Oral Iptacopan Monotherapy: A New Frontier for Paroxysmal Nocturnal Hemoglobinuria

For paroxysmal nocturnal hemoglobinuria (PNH), the current standard of care (SOC) is intravenous treatment with monoclonal antibodies (eculizumab and ravulizumab) that block complement pathways through C5 inhibition. However, roughly 40% of patients continue to have chronic extravascular hemolysis due to ongoing activation of proximal complement pathways with C3 fragments. Iptacopan, an oral agent, inhibits factor B in the alternative complement pathway proximal to C5 generation, preventing C3-mediated hemolysis.

Two industry-sponsored, multicenter, phase 3 clinical trials evaluated the efficacy and safety of oral iptacopan (200 mg twice daily for 24 weeks) in adults with PNH. In the randomized, controlled APPLY-PNH trial, 97 patients who we…