Befovacimab treatment does not appear to be safe in patients with hemophilia despite favorable initial preclinical and clinical results, according to a new study published in Haemophilia.
This is based on the results of a multiple-dose, dose-escalating phase 2 clinical trial that had to be terminated early due to thrombosis.
During the trial, 24 patients with hemophilia were treated with 100 mg, 225 mg, or 400 mg of subcutaneous befovacimab once a week for 2 to 47 weeks. The primary outcome was safety. Secondary outcomes included the annualized bleeding rate and the pharmacokinetics and pharmacodynamics of befovacimab.
Results from the trial showed that patients treated with 100 mg and 225 mg of befovacimab had improved bleeding control in a dose-dependent manner. However, during the trial, there were 3 drug-related thrombotic serious adverse events. Two were in the 225 mg group and 1 was in the 400 mg group. Following this, the trial was terminated prematurely.
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There were no bleeding episodes accompanying the thrombotic events. No patients were using concomitant replacement or bypass therapies. There were also no laboratory abnormalities, and the pharmacokinetic and pharmacodynamic data did not correlate with the occurrence of serious adverse events or the levels of circulating befovacimab or free tissue factor pathway inhibitor.
According to the authors of the study, this “raises concerns about the predictability of thrombosis.” They say that this finding underscores the need to further investigate the therapeutic window in which treatments like befovacimab should be used.
Befovacimab is a fully human monoclonal antibody that can bind to tissue factor pathway inhibitor, which normally reduces the body’s ability to form blood clots. By binding to and inhibiting the action of tissue factor pathway inhibitor, befovacimab aims to protect patients with hemophilia from bleeds. It was developed as a nonreplacement therapy for patients with hemophilia A or B with or without inhibitors.
Mancuso ME, Ingham SJM, Kunze M. Befovacimab, an anti-tissue factor pathway inhibitor antibody: early termination of the multiple-dose, dose-escalating phase 2 study due to thrombosis. Haemophilia. Published online June 6, 2022. doi:10.1111/hae.14595
Multiple escalating dose study of BAY1093884 in adults with hemophilia A or B with or without inhibitors. ClinicalTrials.gov. July 24, 2018. Updated November 30, 2020. Accessed June 14, 2022.