OREANDA-NEWS. Ablynx today announced that the first patient with acquired thrombotic thrombocytopenic purpura (aTTP), who completed the Phase III HERCULES study of caplacizumab, has rolled-over into a three-year follow-up study.

Acquired TTP is an acute, ultra-rare, life-threatening blood clotting disorder in which uncontrolled platelet aggregation and microclot formation cause small blood vessel occlusions throughout the body, resulting in thrombotic complications and widespread organ damage. Despite the current standard-of-care treatment of daily plasma exchange (PEX) and immunosuppression, episodes of aTTP are still associated with a mortality rate of up to 20%, with most deaths occurring within 30 days of diagnosis. Furthermore, patients are at risk of acute thromboembolic complications (e.g. stroke, venous thrombosis and myocardial infarction) and of recurrence of disease. In addition, some patients are refractory to therapy, which is associated with a very poor prognosis for survival of an acute episode of aTTP. Long term, patients are at increased risk of hypertension, major depression, and premature death.

The objectives of this study are to evaluate the long-term safety and efficacy of caplacizumab and repeated use of caplacizumab, and to characterise the long term impact of aTTP. Patients will attend twice yearly visits and undergo a number of clinical, cognitive, and quality of life assessments. Safety laboratory parameters, immunogenicity of repeated treatment with caplacizumab and disease-related markers will be evaluated.

Upon any recurrence of acquired TTP, standard-of-care treatment consisting of daily plasma exchange (PEX) and immunosuppression will be initiated together with open-label caplacizumab. Patients will receive an intravenous bolus injection of caplacizumab at the start of PEX treatment followed by daily subcutaneous injections for the duration of daily PEX and for 30 days thereafter. Treatment with caplacizumab may be extended in the case of persistent signs and symptoms of underlying disease (e.g. ADAMTS13 activity profile remains below 10%).

The study duration is anticipated to be approximately three years from the date the last patient rolls over from the HERCULES trial.

Dr Edwin Moses, CEO of Ablynx commented: "As pioneers in the treatment of acquired TTP, we are committed to making caplacizumab available for patients suffering from this severe disease for which there is currently no specifically approved drug available. The safety and efficacy of caplacizumab has been demonstrated in the Phase II study and recruitment in the recently expanded Phase III study is proceeding well ahead of schedule. We are on track to file for conditional approval of caplacizumab in early 2017 in Europe and to communicate Phase III topline results before the end of 2017. In parallel, we have started to invest in our own commercial infrastructure and key expertise to support the anticipated launch of caplacizumab in Europe and North-America."

aTTP is an acute, ultra-rare, life-threatening, blood clotting disorder, affecting up to 11 per million people worldwide. It has a sudden onset caused by impaired activity of the ADAMTS13 enzyme (typically <10% of that in normal plasma), leaving ULvWF molecules uncleaved (vWF is an important protein involved in the blood clotting process). These ULvWF molecules spontaneously bind to blood platelets, resulting in severe thrombocytopenia (very low platelet count) and micro-clot formation in small blood vessels throughout the body, leading to thrombotic complications and widespread organ damage.

Up to 20% of patients die from an initial aTTP episode with most deaths occurring within 30 days of diagnosis. In addition to the acute risks of the disease, patients experiencing an episode of aTTP may suffer long-term consequences such as cognitive deficits, depression, and arterial hypertension, and are at risk for recurrence. The recurrence rate ranges from 10-84% and typically occur within 1-2 years, but recurrences have been reported up to 30 years after the initial episode.

Ablynx is a biopharmaceutical company engaged in the development of Nanobodies®, proprietary therapeutic proteins based on single-domain antibody fragments, which combine the advantages of conventional antibody drugs with some of the features of small-molecule drugs. Ablynx is dedicated to creating new medicines which will make a real difference to society. Today, the Company has more than 45 proprietary and partnered programmes in development in various therapeutic areas including inflammation, haematology, immuno-oncology, oncology and respiratory disease. The Company has collaborations with multiple pharmaceutical companies including AbbVie, Boehringer Ingelheim, Eddingpharm, Genzyme, Merck & Co., Inc., Merck KGaA, Novartis, Novo Nordisk and Taisho Pharmaceuticals. The Company is headquartered in Ghent, Belgium.