{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:49:56Z","timestamp":1793321396998,"version":"4.5.0"},"reference-count":42,"publisher":"American Society of Hematology","issue":"14","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,4,4]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Subcutaneous emicizumab enables prophylaxis for people with hemophilia A (HA) from birth, potentially reducing risk of bleeding and intracranial hemorrhage (ICH). HAVEN 7 (NCT04431726) is the first clinical trial of emicizumab dedicated to infants, designed to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab in those aged \u226412 months with severe HA without factor VIII (FVIII) inhibitors. Participants in this phase 3b trial received emicizumab 3 mg\/kg maintenance dose every 2 weeks for 52 weeks and are continuing emicizumab during the 7-year long-term follow-up. Efficacy end points included annualized bleed rate (ABR): treated, all, treated spontaneous, and treated joint bleeds. Safety end points included adverse events (AEs), thromboembolic events (TEs), thrombotic microangiopathies (TMAs), and immunogenicity (anti-emicizumab antibodies [ADAs] and FVIII inhibitors). At primary analysis, 55 male participants had received emicizumab (median treatment duration: 100.3; range, 52-118 weeks). Median age at informed consent was 4.0 months (range, 9 days to 11 months 30 days). Model-based ABR for treated bleeds was 0.4 (95% confidence interval, 0.30\u20130.63), with 54.5% of participants (n\u00a0= 30) having zero treated bleeds. No ICH occurred. All 42 treated bleeds in 25 participants (45.5%) were traumatic. Nine participants (16.4%) had \u22651 emicizumab-related AE (all grade 1 injection-site reactions). No AE led to treatment changes. No deaths, TEs, or TMAs occurred. No participant tested positive for ADAs. Two participants were confirmed positive for FVIII inhibitors. This primary analysis of HAVEN 7 indicates that emicizumab is efficacious and well tolerated in infants with severe HA without FVIII inhibitors.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2023021832","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T17:26:56Z","timestamp":1703179616000},"page":"1355-1364","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":99,"title":["Emicizumab prophylaxis in infants with hemophilia A (HAVEN 7): primary analysis of a phase 3b open-label trial"],"prefix":"10.1182","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2558-2089","authenticated-orcid":false,"given":"Steven W.","family":"Pipe","sequence":"first","affiliation":[{"name":"1University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Collins","sequence":"additional","affiliation":[{"name":"2School of Medicine, Cardiff University, Cardiff, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Dhalluin","sequence":"additional","affiliation":[{"name":"3F. Hoffmann-La Roche Ltd, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gili","family":"Kenet","sequence":"additional","affiliation":[{"name":"4Sheba Medical Center, Ramat Gan, Israel"},{"name":"5Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Schmitt","sequence":"additional","affiliation":[{"name":"3F. Hoffmann-La Roche Ltd, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7432-4874","authenticated-orcid":false,"given":"Muriel","family":"Buri","sequence":"additional","affiliation":[{"name":"3F. Hoffmann-La Roche Ltd, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3937-3499","authenticated-orcid":false,"given":"V\u00edctor","family":"Jim\u00e9nez-Yuste","sequence":"additional","affiliation":[{"name":"6La Paz University Hospital-IdiPaz, Aut\u00f3noma University, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7423-9864","authenticated-orcid":false,"given":"Flora","family":"Peyvandi","sequence":"additional","affiliation":[{"name":"7Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy"},{"name":"8Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6013-1254","authenticated-orcid":false,"given":"Guy","family":"Young","sequence":"additional","affiliation":[{"name":"9Children\u2019s Hospital Los Angeles, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1585-4100","authenticated-orcid":false,"given":"Johannes","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"10Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-4028","authenticated-orcid":false,"given":"Maria Elisa","family":"Mancuso","sequence":"additional","affiliation":[{"name":"11IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy"},{"name":"12Humanitas University, Pieve Emanuele, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaan","family":"Kavakli","sequence":"additional","affiliation":[{"name":"13Ege University Children\u2019s Hospital Department of Hematology, Bornova, \u0130zmir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3273-9649","authenticated-orcid":false,"given":"Anna","family":"Kiialainen","sequence":"additional","affiliation":[{"name":"3F. Hoffmann-La Roche