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

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.

• Authors: 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
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 20 Issue 12 Pg. 2810-2822 (12 2022) ISSN: 1538-7836 [Electronic] England
• PMID: 36138517 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Sanofi and The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.

Chemical References

• ADAMTS13 Protein
• caplacizumab
• Single-Domain Antibodies
• thiamine triphosphorate

Topics

• Humans
• ADAMTS13 Protein (therapeutic use)
• Follow-Up Studies
• Purpura, Thrombotic Thrombocytopenic
• Single-Domain Antibodies (therapeutic use)