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Caplacizumab effective in acquired thrombotic thrombocytopenic purpura
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Patients with acquired thrombotic thrombocytopenic purpura experienced a faster normalization of platelet count when treated with caplacizumab than placebo, according to results of a randomized phase 3 trial published in The New England Journal of Medicine.
Those treated with caplacizumab (Cablivi, Ablynx) also experienced lower incidence of disease-related death and recurrence.
Caplacizumab, a bivalent anti-von Willebrand factor nanobody, has been approved in the European Union for treatment of adults with acquired thrombotic thrombocytopenic purpura.
The agent has not yet been approved in the United States. However, the FDA accepted the biologics license application for caplacizumab and granted it priority review, setting a target action date of Feb. 6, Marie Scully, MD, professor of hematology at University College London Hospitals, told HemOnc Today.
The double-blind HERCULES trial included 145 patients (median age, 46 years; range 18-79; 69% women; 67% white) with acquired thrombotic thrombocytopenic purpura.
Scully and colleagues randomly assigned patients to standard treatment with daily plasma exchange and glucocorticoids plus either caplacizumab (n = 72) or placebo (n = 73).
Patients in the caplacizumab group received a 10 mg IV loading bolus followed by 10 mg daily subcutaneously.
Time to platelet count normalization served as the primary endpoint. Secondary endpoints included a composite of acquired thrombotic thrombocytopenic purpura-related death, disease recurrence or a thromboembolic event during the treatment period; refractory disease; and normalization of organ-damage markers.
Median time to normalization of platelet count in the caplacizumab group of 2.69 days (95% CI, 1.89-2.83) compared with 2.88 days (95% CI, 2.68-3.56) in the placebo group.
Patients treated with caplacizumab had a 1.55 times greater likelihood of achieving platelet count normalization, 67% lower incidence of recurrence (12% vs. 38%; P < .001) and 74% lower incidence of a composite outcome event (12% vs. 49%; P < .001) than patients in the placebo group.
Patients in the caplacizumab group needed less plasma exchange and had shorter hospital stays than patients in the placebo group.
No patients in the caplacizumab group developed refractory disease, compared with three in the placebo group.
A total of 129 patients (caplacizumab, n = 65; placebo, n = 64) had platelet count normalization and completed the daily plasma exchange period. However, 28 patients in the placebo group had recurrence within 30 days of ending daily plasma exchange, compared with three patients in the caplacizumab group.
The most common adverse event, mucocutaneous bleeding, occurred among 65% of the caplacizumab group and 48% of the placebo group.
Three patients in the placebo group died during the treatment period. One patient in the caplacizumab group died of cerebral ischemia after the treatment period.
“Over the past two decades, despite a better understanding of the pathophysiological characteristics of acquired thrombotic thrombocytopenic purpura, treatment outcomes have not changed substantially, with recent mortality rates reported to be as high as 20%,” Scully and colleagues wrote. “Overall, caplacizumab showed value when added to the standard treatment for acquired thrombotic thrombocytopenic purpura.”– by John DeRosier
For more information:
Marie Scully, MD, can be reached at m.scully@nhs.net.
Disclosures: Ablynx funded this study. Scully reports research funding and personal fees from Ablynx, advisory roles with Alexion, Novartis and Shire, and research funding from Baxalta. Please see the study for all other authors’ relevant financial disclosures.
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