PMID- 38127586
OWN - NLM
STAT- MEDLINE
DCOM- 20240405
LR  - 20240426
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 143
IP  - 14
DP  - 2024 Apr 4
TI  - Emicizumab prophylaxis in infants with hemophilia A (HAVEN 7): primary analysis 
      of a phase 3b open-label trial.
PG  - 1355-1364
LID - 10.1182/blood.2023021832 [doi]
AB  - 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 </=12 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, 0.30-0.63), with 54.5% of participants (n = 30) having zero treated 
      bleeds. No ICH occurred. All 42 treated bleeds in 25 participants (45.5%) were 
      traumatic. Nine participants (16.4%) had >/=1 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.
CI  - (c) 2024 American Society of Hematology. Published by Elsevier Inc. All rights are 
      reserved, including those for text and data mining, AI training, and similar 
      technologies.
FAU - Pipe, Steven W
AU  - Pipe SW
AUID- ORCID: 0000-0003-2558-2089
AD  - University of Michigan, Ann Arbor, MI.
FAU - Collins, Peter
AU  - Collins P
AD  - School of Medicine, Cardiff University, Cardiff, United Kingdom.
FAU - Dhalluin, Christophe
AU  - Dhalluin C
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Kenet, Gili
AU  - Kenet G
AD  - Sheba Medical Center, Ramat Gan, Israel.
AD  - Tel Aviv University, Tel Aviv, Israel.
FAU - Schmitt, Christophe
AU  - Schmitt C
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Buri, Muriel
AU  - Buri M
AUID- ORCID: 0000-0001-7432-4874
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Jimenez-Yuste, Victor
AU  - Jimenez-Yuste V
AUID- ORCID: 0000-0003-3937-3499
AD  - La Paz University Hospital-IdiPaz, Autonoma University, Madrid, Spain.
FAU - Peyvandi, Flora
AU  - Peyvandi F
AUID- ORCID: 0000-0001-7423-9864
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi 
      Hemophilia and Thrombosis Center, Milan, Italy.
AD  - Universita degli Studi di Milano, Milan, Italy.
FAU - Young, Guy
AU  - Young G
AUID- ORCID: 0000-0001-6013-1254
AD  - Children's Hospital Los Angeles, Los Angeles, CA.
FAU - Oldenburg, Johannes
AU  - Oldenburg J
AUID- ORCID: 0000-0002-1585-4100
AD  - Institute of Experimental Hematology and Transfusion Medicine, University 
      Hospital Bonn, Medical Faculty, University of Bonn, Bonn, Germany.
FAU - Mancuso, Maria Elisa
AU  - Mancuso ME
AUID- ORCID: 0000-0002-7113-4028
AD  - IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
AD  - Humanitas University, Pieve Emanuele, Milan, Italy.
FAU - Kavakli, Kaan
AU  - Kavakli K
AD  - Ege University Children's Hospital Department of Hematology, Bornova, Izmir, 
      Turkey.
FAU - Kiialainen, Anna
AU  - Kiialainen A
AUID- ORCID: 0000-0002-3273-9649
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Deb, Sonia
AU  - Deb S
AD  - Genentech, Inc, South San Francisco, CA.
FAU - Niggli, Markus
AU  - Niggli M
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Chang, Tiffany
AU  - Chang T
AD  - Spark Therapeutics, Inc, San Francisco, CA.
FAU - Lehle, Michaela
AU  - Lehle M
AD  - F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Fijnvandraat, Karin
AU  - Fijnvandraat K
AUID- ORCID: 0000-0003-0904-4360
AD  - University of Amsterdam, Amsterdam, The Netherlands.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 9001-27-8 (Factor VIII)
RN  - 7NL2E3F6K3 (emicizumab)
RN  - 0 (Antibodies, Bispecific)
RN  - 0 (Antibodies, Monoclonal, Humanized)
SB  - IM
CIN - Blood. 2024 Apr 4;143(14):1317-1318. PMID: 38573607
MH  - Infant
MH  - Humans
MH  - Male
MH  - Infant, Newborn
MH  - *Hemophilia A
MH  - Factor VIII
MH  - Hemorrhage/chemically induced/prevention & control/drug therapy
MH  - *Antibodies, Bispecific/adverse effects
MH  - *Thrombotic Microangiopathies/drug therapy
MH  - Intracranial Hemorrhages
MH  - *Antibodies, Monoclonal, Humanized
PMC - PMC11033591
COIS- Conflict-of-interest disclosure: S.W.P. is a member of the scientific advisory 
      board for GeneVentiv and Equilibra Bioscience and has received grants or 
      contracts from Siemens; consulting fees from Apcintex, ASC Therapeutics, Bayer, 
      BioMarin, CSL Behring, HEMA Biologics, Freeline, LFB Group, Novo Nordisk, Pfizer, 
      Regeneron/Intellia, Genentech, Inc./F. Hoffmann-La Roche Ltd, Sanofi, Takeda, 
      Spark Therapeutics, and uniQure. P.C. is a member on an entity's board of 
      directors for the HAVEN 7 trial steering committee and a member of the UK 
      Haemophilia Centre Doctors' Organization, which has received a research grant 
      from F. Hoffmann-La Roche Ltd. C.D. is an employee of F. Hoffmann-La Roche Ltd. 
