New results from the phase 3 HERCULES study (ClinicalTrials.gov Identifier: NCT02553317) show that open-label caplacizumab appears to be safe and efficacious in patients with acquired thrombotic thrombocytopenic purpura (aTTP) who experience a disease exacerbation.

During the double-blind trial, patients with aTTP received caplacizumab or placebo with daily therapeutic plasma exchange (TPE) and for at least 30 subsequent days. If patients had an exacerbation, defined as disease recurrence within 30 days after completion of daily TPE, during double-blind treatment, they were permitted to switch to open-label caplacizumab and reinitiate daily TPE.

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The new report, which was published in the Journal of Thrombosis and Haemostasis, describes the safety and efficacy of open-label caplacizumab in patients who switched to it from double-blind treatment.

During the double-blind period, the rate of exacerbation was higher in the placebo group compared with the caplacizumab group (38% vs 4%). Of 31 patients (placebo, 28 patients; caplacizumab, 3 patients) who had an exacerbation, 28 patients switched to open-label caplacizumab (placebo, 26 patients; caplacizumab, 2 patients) and 3 patients discontinued treatment. At the time of exacerbation, 25 of the 28 patients from the placebo group and all 3 patients from the caplacizumab group had low ADAMTS13 activity (below 10%).

Upon initiation of open-label caplacizumab, median time to platelet count response (≥ 150 x 109/L) was 3.49 days and median time to daily TPE cessation was 6.0 days.

During open-label treatment, 1 patient experienced a major thromboembolic event (vena cava thrombosis), and 1 patient had another exacerbation event. Catheter site hemorrhage (28.6%), headache (21.4%), and epistaxis (17.9%) were the most frequent treatment-emergent adverse events. No deaths occurred.

The investigators concluded, “These results from the open-label phase of HERCULES thus confirm the efficacy and safety of caplacizumab in controlling platelet consumption and aTTP propagation, even when patients are in an exacerbating state, and demonstrate improved outcomes for aTTP patients.”

Reference

1.     Knoebl P, Cataland S, Peyvandi F, et al. Efficacy and safety of open‐label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study [published online 5, 2019]. J Thromb Haemost. doi:10.1111/jth.14679