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1754 Caplacizumab Induces Fast and Durable Platelet Count Responses with Improved Time to Complete Remission and Recurrence-Free Survival in Patients with Acquired Thrombotic Thrombocytopenic PurpuraClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 311. Disorders of Platelet Number or Function: Poster II
Hematology Disease Topics & Pathways:
Diseases, Bleeding and Clotting, platelets, Biological Processes, Cell Lineage, Thrombotic Disorders, immune mechanism
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Paul Coppo1*, Marie Scully, MD2, Javier de la Rubia3,4*, Flora Peyvandi5,6, Spero Cataland7, Johanna A Kremer Hovinga Strebel8*, Paul Knoebl9*, Katerina Pavenski, MD10*, Jessica Minkue Mi Edou11*, Filip Callewaert12* and Rui de Passos Sousa13*

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


Acquired thrombotic thrombocytopenic purpura (aTTP) is characterized by disseminated platelet-rich microvascular occlusions throughout the body. Rapid control of platelet consumption and maintaining durable remission are key therapeutic goals. Many patients with aTTP experience exacerbation despite daily therapeutic plasma exchange (TPE) and immunosuppression.

In the Phase 3 HERCULES trial (NCT02553317), caplacizumab treatment resulted in a significantly faster time to platelet count normalization compared with placebo. Although some placebo-treated patients achieved a fast platelet count response, many subsequently progressed to rapid exacerbation of disease. The aim of this study is to characterize the durability of platelet count responses in the HERCULES trial.


In this post hoc analysis of the HERCULES intent-to-treat population (caplacizumab, n=72; placebo, n=73), we identified patients with a fast platelet count response (ie, ≤3 days vs >3 days) and described the exacerbation rate by treatment group. Time to durable platelet count response (defined as time to last daily TPE during the overall treatment period), time to complete remission (defined as platelet count >150×109/L and lactate dehydrogenase <1.5× the upper limit of normal for >30 days after cessation of daily TPE), and recurrence-free survival (absence of exacerbation or relapse during the overall study period) were calculated.


More than half of the patients in the HERCULES trial achieved an initial platelet count normalization within 3 days (caplacizumab, 56/72 [78%]; placebo, 43/73 [59%]). In patients with a fast platelet count response (ie, ≤3 days), the exacerbation rate was 3.6% (2/56) with caplacizumab and 44.2% (19/43) with placebo, suggesting that the rapid platelet count response was sustained with caplacizumab, whereas almost half of the fast responders in the placebo group subsequently exacerbated. In patients with time to platelet count response >3 days, the exacerbation rate was 6.7% (1/15) with caplacizumab and 30.0% (9/30) with placebo, confirming the durable response with caplacizumab. The exacerbation rate among placebo patients with platelet response >3 days remained high but was numerically lower compared with fast responders. Of the patients who experienced exacerbations, 90% (2/3 in the caplacizumab group and 26/28 in the placebo group) switched to open-label caplacizumab, which may have favored the outcomes of placebo patients. Despite this bias, the median (95% confidence interval [CI]) time to durable response was 4.5 (4.4–4.6) days with caplacizumab and 10.5 (6.5–14.5) days with placebo (Figure 1A); accordingly, the median (95% CI) time to complete remission was shorter in the caplacizumab group (40.0 [37.7–41.1] days) compared with placebo (44.2 [42.0–48.2] days) (Figure 1B). The analysis of overall recurrence-free survival during the entire study period demonstrated an early and sustained benefit for caplacizumab over placebo (Figure 1C), mainly driven by significant reduction in exacerbations during the study drug treatment period. The effect was sustained, despite 6 relapses in the caplacizumab group in the follow-up period in patients with unresolved underlying autoimmune disease activity.


Caplacizumab demonstrated a faster and sustained platelet count response compared with the placebo group, in which many fast responders subsequently had an exacerbation. Fast platelet count responses with caplacizumab were maintained and translated into clinically relevant improvements in time to complete remission and overall recurrence-free survival.


This research was funded by Ablynx, a Sanofi company.

Disclosures: Coppo: Shire/Takeda: Other: Advisory Board, Speakers Bureau; Ablynx, a Sanofi company: Other: Advisory Board, Speakers Bureau; Alexion: Other: Advisory Board, Speakers Bureau. Scully: Alexion: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Takeda: Speakers Bureau; Ablynx/Sanofi: Consultancy, Other: Advisory Board, Speakers Bureau; Shire/Takeda: Other: Advisory Board, Research Funding, Speakers Bureau; Novartis: Other: Advisory Board, Speakers Bureau. de la Rubia: Ablynx/Sanofi: Consultancy, Other: Expert Testimony; Amgen: Consultancy, Other: Expert Testimony; Celgene: Consultancy, Other: Expert Testimony; Janssen: Consultancy, Other: Expert Testimony. Peyvandi: Octapharma: Research Funding. Cataland: Alexion: Consultancy, Research Funding; Ablynx/Sanofi: Consultancy, Research Funding. Kremer Hovinga Strebel: SHIRE/TAKEDA: Membership on an entity's Board of Directors or advisory committees, Other: advisory board, Research Funding; Ablynx/Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: advisory board, Speakers Bureau; Ablynx/Sanofi: Other: Advisory Board, Speakers Bureau; Shire/Takeda: Other: Advisory Board, Research Funding; CSL Behring: Speakers Bureau; Roche: Speakers Bureau; Siemens: Speakers Bureau. Knoebl: Shire/Takeda: Other: Advisory Board, Speakers Bureau; Ablynx/Sanofi: Other: Advisory Board, Speakers Bureau; CSL Behring: Other: Advisory Board, Speakers Bureau; Roche: Other: Advisory Board, Speakers Bureau; Novo Nordisk: Other: Advisory Board, Research Funding, Speakers Bureau. Pavenski: Sanofi: Research Funding; Alexion: Honoraria, Research Funding; Octapharma: Research Funding; Shire/Takeda: Honoraria; Bioverativ: Research Funding; Ablynx/Sanofi: Honoraria, Research Funding. Minkue Mi Edou: Sanofi: Current Employment. Callewaert: Sanofi: Current Employment. de Passos Sousa: Sanofi: Current Employment.

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