An integrated analysis based on the Phase 2 TITAN (NCT01151423) and Phase 3 HERCULES (NCT02553317) studies with caplacizumab (CPLZ) in acquired thrombotic thrombocytopenic purpura (aTTP) was performed to assess treatment differences on efficacy and safety outcomes that may have been undetected in the individual trials.

In both trials, patients with an acute episode of aTTP were randomized to receive CPLZ or placebo (PBO) in addition to therapeutic plasma exchange (TPE) and immunosuppression. All randomized patients from both studies were included in the integrated efficacy analyses (CPLZ: n=108; PBO: n=112), and those who received at least 1 dose of the study drug were included in the safety analyses (CPLZ: n=106; PBO: n=110).

CPLZ significantly reduced mortality (0 vs 4 deaths; P<0.05) and refractory TTP (0 vs 8 events; P<0.05) versus PBO and improved time to platelet count response (hazard ratio, 1.65; P<0.001). CPLZ also reduced the composite endpoint of TTP-related death, exacerbation, or any treatment-emergent major thromboembolic event during the treatment period (13.0% vs 47.3%; P<0.001) and median number of TPE days (5.0 vs 7.5 days) versus PBO. Mild mucocutaneous bleeding was the main safety finding for CPLZ.

This integrated analysis provided new evidence that CPLZ prevents mortality and refractory disease in aTTP and reinforced the individual trial efficacy and safety findings. No new safety signals were identified for