Caplacizumab – wholly-owned anti-vWF Nanobody to treat acquired Thrombotic Thrombocytopenic Purpura (aTTP)
- Caplacizumab has the potential to become an important new component in the standard of care for acquired thrombotic thrombocytopenic purpura (aTTP)
- Caplacizumab received Orphan Drug status in 2009 (FDA and EMA)
- Phase II clinical proof-of-concept data communicated in June 2014 demonstrated that caplacizumab protects the patients in the acute phase of the disease and rapidly inhibits platelet aggregation, micro-clot formation and small blood vessel occlusion, thereby having the potential to prevent further organ damage. The data also showed that caplacizumab reduced the duration of plasma exchange treatment and led to an important reduction in recurrences of the disease during treatment.
- Filing expected in H1 2017 for conditional approval in Europe based on Phase II results
- Phase III study started in Q3 2015 to support BLA submission in the USA
- Ablynx committed to lead commercialisation of caplacizumab in the USA and Europe
- Ablynx initiated a three-year Phase III follow-up study in October 2016
Video: TITAN Study - Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura
Access the TITAN manuscript in Medical Journal – published 11 February 2016
Caplacizumab and aTTP media backgrounder
Unmet medical need in TTP
Acquired TTP is an ultra-rare, acute, life-threatening blood clotting disorder that leads to extensive micro-clot formation in the small blood vessels throughout the body and tissue ischaemia and damage to vital organs, including the heart, brain and kidneys. Mortality is high at 10-20%, with vast majority within 2 weeks post diagnosis, and about 36% of patients suffer from recurrences  after initial treatment with the current standard-of-care, which consists of plasma exchange (PE) plus immune-suppressive treatment. In addition, the organ damage caused by a TTP episode may result in poor longer term outcomes.
There remains a high unmet medical need to immediately inhibit the formation of microvascular thrombi, thereby reducing the risk of further organ damage. Maintenance of this platelet-protective effect is required until the underlying auto-immune activity has been resolved. Caplacizumab is being developed to address this unmet need and its clinical effect has been demonstrated in the Phase II TITAN study.
von Willebrand factor
von Willebrand factor (vWF) is a blood glycoprotein involved in haemostasis, a complex process that controls bleeding, and its primary function is to bind to other proteins, including glycoprotein Ib in the initiation of platelet adhesion.
What is the biological basis of TTP?
TTP exists in two forms: a congenital and an acquired form, with the latter accounting for >90% of the patients. The condition is characterised by severe thrombocytopenia (low blood platelet count), haemolytic anaemia (abnormal break down of red blood cells) and signs and symptoms of tissue ischemia (insufficient blood supply to organs), including stroke or myocardial infarctions. The ischemic damage may result in both acute complications as well as poor longer term outcomes. In the majority of patients, it is an autoimmune condition where auto-antibodies are generated to the enzyme ADAMTS13, which is responsible for ultra large vWF (ULvWF) cleavage. As a result of impaired ADAMTS13 activity (typically <10% of that in normal plasma), these ULvWF molecules spontaneously bind to platelets, resulting in ULvWF mediated platelet string formation in the small blood vessels.
Caplacizumab mode of action
Caplacizumab is a highly potent and selective bivalent anti-vWF Nanobody that received Orphan Drug Designation in the US and EU in 2009. It could be the first drug specifically approved for the treatment of acquired TTP.
Caplacizumab inhibits the interaction between vWF and platelets by targeting the A1 domain of vWF and thus has the potential to immediately block the ULvWF mediated platelet interactions and the formation of the string-like clots in the blood of patients with acquired TTP.
 George et al, 2008
 Scully et al, Br J Haematology 2012
Related presentations, abstracts and posters
Presentation: Caplacizumab may have the potential to reduce morbidity and mortality associated with acquired TTP: additional data from post-hoc analyses of the Phase II TITAN study of caplacizumab (presented at the first European Congress on Thrombosis and Haemostasis on 29 September 2016 in The Hague, The Netherlands)
Poster: Impact of caplacizumab treatment on mortality and major thromboembolic events in acquired TTP: Phase II TITAN study results (presented at the 21st European Hemathology Association Congress on 9 June 2016 in Copenhagen, Denmark)
Presentation: The predictive value of ADAMTS13 activity for treatment monitoring of patients with acquired TTP; data from the Phase II TITAN trial with caplacizumab (presented at the 2015 Annual Meeting of the ISTH on 24 June 2015 in Toronto, Canada)
Presentation: Additional data from the TITAN trial with the anti-vWF Nanobody, caplacizumab, in the treatment of acquired TTP (presented at the 2015 Annual Meeting of the ISTH on 24 June 2015 in Toronto, Canada)
Presentation of results of TITAN Phase II study with caplacizumab at ASH 2014
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pdf version of the presentation
Ablynx’s anti-vWF Nanobody, caplacizumab, achieved clinical proof-of-concept in Phase II study
pdf version of the presentation