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New England Journal of Medicine Publishes Ablynx’s Phase II TITAN Study

New England Journal of Medicine Publishes Ablynx’s Phase II TITAN Study

  • Proof-of-concept in the Phase II TITAN study was achieved with significant reductions in time to platelet count normalisation and recurrences while on treatment with caplacizumab
  • Based on these results, Ablynx is on track to file for conditional approval of caplacizumab in Europe in the first half of 2017
  • A confirmatory international Phase III study in patients with acquired TTP is ongoing and will be used to support a BLA submission in 2018 in the USA
  • Ablynx intends to lead the commercialisation of caplacizumab in Europe and the USA

Ghent, Belgium, 11 February 2016 - Ablynx [Euronext Brussels: ABLX; OTC: ABYLY] today announced that the results of the Company’s worldwide Phase II TITAN study1 with caplacizumab for patients with acquired thrombotic thrombocytopenic purpura (aTTP) have been published in today’s issue of 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 II 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 journal2 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 III study before the end of 2017. We look forward to making caplacizumab available for patients with this devastating disease.”

About caplacizumab and the TITAN study results
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 II TITAN study in 75 patients with aTTP:

  • As indicated by a nearly 40% reduction in median time to platelet count normalisation (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.

More information on caplacizumab, including the NEJM paper, can be found on Ablynx’s website.

1Top line data from the TITAN study were communicated in June 2014 and were subsequently presented at ASH 2014 and ISTH 2015 (results from post hoc analysis and ADAMTS13 activity to guide treatment duration)
2The most recent (2014) impact factor for NEJM is 55.873, the highest among general medical journals

About aTTP
aTTP 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 (typically <10% of that in normal plasma), 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 body3.

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%4, typically occurring within 2 weeks after initial diagnosis. Moreover, about 36% of patients have recurrences5 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.

Phase II TITAN clinical study
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 II TITAN clinical trial which was a single-blinded, randomised, placebo-controlled study. In total, 75 patients were randomised 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 centres worldwide, with investigators from countries including Italy, England, Switzerland, the USA and Austria.

Phase III HERCULES clinical study
The worldwide Phase III HERCULES study is a multinational, double-blind, placebo-controlled study evaluating the efficacy and safety of caplacizumab, in conjunction with the standard of care, in patients with aTTP. The study is expected to enrol 92 patients at clinical sites across 17 countries. The primary endpoint is time to platelet count normalisation. Other clinically relevant endpoints include: the prevention of recurrence of the presenting TTP episode after stopping daily PEX; the effect on biomarkers of organ damage; severe morbidity associated with tissue ischemia and; mortality. Recruitment for this study is expected to be completed by the end of 2017, followed by an anticipated BLA filing in the USA in 2018.

About Ablynx
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 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. More information can be found on

3Veyradier, NEJM 2016: “von Willebrand Factor – A new target for TTP treatment?”
4Allford et al, BJH 2003, Kremer Hovinga, Blood 2010; Benhamou, Haematologica 2012
5George et al, EJB 2008

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