{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T12:30:54Z","timestamp":1791549054644,"version":"4.3.4"},"reference-count":25,"publisher":"American Society of Hematology","issue":"13","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,7,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>PUPs B-LONG evaluated the safety and efficacy of recombinant factor IX Fc fusion protein (rFIXFc) in previously untreated patients (PUPs) with hemophilia B. In this open-label, phase 3 study, male PUPs (age &amp;lt;18 years) with hemophilia B (\u22642 IU\/dL of endogenous factor IX [FIX]) were to receive treatment with rFIXFc. Primary end point was occurrence of inhibitor development, with a secondary end point of annualized bleed rate (ABR). Of 33 patients who received \u22651 dose of rFIXFc, 26 (79%) were age &amp;lt;1 year at study entry and 6 (18%) had a family history of inhibitors. Twenty-eight patients (85%) received prophylaxis; median dosing interval was 7 days, with an average weekly dose of 58 IU\/kg. Twenty-seven patients (82%) completed the study. Twenty-one (64%), 26 (79%), and 28 patients (85%) had \u226550, \u226520, and \u226510 exposure days (EDs) to rFIXFc, respectively. One patient (3.03%; 95% confidence interval, 0.08% to 15.76%) developed a low-titer inhibitor after 11 EDs; no high-titer inhibitors were detected. Twenty-three patients (70%) had 58 treatment-emergent serious adverse events; 2 were assessed as related (FIX inhibition and hypersensitivity in 1 patient, resulting in withdrawal). Median ABR was 1.24 (interquartile range, 0.00-2.49) for patients receiving prophylaxis. Most (&amp;gt;85%) bleeding episodes required only 1 infusion for bleed resolution. In this first study reporting results with rFIXFc in pediatric PUPs with hemophilia B, rFIXFc was well tolerated, with the adverse event profile as expected in a pediatric hemophilia population. rFIXFc was effective, both as prophylaxis and in the treatment of bleeding episodes. This trial was registered at www.clinicaltrials.gov as #NCT02234310.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020004085","type":"journal-article","created":{"date-parts":[[2021,7,10]],"date-time":"2021-07-10T05:04:31Z","timestamp":1625893471000},"page":"2732-2739","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":27,"title":["Final results of the PUPs B-LONG study: evaluating safety and efficacy of rFIXFc in previously untreated patients with hemophilia B"],"prefix":"10.1182","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0145-4736","authenticated-orcid":false,"given":"Beatrice","family":"Nolan","sequence":"first","affiliation":[{"name":"Children\u2019s Health Ireland at Crumlin, Dublin, Ireland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Klukowska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hematology and Oncology, Medical University of Warsaw, Warsaw, Poland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Indiana Hemophilia and Thrombosis Center, Indianapolis, IN;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1182-4131","authenticated-orcid":false,"given":"Antoine","family":"Rauch","sequence":"additional","affiliation":[{"name":"Department of Hematology and Transfusion, Centre Hospitalier Universitaire de Lille, Lille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2805-1016","authenticated-orcid":false,"given":"Michael","family":"Recht","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Pediatrics, Oregon Health & Science University, Portland, OR;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Ragni","sequence":"additional","affiliation":[{"name":"University of Pittsburgh Medical Center, Pittsburgh, PA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Curtin","sequence":"additional","affiliation":[{"name":"The Children\u2019s Hospital at Westmead, Westmead, NSW, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sriya","family":"Gunawardena","sequence":"additional","affiliation":[{"name":"Sanofi, Waltham, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sutirtha","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Sanofi, Ghent, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepthi","family":"Jayawardene","sequence":"additional","affiliation":[{"name":"Sanofi, Waltham, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bent","family":"Winding","sequence":"additional","affiliation":[{"name":"Sobi, Stockholm, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7126-6613","authenticated-orcid":false,"given":"Kathelijn","family":"Fischer","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht, Utrecht, The