Poster: CT-118: PH3 Study of Efficacy and Safety of Iptacopan (LNP023), an Oral Complement Factor B Inhibitor, in Patients with Paroxysmal Nocturnal Hemoglobinuria and Residual Anemia Despite Anti-C5 Antibody Treatment

Context The standard of care in PNH is anti-C5 monoclonal antibody (MAb) treatment with eculizumab (ECU) or ravulizumab (RAV), but hematological responses can be heterogenous. Iptacopan (LNP023) is a first-in-class, oral, small-molecule, selective and reversible complement factor B inhibitor that inhibits both intra- and extravascular hemolysis. In an ongoing Ph2 study (NCT03439839), iptacopan add-on treatment demonstrated improvements in hematological response and biomarkers of disease activity in adult PNH patients with active hemolysis despite ECU treatment. Objective APPLY-PNH (NCT04558918) will assess efficacy and safety of iptacopan monotherapy in adult PNH patients with residual anemia despite prior anti-C5 MAb treatment by evaluating its superiority to anti-C5 MAb treatment. Design The study comprises an ≤8-wk screening period; 24-wk, randomized, open label, active controlled, parallel group treatment period; and 24-wk treatment extension period. Patients (N≈91) are randomized (8:5) to iptacopan monotherapy 200mg orally BID (seamless switch from prior treatment) or intravenous ECU/RAV (continue prior treatment). Patients are stratified based on prior anti-C5 treatment and transfusion history. On completion of Wk 24 visit, patients may enter 24-wk iptacopan treatment extension. Eligible patients must have confirmed diagnosis of PNH (RBCs and WBCs [granulocyte/monocyte] clone size ≥10%) and residual anemia (mean Hb Conclusions This study will be the first head-to-head comparison of iptacopan vs an anti-C5 MAb in PNH patients. Study sponsored by Novartis Pharmaceuticals Corporation.