OC 40.5 - Management of breakthrough bleeding episodes in the phase 3 concizumab studies

Monday, June 24, 2024

15:45 – 16:00 ICT

Room: Plenary Hall

Presenting Author(s)

Johnny Mahlangu, MBBCh, MMed

Head of Department and Principal Haematologist
Department of Molecular Medicine and Haematology, University of the Witwatersrand, National Health Laboratory Service, and Charlotte Maxeke Johannesburg Academic Hospital
Johannesburg, Gauteng, South Africa

Co-Author(s)

Giancarlo Castaman

Medical Director Hematologist
Department of Oncology Careggi University Hospital, Florence, Italy
Florence, Toscana, Italy
AA

Aby Abraham

Professor & Head, Department of Haematology
Christian Medical College, Vellore, India
Vellore, Tamil Nadu, India
JA

Jan Astermark

Professor, Senior Consultant
Department of Translational Medicine, Lund University, Malmö, Sweden
Malmo, Skane Lan, Sweden
Huyen Tran, MBBS (Hons), MClinEpi, FRACP, FRCPA

Head of the Thrombosis & Hemostasis Unit and Director of the Hemophilia Treatment Centre
Ronald Sawyers Haemophilia Centre, The Alfred Hospital, Melbourne, Victoria, Australia
Melbourne, Victoria, Australia
CS

Chunduo Shen

Principal Statistician
Novo Nordisk A/S, Søborg, Denmark
Søborg, Hovedstaden, Denmark
JB

Julien Bovet

International Medical Director
Novo Nordisk A/S, Søborg, Denmark
Søborg, Hovedstaden, Denmark
Jameela Sathar, MD, MRCP, FRCPath

Haematologist Consultant
Ampang Hospital, Ministry of Health, Kuala Lumpur, Malaysia
Petaling Jaya, Selangor, Malaysia

Background: Concizumab is an anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody in development as a once-daily subcutaneous prophylaxis for hemophilia A/B with inhibitors (HAwI/HBwI; explorer7 [NCT04083781]) and without inhibitors (HA/HB; explorer8 [NCT04082429]). Spontaneous or traumatic breakthrough bleeding (BTB) can occur in patients with hemophilia who are treated prophylactically; guidance for the management of these events should be considered.

Aims: To investigate BTB management from the phase 3 explorer7 and explorer8 56-week data.

Methods: In the phase 3 concizumab studies, bleeding episodes were reported along with the hemostatic treatment used to manage the bleed. Guidance for managing mild/moderate BTBs was included in these studies, generally using the lowest dose of the required treatment, according to local labeling. Classification of BTB severity was the responsibility of the investigator.

Results: At the 56-week cut-off, BTBs that occurred in patients receiving concizumab were most frequently in joints, occurred spontaneously, and were reported as mild/moderate in severity (Table 1). Most BTBs of mild/moderate severity were treated with one injection of the respective BTB treatment (Table 2). In people with HAwI/HBwI, bleeds were most often managed with recombinant activated factor VII (median consumption per injection: mild/moderate bleeds in HAwI 90.0 µg/kg and HBwI 90.0 µg/kg; severe bleeds in HAwI 82.0 µg/kg and HBwI 68.0 µg/kg). In people with HA, bleeds were managed with factor VIII (median consumption per injection: mild/moderate bleeds 20.0 IU/kg; severe bleeds 20.9 IU/kg) and in people with HB with factor IX (mild/moderate bleeds 30.0 IU/kg; severe bleeds 28.9 IU/kg).

Conclusion(s): BTBs that occurred in patients receiving concizumab prophylaxis were mostly of mild/moderate severity and could be effectively treated in alignment with the trial protocol guidance provided. Most mild/moderate bleeds were resolved with a single injection of factor or bypassing agent.