Rare Daily Staff

Ablynx reported positive topline results from a late-stage study of caplacizumab, its experimental therapy to treat acquired thrombotic thrombocytopenic purpura, or aTTP, a rare, acute, life-threatening, autoimmune blood clotting disorder.

The company said the study showed that treatment with caplacizumab in addition to standard-of-care resulted in a statistically significant reduction in time to platelet count response, 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 results of this landmark trial constitute a complete game changer for patients with aTTP,” said Marie Scully, a leading TTP specialist from the University College Hospital in London and investigator in the study. “They will revolutionize how we manage the acute phase of the disease, which is when patients are at highest risk for organ damage, recurrence, and death.”

Caplacizumab blocks the interaction of critical protein that controls bleeding with platelets. It has an immediate effect on platelet aggregation and the ensuing formation and accumulation of the micro-clots that cause the severe thrombocytopenia, tissue ischemia, and organ dysfunction in aTTP.

The late-stage study also met the first two key secondary endpoints. Treatment with caplacizumab resulted in a 74 percent reduction in the percentage of patients with aTTP-related death, recurrence of aTTP, or at least one major thromboembolic event during study drug treatment, 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 percent lower in the caplacizumab arm compared to the placebo arm. The company said that was a demonstration of 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 normalization of the organ damage markers (lactate dehydrogenase, cardiac troponin I and serum creatinine) in patients treated with caplacizumab.

The number and nature of treatment-emergent adverse events were similar between the treatment groups. Serious treatment-emergent adverse events 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 percent vs. 49.3 percent). Most bleeding-related treatment-emergent adverse events 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.

October 2, 2017

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