Netherlands; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raina","family":"Liesner","sequence":"additional","affiliation":[{"name":"Great Ormond Street Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2021,7,9]]},"reference":[{"issue":"8","key":"2021070922551991700_B1","doi-asserted-by":"crossref","first-page":"540","DOI":"10.7326\/M19-1208","article-title":"Establishing the prevalence and prevalence at birth of hemophilia in males: a meta-analytic approach using national registries","volume":"171","author":"Iorio","year":"2019","journal-title":"Ann Intern Med."},{"issue":"8","key":"2021070922551991700_B2","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1080\/17474086.2018.1489719","article-title":"The benefits of prophylaxis in patients with hemophilia B","volume":"11","author":"Castaman","year":"2018","journal-title":"Expert Rev Hematol."},{"issue":"5","key":"2021070922551991700_B3","first-page":"378","article-title":"Intracranial haemorrhage in children and adults with haemophilia A and B: a literature review of the last 20 years","volume":"17","author":"Zanon","year":"2019","journal-title":"Blood Transfus."},{"issue":"1","key":"2021070922551991700_B4","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1055\/s-0031-1300954","article-title":"Prophylaxis in children with hemophilia: evidence-based achievements, old and new challenges","volume":"38","author":"Coppola","year":"2012","journal-title":"Semin Thromb Hemost."},{"issue":"3","key":"2021070922551991700_B5","first-page":"314","article-title":"Achieving and maintaining an optimal trough level for prophylaxis in haemophilia: the past, the present and the future","volume":"12","author":"Jim\u00e9nez-Yuste","year":"2014","journal-title":"Blood Transfus."},{"issue":"26","key":"2021070922551991700_B6","doi-asserted-by":"crossref","first-page":"3880","DOI":"10.1182\/blood-2014-05-573055","article-title":"Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial","volume":"124","author":"Collins","year":"2014","journal-title":"Blood."},{"issue":"24","key":"2021070922551991700_B7","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1056\/NEJMoa1305074","article-title":"Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B","volume":"369","author":"Powell","year":"2013","journal-title":"N Engl J Med."},{"issue":"14","key":"2021070922551991700_B8","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1182\/blood-2015-09-669234","article-title":"Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial","volume":"127","author":"Santagostino","year":"2016","journal-title":"Blood."},{"issue":"9","key":"2021070922551991700_B9","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1517\/14712598.2013.819339","article-title":"Development of long-acting recombinant FVIII and FIX Fc fusion proteins for the management of hemophilia","volume":"13","author":"Shapiro","year":"2013","journal-title":"Expert Opin Biol Ther."},{"key":"2021070922551991700_B10","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.1182\/blood-2019-131185","article-title":"How caring for toddlers and young children with severe haemophilia impacts on caregiver\u2019s burden [abstract]","volume":"134","author":"Halimeh","year":"2019","journal-title":"Blood."},{"key":"2021070922551991700_B11","volume-title":"Treatment of Hemophilia. No. 7. Inhibitors in Hemophilia: A Primer.","author":"Carcao","year":"2018"},{"issue":"1","key":"2021070922551991700_B12","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3324\/haematol.2019.239160","article-title":"Inhibitor incidence in an unselected cohort of previously untreated patients with severe haemophilia B: a PedNet study","volume":"106","author":"Male","year":"2021","journal-title":"Haematologica."},{"key":"2021070922551991700_B13","year":"2020"},{"issue":"10","key":"2021070922551991700_B14","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1182\/blood-2009-08-239665","article-title":"Prolonged activity of factor IX as a monomeric Fc fusion protein","volume":"115","author":"Peters","year":"2010","journal-title":"Blood."},{"issue":"7","key":"2021070922551991700_B15","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nrd.2018.70","article-title":"Advances and innovations in haemophilia treatment","volume":"17","author":"Peters","year":"2018","journal-title":"Nat Rev Drug Discov."