The Food and Drug Administration has approved caplacizumab (Cablivi) in combination with plasma exchange and immunosuppressive therapy for the treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP).
Caplacizumab is an anti–von Willebrand factor nanobody designed to inhibit the interaction between von Willebrand factor and platelets. The injection previously received orphan drug designation from the FDA and was approved under priority review.
The FDA’sof caplacizumab was based on results from the phase 3 HERCULES trial ( ).
The trial () included 145 adults with aTTP. They were randomized to receive caplacizumab (n = 72) or placebo (n = 73), in addition to plasma exchange and immunosuppression.
The study’s primary endpoint was the time to platelet count response (normalization), which was defined as a platelet count of at least 150 x 109/L with subsequent stop of daily plasma exchange within 5 days.
There was a significant reduction in time to platelet count response in the caplacizumab arm, compared with the placebo arm – 2.69 days and 2.88 days, respectively. 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% in the caplacizumab arm and 49% in the placebo arm (P less than .001).
The most common treatment-emergent adverse events (occurring in at least 15% of patients in the caplacizumab and placebo arms, respectively) were epistaxis (32% and 3%), headache (23% and 8%), urticaria (17% and 7%), and hypokalemia (9% and 19%).
During the treatment period, there were no deaths in the caplacizumab arm and three deaths in the placebo arm. There was one death (from cerebral ischemia) in the caplacizumab arm during the follow-up period, but it was considered unrelated to caplacizumab.
For more details on caplacizumab, see the.