Nanobody is Potentially First Targeted Therapy for TTP Interview with:
Dr. Filip Callewaert PhD
Senior Clinical Scientist
Clinical Development, Ablynx
Zwijnaarde, Belgium

Medical Research: What is the background for this study? What are the main findings?

Dr. Callewaert: Acquired thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening coagulation disorder, in which accumulation of ultra-large von Willebrand factor (ULvWF) multimers is implicated, leading to an increased risk of thrombus formation in small blood vessels due to excessive platelet aggregation. There are no approved pharmacological therapies for acquired TTP. Despite treatment with the current standard of care (plasma exchange and immunosuppressive therapy), mortality remains at 10-20% and there is significant neurological, cardiac, and renal morbidity.

Caplacizumab is a bivalent Nanobody that binds to the A1 domain of vWF thereby preventing vWF-mediated platelet aggregation. The clinical effects of caplacizumab were demonstrated in the phase II randomised, placebo-controlled TITAN study in 75 patients with acquired TTP. Compared to placebo, there was a nearly 40% reduction in median time to platelet count normalisation in the caplacizumab group (p = 0.005). Treatment with caplacizumab reduced the use of daily plasma exchange and prevented further consumption of platelets in microthrombi and small blood vessel occlusion. In addition, there were fewer recurrences of TTP requiring re-initiation of daily plasma exchange during treatment with caplacizumab (N=3) vs. placebo (N=11). The safety profile of caplacizumab was favorable, with a slightly higher tendency of mostly mild bleeding events. 

Medical Research: What should clinicians and patients take away from your report?

Dr. Callewaert: Caplacizumab is potentially the first targeted therapy for acquired TTP. Caplacizumab acts quickly to control the critical acute microthrombotic phase of the disease, resulting in a faster normalization of platelet counts, and further protects patients against recurrences of TTP.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Callewaert: Future studies will focus on confirming the efficacy and safety of caplacizumab, and obtaining more data on the optimal treatment duration. In addition, long-term outcomes of TTP and the potential impact of caplacizumab treatment on these outcomes are potential areas of future research.   

Based on the results of the TITAN study, Ablynx is on track to file for conditional approval of caplacizumab in Europe in the first half of 2017.


Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura 

Flora Peyvandi, M.D., Ph.D., Marie Scully, M.D., Johanna A. Kremer Hovinga, M.D., Spero Cataland, M.D., Paul Knöbl, M.D., Haifeng Wu, M.D., Andrea Artoni, M.D., John-Paul Westwood, M.D., Magnus Mansouri Taleghani, M.D., Bernd Jilma, M.D., Filip Callewaert, Ph.D., Hans Ulrichts, Ph.D., Christian Duby, M.D., and Dominique Tersago, M.D. for the TITAN Investigators

N Engl J Med 2016; 374:511-522

February 11, 2016DOI: 10.1056/NEJMoa1505533

Dr. Filip Callewaert PhD (2016). Nanobody is Potentially First Targeted Therapy for TTP 

Last Updated on February 11, 2016 by Marie Benz MD FAAD