      G.K. has received grants/research support funding from Binational Science 
      Foundation, Pfizer, F. Hoffmann-La Roche Ltd, Tel Aviv University, and Sheba 
      research authorities; consulting fees from ASC Therapeutics, Bayer, BioMarin, 
      Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd, Sobi, Sanofi-Genzyme, Takeda, and 
      uniQure; honoraria from Bayer, BioMarin, Bio Products Laboratory, CSL Behring, 
      Pfizer, Novo Nordisk, F. Hoffmann-La Roche Ltd, Sanofi-Genzyme, and Spark 
      Therapeutics; participated on a data safety monitoring board or advisory board 
      for ASC Therapeutics, BioMarin, Pfizer, Novo Nordisk, uniQure, F. Hoffmann-La 
      Roche Ltd, Sanofi-Genzyme, Sobi, and Spark Therapeutics; and has a leadership 
      role in PedNet Research foundation. C.S. and M.B. are employees and stockholders 
      of F. Hoffmann-La Roche Ltd. V.J.-Y. has received grants or contracts from F. 
      Hoffmann-La Roche Ltd, Novo Nordisk, Sobi, Takeda, Grifols, Bayer, Pfizer, 
      Octapharma, and CSL Behring; consulting fees from F. Hoffmann-La Roche Ltd, Novo 
      Nordisk, Sanofi, Sobi, Takeda, Grifols, Bayer, Pfizer, Spark Therapeutics, 
      BioMarin, Octapharma, and CSL Behring; and honoraria from F. Hoffmann-La Roche 
      Ltd, Novo Nordisk, Sanofi, Sobi, Takeda, Grifols, Bayer, Pfizer, Spark 
      Therapeutics, BioMarin, Octapharma, and CSL Behring. F.P. has received speaker 
      fees for participating in advisory boards from Sanofi, Sobi, Takeda, F. 
      Hoffmann-La Roche Ltd, and BioMarin; and educational meeting fees from Grifols 
      and F. Hoffmann-La Roche Ltd. G.Y. has received grants or contracts from 
      Genentech, Inc., Grifols, and Takeda; royalties or licenses from Viatris; 
      consulting fees from Bayer, BioMarin, CSL Behring, Genentech, Inc./F. Hoffmann-La 
      Roche Ltd, LFB Group, Novo Nordisk, Pfizer, Sanofi, Spark Therapeutics, and 
      Takeda; honoraria from Bayer, BioMarin, CSL Behring, Genentech, Inc./F. 
      Hoffmann-La Roche Ltd, Novo Nordisk, Pfizer, Sanofi, Spark Therapeutics, and 
      Takeda; and speakers bureau fees from BioMarin, Genentech, Inc., Hema Biologics, 
      Sanofi, and Spark Therapeutics. J.O. has received research funding from Bayer, 
      Biotest, CSL Behring, Octapharma, Pfizer, Swedish Orphan Biovitrum, and Takeda; 
      consultancy, speakers bureau fees, honoraria, scientific advisory board fees, and 
      travel expenses from Bayer, Biogen Idec, BioMarin, Biotest, Chugai Pharmaceutical 
      Co., Ltd, CSL Behring, Freeline, Grifols, LFB Group, Novo Nordisk, Octapharma, 
      Pfizer, F. Hoffmann-La Roche Ltd, Sanofi, Spark Therapeutics, Swedish Orphan 
      Biovitrum, and Takeda. M.E.M. has received consulting fees from Bayer, CSL 
      Behring, Novo Nordisk, F. Hoffmann-La Roche Ltd, Octapharma, Pfizer, Sanofi, 
      Sobi, Kedrion, Grifols, BioMarin, Catalyst, uniQure, and LFB Group; honoraria 
      from Bayer, CSL Behring, Novo Nordisk, F. Hoffmann-La Roche Ltd, Octapharma, 
      Pfizer, Sobi, Kedrion, Grifols, BioMarin, and Spark Therapeutics. K.K. has 
      received consulting and honoraria fees from F. Hoffmann-La Roche Ltd, Novo 
      Nordisk, Takeda, and Pfizer; and research funding from F. Hoffmann-La Roche Ltd 
      and Pfizer. S.D. is an employee of Genentech, Inc. A.K., M.N., and M.L. are 
      employees and have stock ownership in F. Hoffmann-La Roche Ltd. T.C is an 
      employee of Spark Therapeutics, which is part of the Roche group and holds stock 
      in F. Hoffmann-La Roche Ltd. The institution of K.F. has received unrestricted 
      research grants from CSL Behring, Sobi, and Novo Nordisk; and consultancy fees 
      from F. Hoffmann-La Roche Ltd, Sanofi, Sobi, and Novo Nordisk.
EDAT- 2023/12/21 18:41
MHDA- 2024/04/05 06:44
PMCR- 2023/12/23
CRDT- 2023/12/21 12:33
PHST- 2023/12/06 00:00 [accepted]
PHST- 2023/10/10 00:00 [received]
PHST- 2024/04/05 06:44 [medline]
PHST- 2023/12/21 18:41 [pubmed]
PHST- 2023/12/21 12:33 [entrez]
PHST- 2023/12/23 00:00 [pmc-release]
AID - S0006-4971(23)14713-6 [pii]
AID - 10.1182/blood.2023021832 [doi]
PST - ppublish
SO  - Blood. 2024 Apr 4;143(14):1355-1364. doi: 10.1182/blood.2023021832.