LONG-TERM OUTCOMES OF PATIENTS TREATED WITH CAPLACIZUMAB FOR IMMUNE-MEDIATED THROMBOTIC THROMBOCYTOPENIC PURPURA (ITTP): THE POST-HERCULES STUDY

Abstract

The efficacy and safety of caplacizumab (CPLZ) for patients (pts) with immune-mediated thrombotic thrombocytopenic purpura (iTTP; also known as acquired TTP) were demonstrated in the Phase 3 HERCULES trial, with a 28-day follow-up period after end of treatment. Post-HERCULES (NCT02878603) evaluated the long-term outcomes of pts with iTTP treated with CPLZ during HERCULES, and the safety and efficacy of repeated CPLZ use for iTTP recurrence. Over 3 years’ follow-up, pts could receive CPLZ with therapeutic plasma exchange (TPE) and immunosuppressive therapy (IST) for iTTP recurrence. Safety was assessed during the overall study period in the intention-to-observe (ITO) population; TTP-related events (TTP-related mortality, recurrence, or major thromboembolic events) were assessed in pts without recurrence in HERCULES or prior to post-HERCULES (efficacy ITO population). Safety and efficacy were also evaluated during recurrences. Of 104 pts enrolled, incidences of adverse events (AEs) were similar between pts treated with CPLZ+TPE+IST during HERCULES (n=75) and pts treated with TPE+IST only (n=29). TTP-related events occurred in 4/49 pts (8%) randomized to CPLZ vs 11/29 pts (38%) randomized to placebo. The first recurrence episode was resolved/resolving for all 13 pts treated with CPLZ for recurrence, including 9 pts with repeat CPLZ. The safety profile of CPLZ for recurrence was consistent with HERCULES. Over long-term follow-up, the safety profile of patients treated with CPLZ in combination with TPE+IST was generally similar to those who received IST+TPE only, with no observed increases in iTTP recurrence. Repeat use of CPLZ was efficacious, with no new safety concerns.