Long-term follow-up of patients treated with caplacizumab and safety and efficacy of repeat caplacizumab use: Post-HERCULES study

Marie Scully; Javier de la Rubia; Katerina Pavenski; Ara Metjian; Paul Knöbl; Flora Peyvandi; Spero Cataland; Paul Coppo; Johanna A Kremer Hovinga; Jessica Minkue Mi Edou; Rui De Passos Sousa; Filip Callewaert; Sriya Gunawardena; Julie Lin

doi:10.1111/jth.15892

Long-term follow-up of patients treated with caplacizumab and safety and efficacy of repeat caplacizumab use: Post-HERCULES study

J Thromb Haemost. 2022 Dec;20(12):2810-2822. doi: 10.1111/jth.15892. Epub 2022 Oct 21.

Authors

Marie Scully^{1

2}, Javier de la Rubia³, Katerina Pavenski⁴, Ara Metjian⁵, Paul Knöbl⁶, Flora Peyvandi⁷, Spero Cataland⁸, Paul Coppo⁹, Johanna A Kremer Hovinga¹⁰, Jessica Minkue Mi Edou¹¹, Rui De Passos Sousa¹², Filip Callewaert¹³, Sriya Gunawardena¹⁴, Julie Lin¹⁴

Affiliations

¹ Department of Haematology, UCLH and NIHR Cardiometabolic BRC, UCLH/UCL, London, UK.
² University College London Hospitals, London, UK.
³ Hematology Department, Internal Medicine, School of Medicine and Dentistry, Catholic University of Valencia and Hospital LA FE, Valencia, Spain.
⁴ Departments of Medicine and Laboratory Medicine, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada.
⁵ Division of Hematology, Department of Medicine, University of Colorado-Anschutz Medical Center, Denver, Colorado, USA.
⁶ Division of Hematology and Hemostasis, Department of Medicine 1, Medical University of Vienna, Vienna, Austria.
⁷ Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Università degli Studi di Milano, Milan, Italy.
⁸ Department of Internal Medicine, Ohio State University, Columbus, Ohio, USA.
⁹ Department of Hematology, Reference Center for Thrombotic Microangiopathies (CNR-MAT), Saint-Antoine University Hospital, AP-HP, Paris, France.
¹⁰ Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹¹ Formerly Sanofi, Zwijnaarde, Belgium.
¹² Formerly Sanofi, Lisbon, Portugal.
¹³ Formerly Sanofi, Diegem, Belgium.
¹⁴ Sanofi, Cambridge, Massachusetts, USA.

Abstract

Introduction: Caplacizumab demonstrated efficacy and safety in patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) in the phase 3 HERCULES trial. However, data on long-term outcomes following caplacizumab treatment are limited.

Objectives: The post-HERCULES trial (NCT02878603) evaluated long-term outcomes of patients with iTTP treated with caplacizumab in HERCULES and safety and efficacy of repeated caplacizumab use.

Patients/methods: Over 3 years of follow-up, patients could receive open-label caplacizumab with therapeutic plasma exchange (TPE) and immunosuppressive therapy (IST) in case of recurrence. Adverse events (AEs) were assessed during the overall study period (intention-to-observe [ITO] population) and during recurrences (recurrence population). TTP-related events (TTP-related death, recurrence, major thromboembolic events) were assessed in the efficacy ITO population (patients without recurrence during HERCULES or before post-HERCULES).

Results: Among 104 enrolled patients, incidences of AEs and serious AEs were similar between patients who had received caplacizumab + TPE + IST during HERCULES (n = 75) and those treated with placebo + TPE + IST (placebo; n = 29). TTP-related events occurred in 8% of patients (4/49) randomized to caplacizumab during HERCULES versus 38% (11/29) randomized to placebo. Nineteen patients had ≥1 recurrence; 13 of these were treated with caplacizumab. The first recurrence episode was resolved or resolving for all patients treated with caplacizumab, including nine patients with repeat caplacizumab use. All second recurrences (6/6) were resolved. Safety profile of caplacizumab for treatment of recurrence was consistent with HERCULES; most bleeding events were nonserious. No major cases of organ dysfunction were observed.

Conclusions: Long-term follow-up supports the safety and efficacy of caplacizumab for iTTP and its repeated use for recurrences.

Keywords: blood platelets; caplacizumab; follow-up studies; thrombotic thrombocytopenic purpura; von Willebrand factor.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

ADAMTS13 Protein / therapeutic use
Follow-Up Studies
Humans
Purpura, Thrombotic Thrombocytopenic*
Single-Domain Antibodies* / therapeutic use

Substances

ADAMTS13 Protein
caplacizumab
Single-Domain Antibodies
thiamine triphosphorate

Associated data

ClinicalTrials.gov/NCT02878603