ABLYNX INITIATES A SINGLE AND MULTIPLE DOSE PHASE I STUDY OF CAPLACIZUMAB IN HEALTHY JAPANESE SUBJECTS - Seite 2

The efficacy and safety of caplacizumab in conjunction with the standard of care of plasma exchange (PEX) and immunosuppression, were evaluated in the Phase II TITAN study in 75 patients with aTTP. Caplacizumab was well-tolerated and the primary endpoint was met (p=0.005), with caplacizumab treatment resulting in a 39% reduction in time to platelet count normalisation as compared to placebo (i.e., a faster reversion of thrombocytopenia with consequent reduced use of PEX)^[1]. Moreover, during treatment, caplacizumab reduced recurrences of aTTP by 71% compared to placebo^[2]. Post-hoc analyses of the Phase II TITAN study data were performed to assess the impact of caplacizumab on a composite endpoint of major thromboembolic complications and aTTP-related mortality, as well as on refractoriness to standard treatment. The results demonstrate that a clinically meaningful lower proportion of subjects treated with caplacizumab experienced one or more major thromboembolic events, or died, as compared to placebo (11.4% versus 43.2%)². In addition, fewer caplacizumab-treated patients, compared to those who received placebo, were refractory to treatment (5.7% versus 21.6%)^{2, [3]}. There were two deaths in the placebo group and both of those patients were refractory to treatment; no deaths were reported in the caplacizumab group.

The randomised, double-blind, placebo-controlled Phase III HERCULES study (NCT02553317) will evaluate the efficacy and safety of caplacizumab in patients with aTTP when administered in addition to the standard-of-care. The primary endpoint is time to platelet count normalisation, a measure of prevention of further microvascular thrombosis. Key secondary endpoints include a composite endpoint consisting of TTP-related mortality, recurrence of TTP and major thromboembolic events during study drug treatment, as well as the prevention of recurrence of TTP during the study period, refractoriness to treatment, and the effect on biomarkers of organ damage. Results from this Phase III study are expected in the second half of 2017 and these results are expected to support a BLA filing in the United States in 2018. A Marketing Authorisation Application (MAA) has already been submitted to the European Medicines Agency (EMA) for approval of caplacizumab in aTTP^[4]. If approved by regulatory authorities, caplacizumab will be the first therapeutic specifically indicated for the treatment of aTTP.