Simoctocog Alfa (Nuwiq) in Previously Untreated Patients with Severe Haemophilia A: Final Results of the NuProtect Study.

Abstract

INTRODUCTION:

 FVIII inhibitor development is the most serious contemporary treatment complication in haemophilia A, particularly in previously untreated patients (PUPs). No inhibitors developed in clinical trials in previously treated patients treated with simoctocog alfa (Nuwiq), a fourth-generation recombinant FVIII produced in a human cell line.

METHODS:

 The NuProtect study investigated the immunogenicity of simoctocog alfa in PUPs. NuProtect was a prospective, multinational, open-label, non-controlled, phase III study. PUPs with severe haemophilia A (FVIII:C <1%) of any age and ethnicity were treated with simoctocog alfa for 100 exposure days or a maximum of 5 years. Patients were true PUPs without prior exposure to FVIII concentrates or blood components. Inhibitor titres were measured with the Nijmegen-modified Bethesda assay; cut-off for positivity was 0.6 BU mL-1 (≥0.6 to <5 low-titre, ≥5 high titre).

RESULTS:

 A total of 108 PUPs with a median age at first treatment of 12.0 months (interquartile range: 8.0-23.5) were treated with simoctocog alfa. F8 mutation type was known for 102 patients (94.4%) of whom 90 (88.2%) had null F8 mutations and 12 (11.8%) had non-null mutations. Of 105 PUPs evaluable for inhibitor development, 28 (26.7%) developed inhibitors; 17 high titre (16.2%) and 11 low titre (10.5%). No PUPs with non-null F8 mutations developed inhibitors.

CONCLUSION:

 In the NuProtect study, the rate of inhibitor development in PUPs with severe haemophilia A treated with simoctocog alfa was lower than the rate reported for hamster-cell-derived recombinant factor VIII products in other recent clinical trials. No inhibitors were reported in PUPs with non-null F8 mutations.

• Authors: Ri J Liesner, Aby Abraham, Carmen Altisent, Mark J Belletrutti, Manuel Carcao, Manuela Carvalho, Hervé Chambost, Anthony K C Chan, Leonid Dubey, Jonathan Ducore, Michael Gattens, Paolo Gresele, Yves Gruel, Benoit Guillet, Victor Jimenez-Yuste, Lidija Kitanovski, Anna Klukowska, Sunil Lohade, Maria Elisa Mancuso, Johannes Oldenburg, Anna Pavlova, Berardino Pollio, Marianne Sigaud, Vladimir Vdovin, Kateryna Vilchevska, John K M Wu, Martina Jansen, Larisa Belyanskaya, Olaf Walter, Sigurd Knaub, Ellis J Neufeld
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 121 Issue 11 Pg. 1400-1408 (Nov 2021) ISSN: 2567-689X [Electronic] Germany
• PMID: 33581698 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study)
• Copyright: The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).

Chemical References

• Antibodies
• Coagulants
• Recombinant Proteins
• F8 protein, human
• Factor VIII

Topics

• Antibodies (blood)
• Coagulants (immunology, therapeutic use)
• Factor VIII (genetics, immunology, therapeutic use)
• Genetic Predisposition to Disease
• Hemophilia A (blood, drug therapy, genetics)
• Hemorrhage (blood, diagnosis, genetics, prevention & control)
• Humans
• Infant
• Male
• Mutation
• Prospective Studies
• Recombinant Proteins (immunology, therapeutic use)
• Severity of Illness Index
• Time Factors
• Treatment Outcome