Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors
Issued Date
2022-06-14
Resource Type
ISSN
24739529
eISSN
24739537
Scopus ID
2-s2.0-85132337451
Pubmed ID
35290453
Journal Title
Blood Advances
Volume
6
Issue
11
Start Page
3422
End Page
3432
Rights Holder(s)
SCOPUS
Bibliographic Citation
Blood Advances Vol.6 No.11 (2022) , 3422-3432
Suggested Citation
Shapiro A.D., Angchaisuksiri P., Astermark J., Benson G., Castaman G., Eichler H., Jiménez-Yuste V., Kavakli K., Matsushita T., Poulsen L.H., Wheeler A.P., Young G., Zupančić-Šalek S., Oldenburg J., Chowdary P. Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors. Blood Advances Vol.6 No.11 (2022) , 3422-3432. 3432. doi:10.1182/bloodadvances.2021006403 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85795
Title
Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors
Author's Affiliation
Ramathibodi Hospital
Royal Free London NHS Foundation Trust
KBC Zagreb
Vanderbilt University Medical Center
Universitätsklinikum Bonn
Belfast Health and Social Care Trust
Aarhus Universitet
Lunds Universitet
Hospital Universitario La Paz
Nagoya University Hospital
Universitätsklinikum des Saarlandes Medizinische Fakultät der Universität des Saarlandes
Ege Üniversitesi
Azienda Ospedaliera Careggi
Sveučilište Josipa Jurja Strossmayera u Osijeku
Keck School of Medicine of USC
University of Zagreb School of Medicine
Indiana Hemophilia and Thrombosis Center
Royal Free London NHS Foundation Trust
KBC Zagreb
Vanderbilt University Medical Center
Universitätsklinikum Bonn
Belfast Health and Social Care Trust
Aarhus Universitet
Lunds Universitet
Hospital Universitario La Paz
Nagoya University Hospital
Universitätsklinikum des Saarlandes Medizinische Fakultät der Universität des Saarlandes
Ege Üniversitesi
Azienda Ospedaliera Careggi
Sveučilište Josipa Jurja Strossmayera u Osijeku
Keck School of Medicine of USC
University of Zagreb School of Medicine
Indiana Hemophilia and Thrombosis Center
Other Contributor(s)
Abstract
Despite current therapies, there remains an unmet need for treatment for patients with hemophilia. The main parts of two phase 2 trials established clinical proof-of-concept for once-daily, subcutaneous concizumab prophylaxis in patients with hemophilia A/B with inhibitors (HAwI/HBwI; explorer4) and severe hemophilia A without inhibitors (HA; explorer5). Here, we present results from extension parts of these trials, included to evaluate longer term safety and efficacy. Both trials included main ($24 weeks) and extension (52-102 weeks) parts, with patients receiving concizumab 0.15 mg/kg with potential dose escalation to concizumab 0.20 or 0.25 mg/kg if they experienced $3 treated spontaneous bleeding episodes within 12 weeks. Endpoints included annualized bleeding rate (ABR), adverse events (AEs), and occurrence of antidrug antibodies. Thromboembolic events were AEs of special interest. Thirty-six patients with HA, 15 with HAwI, and 10 with HBwI were exposed to concizumab. Estimated ABRs during the main 1 extension parts at last dose level were 4.8 (95% confidence interval [CI], 3.2-7.2) and 6.4 (95% CI, 4.1-9.9) in explorer4 and explorer5, respectively (spontaneous ABRs were 1.8 [95% CI, 1.2-2.6] and 2.1 [95% CI, 1.3-3.3]). Most AEs were mild, with no deaths, events leading to withdrawal, or thromboembolic events. Anti-drug antibodies developed in 25% of patients and were low titer and transient, with no observed clinical effect in most cases. Results of the main 1 extension parts of these trials were consistent with results of the main parts. Ongoing phase 3 trials will further evaluate concizumab as a once-daily, subcutaneous treatment across hemophilia subtypes.