Factor B Inhibition with Oral Iptacopan Monotherapy Demonstrates Sustained Long-Term Efficacy and Safety in Anti-C5-Treated Patients (pts) with Paroxysmal Nocturnal Hemoglobinuria (PNH) and Persistent Anemia: Final 48-Week Results from the Multicenter, Phase III APPLY-PNH Trial

Drs Roeth and Kulasekararaj contributed equally as authors. Background: Iptacopan is the first oral complement inhibitor that acts proximally in the complement system to target factor B in the alternative pathway. Iptacopan has shown efficacy/safety in PNH pts with persistent anemia despite anti-C5 therapy and complement inhibitor-naive pts. In the Phase III APPLY-PNH trial (NCT04558918), iptacopan monotherapy led to clinically meaningful hemoglobin (Hb) increases and normal/near-normal Hb levels in a majority of pts, transfusion avoidance and improved pt-reported fatigue, showing superiority vs C5 inhibitors at Week (Wk) 24. Aim: We report the final APPLY-PNH data after a 24-wk extension period in which all pts received iptacopan monotherapy (study completion: 6 March 2023). Methods: Adult PNH pts (mean Hb