Ltd, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Deb","sequence":"additional","affiliation":[{"name":"14Genentech, Inc, South San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Niggli","sequence":"additional","affiliation":[{"name":"3F. Hoffmann-La Roche Ltd, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Chang","sequence":"additional","affiliation":[{"name":"15Spark Therapeutics, Inc, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Lehle","sequence":"additional","affiliation":[{"name":"3F. Hoffmann-La Roche Ltd, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0904-4360","authenticated-orcid":false,"given":"Karin","family":"Fijnvandraat","sequence":"additional","affiliation":[{"name":"16University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"suppl 6","key":"2024041714101228300_bib1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/hae.14046","article-title":"WFH guidelines for the management of hemophilia, 3rd edition","volume":"26","author":"Srivastava","year":"2020","journal-title":"Haemophilia"},{"issue":"4","key":"2024041714101228300_bib2","first-page":"1368","article-title":"Mild and moderate hemophilia A: neglected conditions, still with unmet needs","volume":"12","author":"Castaman","year":"2023","journal-title":"J\u00a0Clin Med"},{"issue":"11","key":"2024041714101228300_bib3","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1111\/jth.12672","article-title":"Definitions in hemophilia: communication from the SSC of the ISTH","volume":"12","author":"Blanchette","year":"2014","journal-title":"J\u00a0Thromb Haemost"},{"issue":"11","key":"2024041714101228300_bib4","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1182\/bloodadvances.2019001311","article-title":"Young adult outcomes of childhood prophylaxis for severe hemophilia A: results of the joint Outcome Continuation Study","volume":"4","author":"Warren","year":"2020","journal-title":"Blood Adv"},{"issue":"26","key":"2024041714101228300_bib5","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1182\/blood.2021011849","article-title":"Incidence and mortality rates of intracranial hemorrhage in hemophilia: a systematic review and meta-analysis","volume":"138","author":"Zwagemaker","year":"2021","journal-title":"Blood"},{"key":"2024041714101228300_bib6","doi-asserted-by":"crossref","first-page":"20406207231165857","DOI":"10.1177\/20406207231165857","article-title":"Considerations for shared decision management in previously untreated patients with hemophilia A or B","volume":"14","author":"Astermark","year":"2023","journal-title":"Ther Adv Hematol"},{"issue":"26","key":"2024041714101228300_bib7","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1056\/NEJM199012273232604","article-title":"Human recombinant DNA\u2013derived antihemophilic factor (factor VIII) in the treatment of hemophilia A","volume":"323","author":"Schwartz","year":"1990","journal-title":"N\u00a0Engl J Med"},{"issue":"3","key":"2024041714101228300_bib8","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1111\/hae.13754","article-title":"From the voices of people with haemophilia A and their caregivers: challenges with current treatment, their impact on quality of life and desired improvements in future therapies","volume":"25","author":"Wiley","year":"2019","journal-title":"Haemophilia"},{"issue":"2","key":"2024041714101228300_bib9","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1046\/j.1365-2516.2003.00840.x","article-title":"Central venous access devices in haemophilia","volume":"10","author":"Valentino","year":"2004","journal-title":"Haemophilia"},{"issue":"2","key":"2024041714101228300_bib10","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/hae.14729","article-title":"Primary prophylaxis in children with severe haemophilia A and B\u2013implementation over the last 20 years as illustrated in real-world data in the PedNet cohorts","volume":"29","author":"Ljung","year":"2023","journal-title":"Haemophilia"},{"issue":"3","key":"2024041714101228300_bib11","first-page":"249","article-title":"Diagnostic and therapeutic challenges of intracranial hemorrhage in neonates with congenital hemophilia: a case report and review","volume":"12","author":"Singleton","year":"2012","journal-title":"Ochsner J"},{"issue":"20","key":"2024041714101228300_bib12","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1182\/blood-2012-09-457036","article-title":"Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study","volume":"121","author":"Gouw","year":"2013","journal-title":"Blood"},{"issue":"4","key":"2024041714101228300_bib13","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1046\/j.1365-2516.2003.00780.x","article-title":"The epidemiology of inhibitors in haemophilia A: a systematic review","volume":"9","author":"Wight","year":"2003","journal-title":"Haemophilia"},{"issue":"1","key":"2024041714101228300_bib14","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s13023-018-0929-9","article-title":"Inhibitor clinical burden of disease: a comparative analysis of the CHESS data","volume":"13","author":"Oladapo","year":"2018","journal-title":"Orphanet J Rare Dis"},{"issue":"5","key":"2024041714101228300_bib15","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/ajh.23957","article-title":"Impact of inhibitors on hemophilia A mortality in the United States","volume":"90","author":"Walsh","year":"2015","journal-title":"Am J Hematol"},{"key":"2024041714101228300_bib16","unstructured":"Emicizumab. Prescribing information. Genetech, Inc. 2023. Accessed 25 November 2023. https:\/\/www.gene.com\/download\/pdf\/hemlibra_prescribing.pdf."