Advances in treatments for hemophilia A/B with inhibitors: current treatment gaps and promising therapies

Abstract

INTRODUCTION: Hemophilia A and B are inherited bleeding disorders caused by deficiencies of coagulation factors VIII and IX. The development of neutralizing alloantibodies (inhibitors) remains the most serious treatment complication, rendering factor replacement ineffective and substantially increasing morbidity, treatment complexity, and healthcare costs. AREAS COVERED: A literature search was conducted using PubMed/MEDLINE, Embase, and Google Scholar for publications from January 2000 to March 2026 using combinations of the terms 'hemophilia A,' 'hemophilia B,' 'inhibitors,' 'immune tolerance induction,' 'bypassing agents,' 'emicizumab,' 'concizumab,' 'marstacimab,' 'fitusiran,' and 'gene therapy.' Relevant clinical trials, observational studies, guidelines, and review articles were evaluated. This review examines current and emerging therapies for inhibitor patients, including bypassing agents, immune tolerance induction, emicizumab, anti-tissue factor pathway inhibitor therapies, antithrombin suppression, next-generation factor mimetics, gene therapy, and immune-modulatory approaches. Pivotal clinical trials demonstrate major reductions in bleeding rates and significant advances in prophylactic care. EXPERT OPINION: Despite transformative progress, important unmet needs remain, including incomplete hemostatic control, lack of predictive biomarkers, limited laboratory standardization, and inequitable global access. Future advances will depend on biomarker-guided personalized therapy, rational combination strategies, and integration of immune-modulatory and gene-based approaches to achieve durable tolerance and potentially curative outcomes.