PMID- 34430790
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240403
IS  - 2475-0379 (Electronic)
IS  - 2475-0379 (Linking)
VI  - 5
IP  - 6
DP  - 2021 Aug
TI  - Subcutaneous engineered factor VIIa marzeptacog alfa (activated) in hemophilia 
      with inhibitors: Phase 2 trial of pharmacokinetics, pharmacodynamics, efficacy, 
      and safety.
PG  - e12576
LID - 10.1002/rth2.12576 [doi]
LID - e12576
AB  - BACKGROUND: Marzeptacog alfa (activated) (MarzAA), a novel recombinant activated 
      human factor VII (FVIIa) variant, was developed to provide increased procoagulant 
      activity, subcutaneous (SC) administration, and longer duration of action in 
      people with hemophilia. OBJECTIVES: To investigate if daily SC administration of 
      MarzAA in subjects with inhibitors can provide effective prophylaxis. METHODS: 
      This multicenter, open-label phase 2 trial (NCT03407651) enrolled men with severe 
      congenital hemophilia with an inhibitor. All subjects had a baseline annualized 
      bleeding rate (ABR) of >/=12 events/year. Subjects received a single 18 mug/kg 
      intravenous dose of MarzAA to measure 24-hour pharmacokinetics (PK) and 
      pharmacodynamics (PD), single 30 mug/kg SC dose to measure 48-hour PK/PD, then 
      daily SC 30 mug/kg MarzAA for 50 days. If spontaneous bleeding occurred, the dose 
      was sequentially escalated to 60, 90, or 120 mug/kg, with 50 days at the final 
      effective dose without spontaneous bleeding to proceed to a 30-day follow-up. The 
      primary end point was reduction in ABR. Secondary end points were safety, 
      tolerability, and antidrug antibody (ADA) formation. RESULTS: In the 11 subjects, 
      the mean ABR significantly reduced from 19.8 to 1.6, and the mean proportion of 
      days with bleeding significantly reduced from 12.3% to 0.8%. Of a total of 517 SC 
      doses, six injection site reactions in two subjects were reported. No ADAs were 
      detected. One fatal unrelated serious adverse event occurred: intracerebral 
      hemorrhage due to untreated hypertension. CONCLUSIONS: The data demonstrated that 
      MarzAA was highly efficacious for prophylactic treatment in patients with 
      inhibitors by significantly decreasing bleed frequency and duration of bleeding 
      episodes.
CI  - (c) 2021 Catalyst Biosciences. Research and Practice in Thrombosis and Haemostasis 
      published by Wiley Periodicals LLC on behalf of International Society on 
      Thrombosis and Haemostasis (ISTH).
FAU - Mahlangu, Johnny
AU  - Mahlangu J
AD  - Haemophilia Comprehensive Care Center Charlotte Maxeke Johannesburg Academic 
      Hospital University of the Witwatersrand and NHLS Johannesburg South Africa.
FAU - Levy, Howard
AU  - Levy H
AD  - Catalyst Biosciences South San Francisco CA USA.
FAU - Kosinova, Marina V
AU  - Kosinova MV
AD  - Hematology Kemerovo Regional Clinical Hospital Kemerovo Russia.
FAU - Khachatryan, Heghine
AU  - Khachatryan H
AD  - R.H. Yeolyan Hemophilia and Thrombophilia Center Yerevan Republic of Armenia.
FAU - Korczowski, Bartosz
AU  - Korczowski B
AD  - Institute of Medical Sciences College of Medical Sciences of the University of 
      Rzeszow, University of Rzeszow Rzeszow Poland.
FAU - Makhaldiani, Levani
AU  - Makhaldiani L
AD  - K. Eristavi National Center of Experimental and Clinical Surgery Tbilisi Georgia.
FAU - Iosava, Genadi
AU  - Iosava G
AD  - Institute of Hematology and Transfusiology Tbilisi Georgia.
FAU - Lee, Martin
AU  - Lee M
AD  - Fielding School of Public Health University of California Los Angeles Los Angeles 
      CA USA.
FAU - Del Greco, Frank
AU  - Del Greco F
AD  - Catalyst Biosciences South San Francisco CA USA.
LA  - eng
PT  - Journal Article
DEP - 20210817
PL  - United States
TA  - Res Pract Thromb Haemost
JT  - Research and practice in thrombosis and haemostasis
JID - 101703775
PMC - PMC8371347
OTO - NOTNLM
OT  - *hemophilia
OT  - *marzeptacog alfa (activated)
OT  - *prophylaxis
OT  - *recombinant FVIIa
OT  - *subcutaneous injection
EDAT- 2021/08/26 06:00
MHDA- 2021/08/26 06:01
PMCR- 2021/08/17
CRDT- 2021/08/25 06:30
PHST- 2021/06/22 00:00 [received]
PHST- 2021/07/15 00:00 [revised]
PHST- 2021/07/27 00:00 [accepted]
PHST- 2021/08/25 06:30 [entrez]
PHST- 2021/08/26 06:00 [pubmed]
PHST- 2021/08/26 06:01 [medline]
PHST- 2021/08/17 00:00 [pmc-release]
AID - S2475-0379(22)01441-8 [pii]
AID - RTH212576 [pii]
AID - 10.1002/rth2.12576 [doi]
PST - epublish
SO  - Res Pract Thromb Haemost. 2021 Aug 17;5(6):e12576. doi: 10.1002/rth2.12576. 
      eCollection 2021 Aug.