},{"key":"2024041714101228300_bib17","unstructured":"European Medicines Agency\n          . Summary of Product Characteristics. Updated September 2022. Accessed 25 November 2023. https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/hemlibra-epar-product-information_en.pdf."},{"issue":"9","key":"2024041714101228300_bib18","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1056\/NEJMoa1703068","article-title":"Emicizumab prophylaxis in hemophilia A with\u00a0inhibitors","volume":"377","author":"Oldenburg","year":"2017","journal-title":"N\u00a0Engl J Med"},{"issue":"24","key":"2024041714101228300_bib19","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1182\/blood.2019001869","article-title":"A\u00a0multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors","volume":"134","author":"Young","year":"2019","journal-title":"Blood"},{"issue":"9","key":"2024041714101228300_bib20","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1056\/NEJMoa1803550","article-title":"Emicizumab prophylaxis in patients with hemophilia A without inhibitors","volume":"379","author":"Mahlangu","year":"2018","journal-title":"N\u00a0Engl J Med"},{"issue":"6","key":"2024041714101228300_bib21","doi-asserted-by":"crossref","first-page":"E295","DOI":"10.1016\/S2352-3026(19)30054-7","article-title":"Efficacy, safety, and pharmacokinetics of emicizumab prophylaxis given every 4 weeks in people with haemophilia A (HAVEN 4): a multicentre, open-label, non-randomised phase 3 study","volume":"6","author":"Pipe","year":"2019","journal-title":"Lancet Haematol"},{"issue":"2","key":"2024041714101228300_bib22","doi-asserted-by":"crossref","first-page":"e12670","DOI":"10.1002\/rth2.12670","article-title":"Prophylactic emicizumab for hemophilia A in the Asia-Pacific region: a randomized study (HAVEN 5)","volume":"6","author":"Yang","year":"2022","journal-title":"Res Pract Thromb Haemost"},{"issue":"3","key":"2024041714101228300_bib23","doi-asserted-by":"crossref","first-page":"e168","DOI":"10.1016\/S2352-3026(22)00377-5","article-title":"Emicizumab in people with moderate or mild haemophilia A (HAVEN 6): a multicentre, open-label, single-arm, phase 3 study","volume":"10","author":"N\u00e9grier","year":"2023","journal-title":"Lancet Haematol"},{"issue":"12","key":"2024041714101228300_bib24","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1007\/s40262-020-00904-z","article-title":"Population pharmacokinetic analysis\u00a0and exploratory exposure-bleeding rate relationship of emicizumab in adult and\u00a0pediatric persons with hemophilia A","volume":"59","author":"Retout","year":"2020","journal-title":"Clin\u00a0Pharmacokinet"},{"issue":"6","key":"2024041714101228300_bib25","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1111\/hae.13848","article-title":"A\u00a0multicentre, open-label study of emicizumab given every 2 or 4 weeks in children with severe haemophilia A without inhibitors","volume":"25","author":"Shima","year":"2019","journal-title":"Haemophilia"},{"issue":"11","key":"2024041714101228300_bib26","doi-asserted-by":"crossref","first-page":"e27886","DOI":"10.1002\/pbc.27886","article-title":"Emicizumab prophylaxis among infants and toddlers with severe hemophilia A and inhibitors-a single-center cohort","volume":"66","author":"Barg","year":"2019","journal-title":"Pediatr Blood Cancer"},{"issue":"5","key":"2024041714101228300_bib27","doi-asserted-by":"crossref","first-page":"e28942","DOI":"10.1002\/pbc.28942","article-title":"Real-world case series and summary of current literature of infants and toddlers with severe hemophilia A with inhibitor on prophylaxis with emicizumab","volume":"68","author":"Garcia","year":"2021","journal-title":"Pediatr Blood Cancer"},{"issue":"5","key":"2024041714101228300_bib28","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1111\/hae.14353","article-title":"Emicizumab prophylaxis in infants with severe haemophilia A without inhibitors: illustrative real-world cases to support shared decision-making","volume":"27","author":"Mason","year":"2021","journal-title":"Haemophilia"},{"key":"2024041714101228300_bib29","unstructured":"Retout\n              S\n            , GrimmH, PetryC, SchmittC, . A\u00a0model-based extrapolation enabled labelling of emicizumab in haemophilia A paediatric patients &lt;1 year old despite lack of clinical data. Population Approach Group Europe; 2019. Accessed 25 November 2023. https:\/\/www.page-meeting.org\/?abstract=9089."