Caplacizumab (Cablivi), an Anti VWF, is a humanized monoclonal antibody fragment that binds to von Willebrand factor (VWF) and blocks VWF interaction with platelet GPlb-IX-V. Evidence to support its effectiveness in TTP comes from the HERCULES and TITAN trials that randomly assigned 145 patients (mostly adults) with acquired TTP to receive caplacizumab or placebo daily until 30 days beyond the last PEX procedure. The diagnosis of TTP was based on clinical presentation (thrombocytopenia and microangiopathic hemolysis); severe ADAMTS13 deficiency was not a criterion for entry but was subsequently documented in all but seven of the patients. All patients received daily PEX and glucocorticoids and could receive other immunosuppressive therapies. Slightly less than half received rituximab. Individuals who had an exacerbation could be switched to open-label caplacizumab. Compared with placebo, caplacizumab was associated with the outcomes:
- Fewer deaths (1 versus 3 [1 versus 4 percent])
- Faster normalization of the platelet count (rate ratio 1.55; 95% CI 1.09-2.19), which correlated with fewer days of PEX (mean, 5.8 versus 9.4)
- Fewer exacerbations in the 30 days after stopping PEX (12 versus 38 percent)
- Shorter hospitalization (mean, 9.9 versus 14.4 days) and fewer days in the intensive care unit (mean, 3.4 versus 9.7)
Caplacizumab was today approved by FDA in US (Link).
Common side effects of Cablivi reported by patients in clinical trials were bleeding of the nose or gums and headache. The prescribing information for Cablivi includes a warning to advise health care providers and patients about the risk of severe bleeding.