Population Pharmacokinetics and Exposure-Response Analyses to Demonstrate the Link of Causality between ADAMTS13 and the Clinical Effects of Recombinant ADAMTS13 Compared to Plasma-Based Therapies

Background:Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare, life-threatening deficiency of ADAMTS13. TTP clinical manifestations include thrombocytopenia and microangiopathic hemolytic anemia (MAHA) but incomplete understanding of their relationship to ADAMTS13 exposure is a challenge for assessing the impact of ADAMTS13 supplementation. Integrated population pharmacokinetics (PopPK) analysis and exposure-response modeling were conducted to support the clinical benefit assessment of recombinant ADAMTS13 (rADAMTS13; Takeda Development Center Americas, Inc., Lexington, MA, USA) in patients with cTTP.