},{"issue":"2","key":"2024041714101228300_bib30","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1002\/jcph.1968","article-title":"A\u00a0model-based framework to inform the dose selection and study design of emicizumab for pediatric patients with hemophilia A","volume":"62","author":"Yoneyama","year":"2022","journal-title":"J\u00a0Clin Pharmacol"},{"key":"2024041714101228300_bib31","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1002\/rth2.12212","article-title":"Developing a new scoring scheme for the Hemophilia Joint Health Score 2.1","volume":"3","author":"Ribeiro","year":"2019","journal-title":"Res Pract Thromb Haemost"},{"issue":"6","key":"2024041714101228300_bib32","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1111\/j.1365-2516.2012.02883.x","article-title":"An MRI scale for assessment of haemophilic arthropathy from the International Prophylaxis Study Group","volume":"18","author":"Lundin","year":"2012","journal-title":"Haemophilia"},{"issue":"3","key":"2024041714101228300_bib33","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1055\/s-0040-1717114","article-title":"Pharmacokinetics and pharmacodynamics of emicizumab in persons with hemophilia A\u00a0with factor VIII inhibitors: HAVEN 1 study","volume":"121","author":"Schmitt","year":"2021","journal-title":"Thromb Haemost"},{"issue":"6","key":"2024041714101228300_bib34","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1111\/hae.14398","article-title":"Low immunogenicity of emicizumab in persons with haemophilia A","volume":"27","author":"Schmitt","year":"2021","journal-title":"Haemophilia"},{"issue":"2","key":"2024041714101228300_bib35","doi-asserted-by":"crossref","first-page":"e84","DOI":"10.1111\/ijlh.13384","article-title":"Validation of the chromogenic Bethesda assay for factor VIII inhibitors in hemophilia a patients receiving Emicizumab","volume":"43","author":"Miller","year":"2021","journal-title":"Int J Lab Hematol"},{"issue":"16","key":"2024041714101228300_bib36","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1182\/blood.2020009217","article-title":"Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1\u20134 studies","volume":"137","author":"Callaghan","year":"2021","journal-title":"Blood"},{"key":"2024041714101228300_bib37","unstructured":"National Hemophilia Association\n          . MASAC recommendation on the use and management of emicizumab-kxwh (Hemlibra\u00ae) for hemophilia A with and without inhibitors. MASAC Document #258. Accessed 25 November 2023. https:\/\/www.hemophilia.org\/sites\/default\/files\/document\/files\/258_emicizumab.pdf."},{"issue":"suppl 1","key":"2024041714101228300_bib38","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1182\/blood-2022-157264","article-title":"Emicizumab prophylaxis for the treatment of infants with severe hemophilia A without factor VIII inhibitors: results from the interim analysis of the HAVEN 7 study","volume":"140","author":"Pipe","year":"2022","journal-title":"Blood"},{"issue":"6","key":"2024041714101228300_bib39","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1002\/cpdd.617","article-title":"Relative and absolute bioavailability study of emicizumab to bridge drug products and subcutaneous injection sites in healthy volunteers","volume":"8","author":"Kotani","year":"2019","journal-title":"Clin Pharmacol Drug Dev"},{"issue":"1","key":"2024041714101228300_bib40","doi-asserted-by":"crossref","first-page":"102306","DOI":"10.1016\/j.rpth.2023.102306","article-title":"Pharmacokinetics and coagulation biomarkers in children and adults with hemophilia A receiving emicizumab prophylaxis every one, two, or four weeks","volume":"8","author":"Kiialainen","year":"2024","journal-title":"Res Pract Thromb Haemost"},{"issue":"1","key":"2024041714101228300_bib41","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1182\/blood.V70.1.165.165","article-title":"Development of the human coagulation system in the full-term infant","volume":"70","author":"Andrew","year":"1987","journal-title":"Blood"},{"issue":"2","key":"2024041714101228300_bib42","doi-asserted-by":"crossref","first-page":"e136","DOI":"10.1111\/hae.12364","article-title":"Severe and moderate haemophilia A and B in US females","volume":"20","author":"Di Michele","year":"2014","journal-title":"Haemophilia"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/143\/14\/1355\/2222424\/blood_bld-2023-021832-main.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/blood\/article-pdf\/143\/14\/1355\/2222424\/blood_bld-2023-021832-main.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T14:10:49Z","timestamp":1713363049000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/143\/14\/1355\/506683\/Emicizumab-prophylaxis-in-infants-with-hemophilia"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,4]]},"references-count":42,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2024,4,4]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2023021832","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,4]]}}}