Caplacizumab-yhdp, a bivalent anti–von Willebrand factor nanobody, was approved for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.
The U.S. Food and Drug Administration’s decision was based on results from the multicenter, randomized, double-blind, placebo-controlled HERCULES trial, which randomized 145 patients to receive either caplacizumab-yhdp (n=72) or placebo (n=73). All participants also received plasma exchange and immunosuppressive therapy.
Per study protocol, patients received caplacizumab-yhdp 11 mg or placebo as a single 11-mg bolus intravenous injection prior to the first plasma exchange, followed by a daily subcutaneous injection of caplacizumab-yhdp or placebo after completion of plasma exchange, for the duration of the daily plasma exchange period and for 30 days subsequently. If patients had persistent signs of aTTP (such as suppressed ADAMTS13 activity levels), treatment was extended for seven-day intervals for a maximum of 28 days.
In patients who received caplacizumab-yhdp, the time to platelet-count response (defined as a platelet count ≥150×109 /L plus cessation of daily plasma exchange within 5 days) was significantly shorter than those who received placebo: 2.69 days (95% CI 1.89-2.83] versus 2.88 days (95% CI 2.68-3.56; p=0.01).
Caplacizumab-yhdp also resulted in a lower number of TTP-related deaths (0 vs. 3; p<0.001) and TTP recurrence (3 vs. 28; p<0.001) during the treatment period.
The most common adverse events (occurring ≥15% of patients) associated with caplacizumab-yhdp were epistaxis, headache, and gingival bleeding.
The agent was approved through priority review and with orphan product designation.
Source: FDA news release, February 6, 2019.