The European Commission has granted marketing authorization for caplacizumab (Cablivi), a humanized bivalent nanobody that inhibits the interaction between von Willebrand factor and platelets.
Caplacizumab is now approved to treat adults with acquired thrombotic thrombocytopenic purpura (aTTP) in all member countries of the European Union as well as Norway, Iceland, and Liechtenstein.
The drug has been accepted for priority review in the United States and the Food and Drug Administration is expected to make a decision by Feb. 6, 2019.
The European Commission’s approval of caplacizumab is supported by data from the phase 2 TITAN study and the phase 3 HERCULES study.
The TITAN trial included 75 aTTP patients who were randomized to caplacizumab (n = 36) or placebo (n = 39), with all patients receiving the current standard of care – daily plasma exchange and immunosuppressive therapy (N Engl J Med. 2016;374:511-22).
Patients in the caplacizumab arm had a 39% reduction in the median time to response, compared with patients in the placebo arm (P = .005).
The rate of adverse events (AEs) thought to be related to the study drug was 17% in the caplacizumab arm and 11% in the placebo arm. The rate of AEs that were possibly related was 54% and 8%, respectively. The rate of serious AEs was 37% and 32%, respectively.
There were no deaths in the caplacizumab arm and two in the placebo arm. One death was attributable to severe, refractory TTP, and the other was attributable to cerebral hemorrhage.Results from the HERCULES trial were presented at the 2017 annual meeting of the American Society of Hematology.
The study enrolled patients with an acute episode of aTTP. They were randomized to receive caplacizumab (n = 72) or placebo (n = 73) in addition to standard care – plasma exchange and immunosuppression.
The study’s primary endpoint was the time to platelet count response (normalization). There was a significant reduction in time to platelet count response in the caplacizumab arm, compared with the placebo arm. The platelet normalization rate ratio was 1.55 (P less than .01).
A secondary endpoint was the combination of aTTP-related death, aTTP recurrence, and at least one major thromboembolic event during study treatment. The incidence of this combined endpoint was 12.7% (n = 9) in the caplacizumab arm and 49.3% (n = 36) in the placebo arm (P less than .0001).
The incidence of aTTP-related death was 0% (n = 0) in the caplacizumab arm and 4.1% (n = 3) in the placebo arm. The incidence of aTTP recurrence was 4.2% (n = 3) in the caplacizumab arm and 38.4% in the placebo arm (n = 28), and the incidence of at least one major thromboembolic event was 8.5% (n = 6) and 8.2% (n = 6), respectively.