Efficacy and Safety of NTQ5082 in Complement Inhibitor‐Naïve Patients With Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematologic disorder characterized by complement-mediated intravascular hemolysis, pancytopenia, and thrombosis. NTQ5082 is a novel oral selective complement factor B (CFB) inhibitor that suppresses alternative pathway activity, thereby inhibiting intravascular hemolysis in PNH. We conducted a randomized, open-label Phase 2 study to investigate NTQ5082 monotherapy in adults with PNH who had not previously received complement inhibitors. Twenty-five patients were assigned to receive oral NTQ5082 once daily (QD) at 100 mg (group A) or 200 mg (group B) for 12 weeks. In both groups, lactate dehydrogenase (LDH) levels rapidly decreased, and hemoglobin (Hb) levels increased within 1 week after treatment initiation, with no further transfusions needed. At week 12, the mean LDH concentration was 239.4 ± 63.5 U/L in group A and 245.8 ± 72.6 U/L in group B. The Hb concentration increased to ≥ 20 g/L from baseline in 100% of patients, while 50% and 61.5% of patients in groups A and B, respectively, achieved Hb concentrations ≥ 120 g/L. The most frequently reported treatment-related adverse events (TRAEs) were headache (12%), upper respiratory tract infection (8%), and decreased neutrophil count (8%); no grade ≥ 3 adverse events (AEs) were reported. Oral NTQ5082 administered at 100 or 200 mg QD effectively controlled hemolysis, significantly increased Hb levels, and improved quality of life, with a satisfactory safety profile, suggesting that NTQ5082 may represent a promising therapeutic option for complement inhibitor-naïve patients with PNH.