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The authors thank the patients, their families, and all trial investigators for their participation and support in explorer4 and explorer5, and also the external independent data monitoring committee for their assistance with these studies. These studies were funded by Novo Nordisk A/S. Medical writing support, under the direction of the authors, was provided by Ashfield MedComms GmbH (an Ashfield Health company) and was funded by Novo Nordisk A/S.

Analysis of institutional authors

Jimenez-Yuste, VAuthor

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Article

Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors

Publicated to:Blood Advances. 6 (11): 3422-3432 - 2022-06-09 6(11), DOI: 10.1182/bloodadvances.2021006403

Authors: Shapiro, Amy D; Angchaisuksiri, Pantep; Astermark, Jan; Benson, Gary; Castaman, Giancarlo; Eichler, Hermann; Jimenez-Yuste, Victor; Kavakli, Kaan; Matsushita, Tadashi; Poulsen, Lone Hvitfeldt; Wheeler, Allison P; Young, Guy; Zupancic-Salek, Silva; Oldenburg, Johannes; Chowdary, Pratima

Affiliations

Aarhus Univ, Hemophilia Ctr, Dept Haematol, Aarhus, Denmark - Author
Belfast Hlth & Social Care Trust, Dept Hematol, Belfast, North Ireland - Author
Careggi Univ Hosp, Ctr Bleeding Disorders & Coagulat, Dept Oncol, Florence, Italy - Author
Ege Univ, Dept Hematol, Childrens Hosp, Izmir, Turkey - Author
Indiana Hemophilia & Thrombosis Ctr, 8326 Naab Rd, Indianapolis, IN 46260 USA - Author
Indiana Hemophilia & Thrombosis Ctr, Indianapolis, IN USA - Author
La Paz Univ Hosp, Univ Autonoma Madrid, Haematol Dept, Madrid, Spain - Author
Lund Univ, Skane Univ Hosp, Ctr Thrombosis & Haemostasis, Malmo, Sweden - Author
Mahidol Univ, Ramathibodi Hosp, Dept Med, Div Hematol, Bangkok, Thailand - Author
Nagoya Univ Hosp, Dept Transfus Med, Nagoya, Japan - Author
Royal Free London NHS Fdn Trust, Hemophilia Ctr, London, England - Author
Saarland Univ, Inst Clin Hemostaseol & Transfus Med, Homburg, Germany - Author
Univ Clin, Inst Expt Hematol & Transfus Med, Dept Immunohematol, Bonn, Germany - Author
Univ Clin, Inst Expt Hematol & Transfus Med, Dept Mol Hemostasis, Bonn, Germany - Author
Univ Hosp Ctr Zagreb, Dept Haematol, Zagreb, Croatia - Author
Univ Osijek, Sch Med, Osijek, Croatia - Author
Univ Southern Calif, Childrens Hosp Angeles, Hemostasis & Thrombosis Ctr, Keck Sch Med, Los Angeles, CA USA - Author
Univ Zagreb, Sch Med, Zagreb, Croatia - Author
Vanderbilt Univ Sch Med, Dept Pathol, Microbiol & Immunol, Nashville, TN USA - Author
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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 + 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 + 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. These trials were registered at www.clinicaltrials.gov as #NCT03196284 and #NCT03196297.

Keywords

Antibodies, monoclonal, humanizedClinical trials as topicConcizumabEmicizumabHemophilia aHemophilia bHemorrhageHumansManagement

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Blood Advances due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 13/79, thus managing to position itself as a Q1 (Primer Cuartil), in the category Hematology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 5.88. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 7.09 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 20.78 (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-14, the following number of citations:

  • WoS: 26
  • Scopus: 39
  • OpenCitations: 28

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-14:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 63.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 63 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 2.6.
  • The number of mentions on the social network Facebook: 1 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 4 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://repositorio.uam.es/handle/10486/707460

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Croatia; Denmark; Germany; India; Italy; Japan; Sweden; Thailand; Turkey; United Kingdom; United States of America.