Caplacizumab: a change in the paradigm of thrombotic thrombocytopenic purpura treatment

ABSTRACT

Introduction: Immune thrombotic thrombocytopenic purpura (iTTP) is an immune-mediated deficiency in von Willebrand factor-cleaving protease ADAMTS13 allowing unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis. Caplacizumab, an anti-von Willebrand factor humanized, bivalent single-domain nanobody preventing its binding to the platelet has been investigated and approved for use in the treatment of iTTP.

Areas covered: The purpose of this article is to summarize the available clinical data on the efficacy and safety of caplacizumab in iTTP and to provide our opinion on the place of caplacizumab in current treatment regimens.

Expert opinion: Caplacizumab is a new drug with a complementary mechanism of action with respect to the standard available therapeutics. It demonstrated efficacy in clinical trials through a faster platelet count normalization and protection of patients from exacerbations and refractoriness. Caplacizumab is well tolerated with minor bleeds as the most important side effect. The efficacy of caplacizumab now needs to be assessed in real-life but definitely, this drug opens hope for a significant improvement in iTTP prognosis at the very early, critical step of the disease.

Trial registration: ClinicalTrials.gov identifier: NCT03922308.

Trial registration: ClinicalTrials.gov identifier: NCT02553317.

KEYWORDS:

• Caplacizumab
• thrombotic thrombocytopenic purpura
• ADAMTS13
• von Willebrand factor
• targeted therapy

Article Highlights

• Immune thrombotic thrombocytopenic purpura (iTTP) is still a life-threatening disease. 10 to 15% of patients receiving standard treatment still die, most of deaths occurring within the first days of diagnosis.

• Caplacizumab is a new drug with a complementary mechanism of action with respect to the standard available therapeutics.

• Caplacizumab is a humanized anti-von Willebrand factor (vWF) Nanobody® that inhibits the vWF-mediated platelet adhesion and prevents further microthrombi formation.

• Two clinical trials demonstrated the safety and efficacy of caplacizumab in association with standard of care in iTTP.

• Forthcoming studies will need to assess cost-effectiveness of such new therapeutic strategy and whether all iTTP patients need caplacizumab from diagnosis.

• Therapeutic plasma exchanges in combination with immunosuppression with corticosteroids and B-cell depletion with rituximab along with caplacizumab should become the standard of care to treat iTTP in the next future and help in decreasing early iTTP mortality and relapse.

• This box summarizes key points contained in the article.

Declaration of interest

A Veyradier is a member of the Advisory boards for Ablynx-Sanofi, Roche-Chugai, Shire-Takeda. Y Benhamou is a member of the advisory boards or financial sponsorship from Bayer, BMS-Pfizer, Leo Pharma, Roche Chugai, Ablynx, Alexion, Abbvie, Sanofi. P Coppo is a member of the advisory board for Alexion, Shire and Ablynx part of Sanofi-Genzyme. He has received funds from Ablynx, Alexion, Octapharma, and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.