French pharmaceutical giant Sanofi recently announced that the US Food and Drug Administration (FDA) has approved the nanobody drug Cablivi (caplacizumab), combined with plasma exchange and immunosuppressive therapy. For the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP). The approval makes Cablivi the first drug in the United States to specialize in the treatment of aTTP. This drug was also approved by the European Union at the end of August 2018 for adult patients who have experienced an aTTP attack. In the United States and the European Union, it has been granted orphan drug qualifications for the treatment of aTTP as well as fast-track qualifications and priority review qualifications in the United States.

aTTP is a life-threatening, autoimmune-based coagulation disorder characterized by the formation of large amounts of blood clots in small blood vessels throughout the body. Leading to severe thrombocytopenia (extremely low platelet count), microangiopathy hemolytic anemia (loss of red blood cells due to hemolytic destruction), tissue ischemia (limited blood supply in parts of the body) and extensive organ damage, especially the brain and heart. Despite current standard care regimens, including daily plasmapheresis (PEX) and immunosuppressive therapy, patients still face a high risk of thrombotic complications, recurrence and death. aTTP still has a mortality rate of up to 20 per cent, most of which occur within 30 days of diagnosis.

The active drug component of Cablivi is caplacizumab, which is a potent and selective bivalent anti-von Willebrand factor (vWF) nanobody, which can block the interaction between multimers of ultra-large von Willebrand factor (ULvWF) and platelets. It has an immediate effect on platelet aggregation and the subsequent formation and accumulation of small blood clots (microclot). In patients with aTTP, this tiny blood clot can lead to severe thrombocytopenia, tissue ischemia, and organ dysfunction. This immediate effect of Cablivi can not only dismantle the potential disease process, but also protect the clinical manifestations of aTTP patients.

The approval of Cablivi was based on data from the Phase III Clinical study HERCULES (NCT02553317). The study was a randomized, double-blind, placebo-controlled study of 145 adult patients with aTTP. In the study, patients were randomly assigned to Cablivi or placebo and received standard care regimens (plasma exchange and immunosuppressive therapy). Marie Scully, a professor of hematology at the University of London Hospital and lead researcher of the HERCULES study, previously said, “aTTP is a life-threatening disease and the current treatment does not completely prevent widespread thrombosis in small blood vessels throughout the body. This puts patients at risk of serious morbidity and premature death. Our research shows that Cablivi has the potential to address significant unmet medical needs in this area and to help patients facing potentially devastating consequences. “