CAPLACIZUMAB Anti-von Willebrand factor Treatment of acquired thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is characterized by the presence of multiple platelet-rich microthrombi. Patients with acquired TTP generate autoantibodies against the enzyme that regulates von Willebrand factor (vWF) multimer size, leading to the formation of ultralarge vWF multimers that produce vWF-rich microthrombi. TTP is treated using plasma exchange (TPX), although TPX is ineffective in 10-20% of patients. Caplacizumab is a first-in-class Nanobody (R) that binds the A1 region of vWF, preventing its adhesion to collagen and inhibiting the formation of microthrombi under high shear blood flow conditions. Preclinically, caplacizumab inhibited platelet aggregation and microthrombi formation in vitro and in vivo. Caplacizumab demonstrated favorable pharmacokinetics/pharmacodynamics in healthy volunteers with an acceptable safety profile. In patients with TTP undergoing TPX, caplacizumab significantly reduced the time to normalization of the platelet count compared with placebo. A phase III study to evaluate the safety and efficacy of caplacizumab in patients with TTP (HERCULES) is ongoing.