PMID- 37309365
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230614
IS  - 1179-2736 (Print)
IS  - 1179-2736 (Electronic)
IS  - 1179-2736 (Linking)
VI  - 14
DP  - 2023
TI  - Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) 
      Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical Trials.
PG  - 379-388
LID - 10.2147/JBM.S405624 [doi]
AB  - INTRODUCTION: Previous clinical trials established the efficacy and safety of 
      sucrose-formulated recombinant factor (F) VIII (rFVIII-FS/Kogenate FS(R)/Helixate 
      FS(R)) and octocog alfa (BAY 81-8973/Kovaltry(R); LEOPOLD trials). AIM: To report the 
      results of a post hoc subgroup analysis assessing efficacy and safety outcomes in 
      patients with hemophilia A who were receiving rFVIII-FS prior to enrolling into 
      the LEOPOLD I Part B and LEOPOLD Kids Part A clinical trials and switching to 
      octocog alfa. METHODS: LEOPOLD I Part B (NCT01029340) and LEOPOLD Kids Part A 
      (NCT01311648) were octocog alfa Phase 3, multinational, open-label studies in 
      patients with severe hemophilia A aged 12-65 years and </=12 years, respectively. 
      Annualized bleeding rate (ABR) was the efficacy endpoint for both studies. Safety 
      endpoints included adverse events (AEs) and development of FVIII inhibitors. 
      RESULTS: Of the 113 patients in both LEOPOLD trials, 40 (35.4%) patients received 
      rFVIII-FS prophylaxis pre-study and had data available for pre-study total ABR. 
      In LEOPOLD I Part B (n = 22, 35.5%), median (Q1; Q3) total ABR decreased from 2.5 
      (0.0; 9.0) pre-study to 1.0 (0.0; 6.8), and from 1.0 (0.0; 6.0) pre-study to 0.0 
      (0.0; 6.02) in LEOPOLD Kids Part A (n = 18, 35.3%). Octocog alfa was well 
      tolerated, and no patients had drug-related serious AEs or inhibitors. 
      CONCLUSION: Treatment with octocog alfa prophylaxis appeared to have a favorable 
      risk-benefit profile compared with rFVIII-FS and thus could be an effective and 
      improved alternative strategy for individualized treatment for children, 
      adolescent and adult patients with severe hemophilia A currently on rFVIII-FS 
      treatment.
CI  - (c) 2023 Kenet et al.
FAU - Kenet, Gili
AU  - Kenet G
AD  - National Hemophilia Center, Sheba Medical Center, Tel HaShomer, Israel.
AD  - The Amalia Biron Thrombosis Research Institute, Tel Aviv University, Tel Aviv, 
      Israel.
FAU - Moulton, Thomas
AU  - Moulton T
AD  - Bayer, Whippany, NJ, USA.
FAU - Wicklund, Brian M
AU  - Wicklund BM
AUID- ORCID: 0000-0002-5903-9001
AD  - Children's Mercy-Kansas City, Kansas City, MO, USA.
FAU - Ahuja, Sanjay P
AU  - Ahuja SP
AD  - Rainbow Babies & Children's Hospital, Cleveland, OH, USA.
FAU - Escobar, Miguel
AU  - Escobar M
AUID- ORCID: 0000-0002-2944-0240
AD  - University of Texas Health Science Center, Houston, TX, USA.
FAU - Mahlangu, Johnny
AU  - Mahlangu J
AUID- ORCID: 0000-0001-5781-7669
AD  - Hemophilia Comprehensive Care Center, Faculty of Health Sciences, Charlotte 
      Maxeke Johannesburg Academic Hospital, University of the Witwatersrand, and 
      National Health Laboratory Service, Johannesburg, South Africa.
LA  - eng
PT  - Journal Article
DEP - 20230607
PL  - New Zealand
TA  - J Blood Med
JT  - Journal of blood medicine
JID - 101550884
PMC - PMC10257928
OTO - NOTNLM
OT  - FVIII
OT  - hemophilia A
OT  - octocog alfa
OT  - prophylaxis
OT  - recombinant proteins
COIS- G. Kenet: is a member of the Board of Directors/advisory committees and has 
      received consultancy fees from ASC therapeutics, Roche, Sobi, Uniquore, Bayer, 
      Pfizer, BioMarin, Takeda, Roche, Novo Nordisk, Sanofi, PI Healthcare and CSL 
      Behring; has received research funding from BSF, Opko Biologics, Bayer, Pfizer, 
      Roche, Alnylam (Sanofi) and Shire; has received honoraria for participation in 
      speakers' bureaus from Bayer, BPL, CSL, Roche, Sanofi-Genzyme, Sobi, Spark, 
      Uniquore, Pfizer, Takeda, BioMarin and Novo Nordisk. T. Moulton: is a Bayer 
      employee. B. M. Wicklund: has received consultancy fees from Bayer, Genentech, 
      Novo Nordisk and Shire. S. P. Ahuja: has received consultancy fees from 
      Genentech, Sanofi Genzyme, CSL Behring and XaTek, Inc.; has received patent 
      royalties and research funding from XaTek, Inc. He also has a patent with 
      royalties for ClotChip and a patent for TraumaChek issued to US Patent office. M. 
      Escobar is a member of the advisory boards and/or has received consultancy fees 
      from Biomarin, Novo Nordisk, CSL Behring, Genentech/Roche, Sanofi, Takeda, 
      Pfizer, Bayer, Kedrion, Hemobiologics/LFB, National Hemophilia Foundation, 
      UniQure. J. Mahlangu is a member of the scientific advisory committee of Amgen, 
      Bayer, Baxalta, Biogen, Biotest, CSL Behring, Catalyst Biosciences, Novo Nordisk, 
      Roche and Spark; has received research grants from Bayer, Biogen, BioMarin, CSL 
      Behring, Novartis, Sanofi, Spark, Takeda, Novo Nordisk, Sobi, Roche, Uniqure; has 
      received honoraria for participation in speakers' bureaus from Alnylam, Bayer, 
      Biogen, Biotest, ISTH, Novo Nordisk, Pfizer, Roche, Sobi, Shire, and World 
      Federation of Hemophilia. The authors report no other conflicts of interest in 
      this work.
EDAT- 2023/06/13 06:42
MHDA- 2023/06/13 06:43
PMCR- 2023/06/07
CRDT- 2023/06/13 03:50
PHST- 2023/01/21 00:00 [received]
PHST- 2023/05/18 00:00 [accepted]
PHST- 2023/06/13 06:43 [medline]
PHST- 2023/06/13 06:42 [pubmed]
PHST- 2023/06/13 03:50 [entrez]
PHST- 2023/06/07 00:00 [pmc-release]
AID - 405624 [pii]
AID - 10.2147/JBM.S405624 [doi]
PST - epublish
SO  - J Blood Med. 2023 Jun 7;14:379-388. doi: 10.2147/JBM.S405624. eCollection 2023.