Evaluating pozelimab in the treatment of CHAPLE disease

CHAPLE disease (Complement Hyperactivation, Angiopathic Thrombosis, and Protein-Losing Enteropathy [PLE]) is a rare, life-threatening disorder caused by biallelic mutations in the <i>CD55</i> gene, which encodes decay-accelerating factor, a key regulator of the complement system. The disease typically manifests in early childhood with hypoalbuminemic edema, gastrointestinal symptoms, recurrent infections, and failure to thrive, alongside an elevated thrombotic risk due to complement-mediated endothelial injury and coagulation activation. Given these pathogenetic mechanisms, complement-targeted therapies have emerged as a rational approach to disease management. Eculizumab, a monoclonal antibody against complement component C5, initially demonstrated clinical benefit when administered on a compassionate-use basis. Building upon this success, pozelimab, a next-generation subcutaneous anti-C5 monoclonal antibody, was evaluated in CHAPLE patients and subsequently received U.S. FDA approval for this indication. Pozelimab effectively inhibits terminal complement activation, leading to sustained remission of PLE, obviating the need for albumin replacement, reducing hospitalization rates, improving symptom control and nutritional status, and ultimately enhancing overall quality of life. This review highlights the evolving role of pozelimab in CHAPLE disease by discussing its mechanistic basis, emerging clinical evidence, and implications for patient-centered care.