Positive results from Phase III HERCULES study with caplacizumab for thrombotic thrombocytopenic purpura.- Ablynx.

Ablynx announced positive topline results from the Phase III HERCULES study with caplacizumab, the Company's anti-von Willebrand factor (vWF) Nanobody being developed for the treatment of acquired thrombotic thrombocytopenic purpura (aTTP). Treatment with caplacizumab in addition to standard-of-care resulted in a statistically significant reduction in time to platelet count response (p<0.01), the primary endpoint of the study and a measure of prevention of further microvascular thrombosis. patients on caplacizumab were 1.5 times more likely to achieve platelet count response at any given time point compared to patients treated with placebo.>

The Phase III HERCULES study also met the first two key secondary endpoints. Treatment with caplacizumab resulted in a 74% reduction in the percentage of patients with aTTP-related death, recurrence of aTTP, or at least one major thromboembolic event during study drug treatment (p<0.0001), with recurrences being the driver for achievement of this endpoint. in addition the proportion of patients with a recurrence of attp in the overall study period including the 28 day follow-up after discontinuation of study drug treatment was 67 lower in the caplacizumab arm compared to the placebo arm p><0.001), demonstrating the durability of the treatment effect. analysis of the third key secondary endpoint showed that no patients treated with caplacizumab were refractory to treatment compared to three patients treated with placebo p="0.057)." the analysis of the fourth key secondary endpoint showed a trend to faster normalisation of the organ damage markers lactate dehydrogenase cardiac troponin i and serum creatinine in patients treated with caplacizumab.>

Based on the topline data, the safety profile of caplacizumab is consistent with its mechanism of action and the Phase II TITAN study results. The number and nature of treatment-emergent adverse events (TEAEs) were similar between the treatment groups. Serious TEAEs were more common in the placebo group, driven by the percentage of patients experiencing a recurrence of aTTP. Consistent with the mechanism of action of caplacizumab, the percentage of subjects with any bleeding-related TEAE was higher in the caplacizumab treatment group than in the placebo treatment group (66.2% vs. 49.3%). Most bleeding-related TEAEs were mild or moderate in severity. There were three deaths in the placebo group and none in the caplacizumab group during the study drug treatment period. One patient in the caplacizumab group died in the follow-up period after completing the study drug treatment and this was assessed by the investigator not to be related to study drug.

Professor Marie Scully, leading TTP specialist from the University College Hospital in London and Investigator in the HERCULES study commented: "The results of this landmark trial constitute a complete game changer for patients with aTTP. They will revolutionise how we manage the acute phase of the disease, which is when patients are at highest risk for organ damage, recurrence and death.".

Caplacizumab is wholly-owned by Ablynx and this reported data will be used to support the registration process for caplacizumab in Europe and the USA.