NEJM publishes Ablyns’s Phase 2 TITAN study of caplacizumab in patients with acquired TTP

Proof-of- concept was achieved with significant reductions in time to platelet count normalization and recurrences while on treatment with caplacizumab

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GHENT/ZWIJNAARDE, Belgium—Ablynx recently announced that the results of the company's worldwide Phase 2 TITAN study] with caplacizumab for patients with acquired thrombotic thrombocytopenic purpura (aTTP) have been published in the New England Journal of Medicine (NEJM).
"Caplacizumab has the potential to become an important new component in the standard of care for patients with acquired TTP," said Professor Flora Peyvandi, principal investigator for the TITAN study at IRCCS Maggiore Hospital Foundation, University of Milan, Italy, and lead author of the NEJM paper. "The results from the Phase 2 TITAN study showed that caplacizumab acts quickly to control the critical acute phase of the disease and protects patients until immunosuppressive treatments take effect." 
Dr. Robert K. Zeldin, chief medical officer of Ablynx, commented: "The publication of the TITAN data in this high-impact clinical journal is a further validation of the potential of caplacizumab in the treatment of acquired TTP. This publication is the culmination of over a decade of work by Ablynx and its external collaborators. We are on track to file for conditional approval of caplacizumab in Europe in 2017 and to complete enrolment of the confirmatory Phase 3 study before the end of 2017. We look forward to making caplacizumab available for patients with this devastating disease." 
Caplacizumab is a highly potent and selective bivalent anti-von Willebrand Factor (vWF) Nanobody that received Orphan Drug Designation in the USA and EU in 2009. Caplacizumab inhibits the interaction between ultra-large vWF and platelets by targeting the A1 domain of vWF. It thereby prevents platelet aggregation and the formation of micro-clots during the acute, critical phase of acquired TTP.
Caplacizumab's clinical effect was demonstrated in the Phase 2 TITAN study in 75 patients with aTTP.
As indicated by a nearly 40 percent reduction in median time to platelet count normalization (p = 0.005), treatment with caplacizumab reduced the use of daily plasma exchange (PEX) and prevented further consumption of platelets in microthrombi and small blood vessel occlusion.
As shown by the low number of recurrences requiring re-initiation of daily plasma exchange during treatment with caplacizumab (N=3) vs. placebo (N=11), these results will serve as the basis for filing for conditional approval in Europe in H1 2017. Caplacizumab could be the first drug specifically approved for the treatment of acquired TTP. 
TTP is an ultra-rare, acute, auto-immune blood clotting disorder, affecting up to 11 per million people worldwide. It has a sudden onset caused by impaired activity of the ADAMTS13 enzyme, leaving ultra-large vWF molecules un-cleaved (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. 
aTTP is associated with major morbidities in the brain (e.g., stroke), heart and kidney and impacts life expectancy and quality of life. Mortality is high at 10-20 percent, typically occurring within 2 weeks after initial diagnosis. Moreover, about 36 percent of patients have recurrences after treatment with the current standard of care, which consists of daily PEX and immune-suppressants, and these recurrences have the potential to cause further organ damage and poorer longer term outcomes. 
The NEJM paper, titled "Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura" (Peyvandi et al., NEJM 2016: published 11 February 2016), reported data from the worldwide Phase 2 TITAN clinical trial which was a single-blinded, randomized, placebo-controlled study. In total, 75 patients were randomized on a 1:1 basis to active drug or placebo, with all patients receiving the current standard of care. Those patients in the active drug treatment arm immediately received an intravenous bolus dose of 10 mg caplacizumab and then a 10 mg subcutaneous dose of the drug daily until 30 days had elapsed after the final plasma exchange. Patients in the control arm received placebo at the same time points.
The TITAN study was conducted at 56 study centers worldwide, with investigators from countries including Italy, England, Switzerland, the USA and Austria. 
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 approximately 40 proprietary and partnered programs in development in various therapeutic areas including inflammation, hematology, 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.

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