{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:57:08Z","timestamp":1790477828569,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra\u2010rare, life\u2010threatening disease associated with chronic intravascular hemolysis due to uncontrolled complement activation. PNH results in anemia with an increased risk of thrombosis, and often causes severe fatigue, and decreased physical function and health\u2010related quality of life (QoL). We investigated the efficacy, safety, and patient\u2010reported outcomes data of the combination of pozelimab (a fully human monoclonal antibody) and cemdisiran (an <jats:italic>N<\/jats:italic>\u2010acetylgalactosamine\u2010conjugated small interfering ribonucleic acid) from a Phase 2 trial (NCT04811716) in patients with PNH who transitioned from pozelimab monotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this randomized, open\u2010label, Phase 2 study, patients were randomized (1:1) to one of two treatment arms; both arms received subcutaneous cemdisiran 200\u00a0mg every 4 weeks (Q4W) plus subcutaneous pozelimab 400\u00a0mg either Q4W (Arm 1) or every 2 weeks (Arm 2).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010four patients were treated with combination dosing. During the 28\u2010week open\u2010label treatment period (OLTP), 20 patients (83.3%) maintained control of lactate dehydrogenase (\u2264 1.5 \u00d7 upper limit of normal) at all timepoints. The majority of patients (92%) did not require a blood transfusion. While most patients (66.7%) experienced treatment\u2010emergent adverse events, the majority of these events were mild to moderate in severity. No meningococcal infections, thrombotic events, or deaths were reported. The combination therapy maintained improvements in patient\u2010reported fatigue, physical functioning, and QoL throughout the OLTP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Combination treatment maintained adequate hemolysis control and was generally well tolerated. Administration of pozelimab Q2W did not improve disease control as compared to pozelimab Q4W.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>ClinicalTrials.gov\/NCT04811716<\/jats:p><\/jats:sec>","DOI":"10.1002\/jha2.70095","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T15:36:08Z","timestamp":1753371368000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Safety, Efficacy, and Patient\u2010Reported Outcomes From a Phase 2 Randomized Trial of Pozelimab and Cemdisiran Combination in Patients With Paroxysmal Nocturnal Hemoglobinuria"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7423-4676","authenticated-orcid":false,"given":"Jun\u2010Ho","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Hematology\u2010Oncology Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond Siu Ming","family":"Wong","sequence":"additional","affiliation":[{"name":"Sir Y.K. Pao Centre for Cancer and Department of Medicine &amp; Therapeutics Prince of Wales Hospital The Chinese University of Hong Kong Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Hartford","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc. Sleepy Hollow New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Pavani","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc. Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Aurand","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc. Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quang","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc. Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosalai","family":"Mohan","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc. Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karoline","family":"Meagher","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc. Sleepy Hollow New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Sherman","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc. Sleepy Hollow New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Rofail","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc. Sleepy Hollow New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorah","family":"Perlee","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc. Tarrytown New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Souttou","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc. 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