},{"issue":"2","key":"2021070922551991700_B16","doi-asserted-by":"crossref","first-page":"e75","DOI":"10.1016\/S2352-3026(16)30193-4","article-title":"Recombinant factor IX Fc fusion protein in children with haemophilia B (Kids B-LONG): results from a multicentre, non-randomised phase 3 study","volume":"4","author":"Fischer","year":"2017","journal-title":"Lancet Haematol."},{"issue":"6","key":"2021070922551991700_B17","doi-asserted-by":"crossref","first-page":"e262","DOI":"10.1111\/hae.14036","article-title":"Long-term safety and sustained efficacy for up to 5 years of treatment with recombinant factor IX Fc fusion protein in subjects with haemophilia B: Results from the B-YOND extension study","volume":"26","author":"Pasi","year":"2020","journal-title":"Haemophilia."},{"issue":"7","key":"2021070922551991700_B18","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1111\/jth.12276","article-title":"An interactive mutation database for human coagulation factor IX provides novel insights into the phenotypes and genetics of hemophilia B","volume":"11","author":"Rallapalli","year":"2013","journal-title":"J Thromb Haemost."},{"issue":"7","key":"2021070922551991700_B19","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1002\/rth2.12412","article-title":"Nonacog beta pegol (N9-GP) in hemophilia B: first report on safety and efficacy in previously untreated and minimally treated patients","volume":"4","author":"Chan","year":"2020","journal-title":"Res Pract Thromb Haemost."},{"issue":"2","key":"2021070922551991700_B20","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1182\/blood-2004-06-2283","article-title":"The safety and efficacy of recombinant human blood coagulation factor IX in previously untreated patients with severe or moderately severe hemophilia B","volume":"105","author":"Shapiro","year":"2005","journal-title":"Blood."},{"issue":"1","key":"2021070922551991700_B21","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/j.1365-2516.2008.01880.x","article-title":"The North American Immune Tolerance Registry: contributions to the thirty-year experience with immune tolerance therapy","volume":"15","author":"DiMichele","year":"2009","journal-title":"Haemophilia."},{"issue":"3","key":"2021070922551991700_B22","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/j.1365-2141.2007.06657.x","article-title":"Inhibitor development in haemophilia B: an orphan disease in need of attention","volume":"138","author":"DiMichele","year":"2007","journal-title":"Br J Haematol."},{"key":"2021070922551991700_B23","first-page":"S125","article-title":"Development of anaphylactic shock in haemophilia B patients with inhibitors","volume":"9","author":"Warrier","year":"1998","journal-title":"Blood Coagul Fibrinolysis."},{"issue":"3","key":"2021070922551991700_B24","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1182\/blood-2011-07-367003","article-title":"Recombinant factor IX-Fc fusion protein (rFIXFc) demonstrates safety and prolonged activity in a phase 1\/2a study in hemophilia B patients","volume":"119","author":"Shapiro","year":"2012","journal-title":"Blood."},{"issue":"3","key":"2021070922551991700_B25","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1160\/TH16-05-0398","article-title":"Long-term safety and efficacy of extended-interval prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) in subjects with haemophilia B","volume":"117","author":"Pasi","year":"2017","journal-title":"Thromb Haemost."}],"container-title":["Blood Advances"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/5\/13\/2732\/1813552\/advancesadv2020004085.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/5\/13\/2732\/1813552\/advancesadv2020004085.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,10]],"date-time":"2021-07-10T05:04:52Z","timestamp":1625893492000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article\/5\/13\/2732\/476278\/Final-results-of-the-PUPs-B-LONG-study-evaluating"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,9]]},"references-count":25,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2021,7,13]]}},"URL":"https:\/\/doi.org\/10.1182\/bloodadvances.2020004085","relation":{},"ISSN":["2473-9529","2473-9537"],"issn-type":[{"value":"2473-9529","type":"print"},{"value":"2473-9537","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,9]]}}}