Positive results from the Phase 3 trial of caplacizumab (Cablivi; Sanofi) in adult patients with acquired thrombotic thrombocytopenia purpura (aTTP) were published in the New England Journal of Medicine.

Caplacizumab, an anti-von Willebrand factor (vWF) Nanobody, inhibits the interaction between ultra-large vWF multimers and platelets, thereby blocking the formation and buildup of micro-clots that cause thrombocytopenia, tissue ischemia, and organ dysfunction in patients with aTTP. In the HERCULES (NCT02553317) study patients with aTTP (N=145) were randomized to receive either caplacizumab or placebo in conjunction with plasma exchange and immunosuppression. The primary outcome of the study was the time to normalization of platelet count, with discontinuation of daily plasma exchange within 5 days thereafter. 

Results showed that the median time to platelet count normalization was shorter with caplacizumab vs placebo (2.69 days vs 2.88 days; P =.01); caplacizumab-treated patients were 1.55 times more likely to achieve normal platelet counts compared with those who received placebo. 

Moreover, compared with placebo, treatment with caplacizumab was associated with a lower incidence of a composite of aTTP-related death, recurrence of aTTP, or a thromboembolic event during the trial treatment period (74% reduction); and a lower rate of aTTP recurrence any time during the trial (67% reduction).

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The Food and Drug Administration (FDA) has accepted for priority review the Biologics License Application (BLA) for Cablivi for the treatment of patients aged ≥18 years experiencing an episode of aTTP. The Prescription Drug Fee User Act (PDUFA) target date has been set for February 6, 2019.

For more information visit nejm.org.