An evaluation of pozelimab for the treatment of CHAPLE disease.

Abstract

Introduction: CHAPLE disease is a severe, ultra-rare disorder caused by CD55 gene mutations, leading to uncontrolled complement hyperactivation, protein-losing enteropathy, and systemic thrombosis. Recent advances in targeted therapies, particularly the C5 inhibitor pozelimab (Veopoz), offer new treatment options by addressing complement dysregulation, marking a shift from symptomatic to precision therapy.

Areas covered: This review explores the pathophysiology, clinical manifestations, and current treatments for CHAPLE disease. It examines pozelimab's pharmacological development, its mechanism as a C5 inhibitor, and results from Phase 1 to Phase 3 studies. Additionally, potential use of other anti-C5 therapies and emerging agents targeting proximal complement components are discussed. A systematic literature search using PubMed, Google Scholar, and ClinicalTrials.gov focused on studies from 2017 onwards to provide a comprehensive overview.

Expert opinion: Managing CHAPLE disease requires a combination of targeted anti-complement therapies like pozelimab and supportive measures, including nutritional support and thrombosis management. While pozelimab shows promise in reversing core symptoms, risks like serious infections necessitate preventive measures, such as vaccination and antibiotic prophylaxis. Future research should focus on optimizing dosing, evaluating long-term safety, and assessing the need for lifelong therapy. Expanding our understanding of the disease's pathophysiology will refine treatment strategies and improve outcomes.