Pozelimab

CD55-deficient protein-losing enteropathy (PLE), or CHAPLE disease, is an ultra-rare hereditary disease, with fewer than 100 patients diagnosed worldwide or fewer than 10 patients in the US. The pathophysiology of this disease is mainly attributed to the deficiency of the CD55 protein, which is the main regulator of the complement cascade.. Under normal circumstances, CD55 inhibits the activity of C3 and C5 convertases, thus preventing the cleavage of C3 and C5 respectively into immunoreactive peptides C3a and C5a. The loss of CD55 can therefore induce complement hyperactivation, causing the unwanted formation of membrane-attacking complex and resulting in paroxysmal nocturnal hemoglobinuria and complement-mediated autoimmune hemolysis that are often observed in CHAPLE disease.

Pozelimab is a human, monoclonal immunoglobulin G4 antibody against the terminal complement protein C5. In August 18, 2023, pozelimab was approved by the FDA for the treatment of CHAPLE disease. It is currently the only treatment explicitly indicated for CHAPLE disease.