Pharmacology, Charité – Universitätsmedizin Berlin, University of Arizona College of Medicine- Phoenix, IMMUNOe Research Center, University of Cape Town, Groote Schuur Hospital, University of Leeds, Alexandrovska Hospital, Medical University of Sofia, University Medical Center of the Johannes Gutenberg University Mainz, Jagiellonian University, University of California, Los Angeles, Saint John's Health Center, Frimley Health NHS Foundation Trust, KalVista Pharmaceuticals (United States), Goethe University Frankfurt, University Hospital Frankfurt, Bernstein Clinical Research Center, University of Cincinnati, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, University of Amsterdam, University of California San Diego, University of Milan, IRCCS Policlinico San Donato
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,000
Funder: KalVista Pharmaceuticals
OpenAlex ID: W4413847656