Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis

Abstract

The efficacy and safety of caplacizumab in individuals with acquired thrombotic thrombocytopenic purpura (aTTP) have been established in the phase 2 TITAN and phase 3 HERCULES trials. Integrated analysis of data from both trials was conducted to increase statistical power for assessing treatment differences in efficacy and safety outcomes. Caplacizumab was associated with a significant reduction in the number of deaths (0 vs 4; P < .05) and a significantly lower incidence of refractory TTP (0 vs 8; P < .05) vs placebo during the treatment period. Consistent with the individual trials, treatment with caplacizumab resulted in a faster time to platelet count response (hazard ratio, 1.65; P < .001), a 72.6% reduction in the proportion of patients with the composite end point of TTP-related death, TTP exacerbation, or occurrence of at least 1 treatment-emergent major thromboembolic event during the treatment period (13.0% vs 47.3%; P < .001), and a 33.3% reduction in the median number of therapeutic plasma exchange days (5.0 vs 7.5 days) vs placebo. No new safety signals were identified; mild mucocutaneous bleeding was the main safety finding. This integrated analysis provided new evidence that caplacizumab prevents mortality and refractory disease in acquired TTP and strengthened individual trial findings, with a confirmed favorable safety and tolerability profile. These trials were registered at www.clinicaltrials.gov as #NCT01151423 and #NCT02553317.

Conflict of interest statement

Conflict-of-interest disclosure: F.P. served as a consultant for Kedrion, received honoraria for being a speaker at educational meetings from Ablynx/Sanofi, Grifols, Novo Nordisk, Roche, Shire, and Sobi, and was a member of an advisory board for Ablynx/Sanofi. S.C. received research funding and consulting fees from Ablynx/Sanofi and Alexion. M.S. served on advisory boards and received speaker fees from Ablynx/Sanofi, Alexion, Shire, and Novartis, and received research funding from Shire. P.C. was a member of advisory boards for and received speaker fees from Ablynx/Sanofi, Alexion, Octapharma, and Shire. P.K. served as a consultant, was a member of an advisory board, and received speaker fees from Ablynx/Sanofi, Shire, CSL Behring, Roche, and Novo Nordisk, and received research funding as unrestricted educational grants from Novo Nordisk. J.A.K.H. received research funding from Shire, received honoraria (to employer, Insel Gruppe AG, Department of Hematology) for participation in advisory boards and presentations from Ablynx/Sanofi, CSL Behring, Roche, Shire, and Siemens. A.M. served as a consultant for Ablynx/Sanofi. J.d.l.R. served as a consultant for Ablynx/Sanofi, Amgen, Celgene, and Janssen, and provided expert testimony for Amgen, Celgene, and Janssen. K.P. received research funding for participation in clinical trials from Ablynx (a Sanofi company), Bioverativ (a Sanofi company), Alexion, and Octapharma, and received honoraria for participation in advisory boards and presentations from Ablynx (a Sanofi company), Shire, and Alexion. J.M.M.E. is an employee with Ablynx/Sanofi. H.D.W. was an employee with Ablynx/Sanofi when this research was conducted. F.C. is employed by Sanofi (and was formerly employed by Ablynx/Sanofi).

© 2021 by The American Society of Hematology.

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Graphical abstract