HRS-5965

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, life‐threatening disorder characterized by complement‐mediated haemolysis, leading to anaemia and thrombosis. HRS‐5965 is a novel, oral, selective complement factor B inhibitor targeting the alternative pathway, potentially reducing both intra‐ and extravascular haemolysis. In this randomized, open‐label phase II study, we evaluated the efficacy and safety of HRS‐5965 monotherapy in complement inhibitor–naïve adult PNH patients. Twenty‐six patients were randomized 1:1 to receive HRS‐5965 50 mg orally twice daily (BID) (with potential up‐titration to 100 mg BID) or 75 mg BID for 12 weeks. The primary end‐point was the change in haemoglobin (Hb) from baseline to Week 12. Both groups showed marked Hb increases, with least squares mean increases of 37.6 and 37.7 g/L for the 50 and 75 mg BID groups respectively. Lactate dehydrogenase levels declined by 87% and 85% from baseline. The most common treatment‐related adverse events were mild lab abnormalities, including increased alkaline phosphatase and alanine aminotransferase. In conclusion, HRS‐5965 monotherapy at either 50 or 75 mg BID resulted in substantial Hb improvements and reduced haemolysis with an acceptable safety profile, suggesting its potential as a promising oral therapy for complement inhibitor–naïve PNH patients.