eng Oriental Scientific Publishing Company Biosciences Biotechnology Research Asia 0973-1245 2025-12-30 22 4 1325 1336 10.13005/bbra/3444 57047 article Vikrant Dandekar 1 Milind Sathe 2 Department of Pharmaceutical Chemistry, Bharati Vidyapeeth's College of Pharmacy, C.B.D. Belapur, Navi-Mumbai, Mumbai University, Maharashtra, India 2Department of Pharmaceutical Sciences, Pharmaceutical Research and Development Consultant, Mumbai, Maharashtra, India Hereditary angioedema (HAE) is a rare, potentially life-threatening disorder caused by excessive bradykinin generation. Current injectable on-demand therapies may delay timely treatment during attacks. This review summarizes the discovery, mechanism, and clinical development of sebetralstat (KVD900), the first oral plasma kallikrein inhibitor for acute HAE. Literature from 2010–2025 was evaluated across major databases and regulatory sources, with emphasis on phase 3 KONFIDENT trial outcomes. Sebetralstat consistently reduced time to symptom relief (median 1.6–1.8 h vs 6.7 h with placebo) and demonstrated favorable tolerability with predominantly mild, transient adverse events. FDA and MHRA approvals in 2025 position sebetralstat as a patient-centered, self-administered option offering rapid, effective treatment at attack onset. Remaining needs include pediatric evaluation, real-world cost-effectiveness, and assessment of its potential role beyond acute therapy. https://www.biotech-asia.org/vol22no4/sebetralstat-first-oral-plasma-kallikrein-inhibitor-for-acute-hereditary-angioedema/ Hereditary angioedema; Kallikrein inhibitor; On-demand therapy; Plasma kallikrein; Regulatory approval; Sebetralstat