{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T07:40:09Z","timestamp":1756366809929,"version":"3.44.0"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018731","name":"Jiangsu Hengrui Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, life\u2010threatening disorder characterized by complement\u2010mediated haemolysis, leading to anaemia and thrombosis. HRS\u20105965 is a novel, oral, selective complement factor B inhibitor targeting the alternative pathway, potentially reducing both intra\u2010 and extravascular haemolysis. In this randomized, open\u2010label phase II study, we evaluated the efficacy and safety of HRS\u20105965 monotherapy in complement inhibitor\u2013na\u00efve adult PNH patients. Twenty\u2010six patients were randomized 1:1 to receive HRS\u20105965 50\u2009mg orally twice daily (BID) (with potential up\u2010titration to 100\u2009mg BID) or 75\u2009mg BID for 12\u2009weeks. The primary end\u2010point 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\u2009g\/L for the 50 and 75\u2009mg BID groups respectively. Lactate dehydrogenase levels declined by 87% and 85% from baseline. The most common treatment\u2010related adverse events were mild lab abnormalities, including increased alkaline phosphatase and alanine aminotransferase. In conclusion, HRS\u20105965 monotherapy at either 50 or 75\u2009mg 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\u2013na\u00efve PNH patients.<\/jats:p>","DOI":"10.1111\/bjh.20230","type":"journal-article","created":{"date-parts":[[2025,7,13]],"date-time":"2025-07-13T12:22:17Z","timestamp":1752409337000},"page":"571-581","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of <scp>HRS<\/scp>\u20105965 monotherapy in complement inhibitor\u2013na\u00efve patients with paroxysmal nocturnal haemoglobinuria"],"prefix":"10.1111","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4702-9658","authenticated-orcid":false,"given":"Li","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Hu","sequence":"additional","affiliation":[{"name":"Clinical Research and Development Jiangsu Hengrui Pharmaceuticals Co Ltd  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Huang","sequence":"additional","affiliation":[{"name":"Clinical Research and Development Jiangsu Hengrui Pharmaceuticals Co Ltd  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"Shu","sequence":"additional","affiliation":[{"name":"Clinical Research and Development Jiangsu Hengrui Pharmaceuticals Co Ltd  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengkui","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases 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