Abstract
Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder caused by PIGA mutations leading to deficiency of GPI-anchored proteins (CD55/CD59), resulting in complement-mediated hemolysis. Iptacopan, an oral factor B inhibitor, acts by blocking C3 convertase in the alternative complement pathway.
Aims: To evaluate the real-world efficacy and safety of iptacopan in PNH patients.
Methods: We retrospectively analyzed 20 PNH patients treated with iptacopan across four Chinese centers (2024-2025), including 10 with classic PNH, 9 with PNH-aplastic anemia (PNH-AA), and 1 with PNH-myelodysplastic syndrome (PNH-MDS). Hematologic response, symptom relief, and adverse events (AEs) were assessed.
Results: The study cohort (N=20) had a median age of 42 years (range 20-74) with 45% (9/20) male patients. Baseline assessments revealed severe disease manifestations: 35% (7/20) had hemoglobin (Hb) ≤ 60 g/L, 80% (16/20) showed lactate dehydrogenase (LDH) levels > 2 × upper limit of normal (ULN), 65% (13/20) had elevated total bilirubin (TBIL > ULN), and 45% (9/20) were transfusion-dependent. Treatment regimens included iptacopan monotherapy (200 mg bid) in 25% (5/20) and combination therapy (cyclosporine n=3, prednisone n=1) in 20% (4/20). At week 2 (n=7 evaluable), 71% (5/7) achieved ≥ 10 g/L Hb increase (including 4/5 with ≥ 20 g/L improvement), 42.8% (3/7) demonstrated ≥ 4 × LDH reduction, 57% (4/7) normalized TBIL, and 28.6% (2/7) showed ≥ 2-fold FACIT-Fatigue score improvement, with all patients achieving transfusion independence. By month 1 (n=10), responses deepened: 70% (7/10) attained ≥ 20 g/L Hb increase (including 3/7 ≥ 40 g/L), 80% (8/10) achieved ≥ 5 LDH reduction, all patients had normalized TBIL levels, and 30% (3/10) had improved FACIT-Fatigue scores ≥ 2-fold. Month 3 outcomes (n=8) showed sustained efficacy: 75% (6/8) maintained ≥ 20 g/L Hb improvement (4/6 ≥ 40 g/L), 87.5% (7/8) sustained ≥ 3 × LDH reduction, 75% (6/8) normalizing TBIL, and 25% (2/8) preserved ≥ 2-fold FACIT-Fatigue improvement, with no transfusion requirements in any patient. Adverse events occurred in 15% (3/20), manifesting as dark urine, Hb decline, and LDH elevation attributable to treatment interruption/non-adherence-induced hemolysis. No treatment discontinuations were required.
Conclusion: These real-world data demonstrate iptacopan's rapid efficacy in improving hematologic parameters, relieving fatigue, and achieving durable transfusion independence with favorable safety in PNH, though larger prospective studies are needed for validation. Further validation through extended follow-up and larger-scale studies is warranted.
Keywords: PNH, iptacopan, treatment
