Efficacy and safety of open-label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study

Paul Knoebl, Spero Cataland, Flora Peyvandi, Paul Coppo, Marie Scully, Johanna A Kremer Hovinga, Ara Metjian, Javier de la Rubia, Katerina Pavenski, Jessica Minkue Mi Edou, Hilde De Winter, Filip Callewaert, Paul Knoebl, Spero Cataland, Flora Peyvandi, Paul Coppo, Marie Scully, Johanna A Kremer Hovinga, Ara Metjian, Javier de la Rubia, Katerina Pavenski, Jessica Minkue Mi Edou, Hilde De Winter, Filip Callewaert

Abstract

Background: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening autoimmune thrombotic microangiopathy. Caplacizumab, an anti-von Willebrand Factor Nanobody® , is effective for treating aTTP episodes and is well tolerated.

Objectives and methods: In the phase 3 HERCULES trial (NCT02553317), patients with aTTP received double-blind caplacizumab or placebo during daily therapeutic plasma exchange (TPE) and for ≥30 days thereafter. Patients who experienced an exacerbation while on blinded study drug treatment switched to receive open-label caplacizumab plus re-initiation of daily TPE. Exacerbations were defined as recurrence of disease occurring within 30 days after cessation of daily TPE.

Results: Thirty-one patients (placebo, n = 28; caplacizumab, n = 3) had an exacerbation during double-blind treatment. Twenty-eight patients switched to open-label caplacizumab (placebo, n = 26; caplacizumab, n = 2); the three others discontinued upon exacerbation. Median time to platelet count response (≥150 × 109 /L) was 3.49 days upon receiving caplacizumab. There were no deaths. During open-label treatment, further exacerbation or a major thromboembolic event (vena cava thrombosis) was experienced by one patient (3.6%) each. Consistent with the double-blind phase, the most frequent treatment-emergent adverse events were catheter site hemorrhage (28.6%), headache (21.4%), and epistaxis (17.9%).

Conclusions: These results suggest that caplacizumab was efficacious and well tolerated in patients with aTTP who experienced a disease exacerbation during double-blind treatment in HERCULES.

Keywords: ADAMTS13 protein; caplacizumab; plasma exchange; purpura; thrombotic thrombocytopenic; von Willebrand factor.

Conflict of interest statement

P. Knoebl reports consultancy (advisory board member/speaker fees) from Ablynx/Sanofi, Shire/Takeda, CSL‐Behring, Roche, and Novo Nordisk, and research funding (unrestricted educational grants) from Novo Nordisk; S. Cataland reports research funding and consulting fees from Ablynx/Sanofi and Alexion; F. Peyvandi reports consultancy for Kedrion; honoraria (speaker at educational meetings) from Ablynx/Sanofi, Grifols, Novo Nordisk, Roche, Shire and Sobi; and has been a member of an advisory board for Ablynx/Sanofi; P. Coppo has been a member of advisory boards for, and receipt of speaker fees from, Ablynx/Sanofi, Alexion, and Shire; M. Scully reports advisory boards and speaker fees from Ablynx/Sanofi, Alexion, Shire/Takeda, and Novartis, and research funding from Shire; J. A. Kremer Hovinga reports research funding from Shire and honoraria (to employer, Insel Gruppe AG, Department of Hematology) for participation in advisory boards/presentations from Ablynx/Sanofi, CSL‐Behring, Roche, Shire, and Siemens; A. Metjian reports consultancy for Ablynx/Sanofi; J. de la Rubia reports consultancy for Ablynx/Sanofi, AMGEN, Celgene, Janssen, and expert testimony for AMGEN, Celgene, and Janssen; K. Pavenski reports research funding (participation in clinical trials) from Ablynx, Bioverativ, Alexion, and Octapharma, and honoraria for participation in advisory boards/presentations from Ablynx, Shire, and Alexion; J. Minkue Mi Edou is employed by Ablynx, a Sanofi company; H. De Winter is employed by Ablynx, a Sanofi company, when this research was conducted; F. Callewaert is employed by Sanofi (formerly employed by Ablynx, a Sanofi company).

© 2019 Sanofi. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

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