General Information

Cablivi (caplacizumab-yhdp) is a von Willebrand factor (vWF)-directed antibody fragment. Caplacizumab blocks the interaction of ultralarge von Willebrand Factor (vWF) multimers with platelets and, therefore, has an immediate effect on platelet adhesion and the ensuing formation and accumulation of the micro-clots that cause the severe thrombocytopenia, tissue ischemia and organ dysfunction in aTTP.

Cablivi is specifically indicated for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.

Cablivi is supplied as an injection for intravenous or subcutaneous administration. Cablivi should be administered upon initiation of plasma exchange therapy. The recommended dose of Cablivi is as follows: First day of treatment: 11 mg bolus intravenous injection at least 15 minutes prior to plasma exchange followed by an 11 mg subcutaneous injection after completion of plasma exchange on day 1. Subsequent days of treatment during daily plasma exchange: 11 mg subcutaneous injection once daily following plasma exchange. Treatment after plasma exchange period: 11 mg subcutaneous injection once daily continuing for 30 days following the last daily plasma exchange. If after initial treatment course, sign(s) of persistent underlying disease such as suppressed ADAMTS13 activity levels remain present, treatment may be extended for a maximum of 28 days. Discontinue Cablivi if the patient experiences more than 2 recurrences of aTTP, while on Cablivi.

If a dose of Cablivi is missed during the plasma exchange period, it should be given as soon as possible. If a dose of Cablivi is missed after the plasma exchange period, it can be administered within 12 hours of the scheduled time of administration. Beyond 12 hours, the missed dose should be skipped and the next daily dose administered according to the usual dosing schedule.

Clinical Results

FDA Approval

The FDA approval of Cablivi was based on the HERCULES trial, a phase III pivotal multicenter, randomized, double-blind, placebo-controlled trial conducted in 145 subjects with acquired thrombotic thrombocytopenic purpura (aTTP). The subjects were randomized to either Cablivi (n=72) or placebo (n=73). Subjects in both groups received plasma exchange and immunosuppressive therapy. In the HERCULES study, treatment with caplacizumab in addition to standard-of-care resulted in a significantly shorter time to platelet count response (p<0.01), the study's primary endpoint; a significant reduction in aTTP-related death, recurrence of aTTP, or at least one major thromboembolic event during study drug treatment (p<0.0001); and a significantly lower number of aTTP recurrences in the overall study period (p<0.001). Importantly, treatment with caplacizumab resulted in a clinically meaningful reduction in the use of PEX and length of stay in the intensive care unit (ICU) and the hospital, compared to the placebo group.