<p>Caplacizumab as an emerging treatment option for acquired thrombotic thrombocytopenic purpura</p>

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a rare disease with a mortality rate of over 90% if left untreated. Therapeutic plasma exchange (PEX) is the mainstay of treatment of acquired TTP (aTTP), and with the introduction of PEX, the mortality rate declined dramatically below 20%. Although PEX together with corticosteroids are the backbone of the upfront management of patients with aTTP with successful outcomes, patients may remain refractory and/or relapse following an initial response to this treatment. There are some therapeutic options, which can be used among these patients, helping in improving outcomes of aTTP. Caplacizumab (formerly ALX-0081 or ALX-0681) is a humanized single-variable domain immunoglobulin that recognizes the human von Willebrand factor (vWF) A1 domain and inhibits the vWF–platelet glycoprotein 1b-alpha (GP1b-α) interaction. The drug was first developed for the prevention of thrombosis in high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention; however, drug development for this indication has been discontinued. Recently, caplacizumab received its first approval following Phase II TITAN and Phase III HERCULES trials in the European Union (EU) for the treatment of acute episode of aTTP in adult patients, in addition to PEX and immunosuppression. This review focuses on the use of caplacizumab as an emerging treatment option in patients with aTTP.

Humanized Single Domain Antibodies Neutralize SARS-CoV-2 by Targeting Spike Receptor Binding Domain

“…FDA approved the first sdAb-based medicine for adults with acquired thrombotic thrombocytopenic purpura in 2019 17–20 . Considering the cost and potential risks of full human antibody in some viral diseases, such as dengue virus infection, sdAb fragments are a novel category of therapeutic molecules and can be readily reconstructed in a tandemly linked way to increase their blood residential time, biological activity, and eliminate underlying concerns about antibody-dependent enhancement (ADE) of viral infection 21 .…”

Longitudinal assessments of plasma ADAMTS13 biomarkers predict recurrence of immune thrombotic thrombocytopenic purpura

“…For instance, IgG 4 levels, but not other IgG subtypes, are higher in those who relapsed than in those who did not. 38,39 With the rapid expansion of high-cost, but perhaps efficacious, pharmacological therapies such as rituximab 40,41 and caplacizumab, 17,18,42,43 in addition to standard of care (eg, TPE and corticosteroids), a reliable biomarker that predicts the likelihood of exacerbation and/or recurrence may help guide the timing, dosage, and duration of usage of such expensive therapeutic modalities, particularly in low-resource regions. Rituximab targets CD20 on B-lymphocytes, resulting in elimination of clonal B cells that may produce inhibitory antibodies toward ADAMTS13.…”

G Protein–Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action

“…In comparison with conventional antibodies, nanobodies are associated with several advantages, such as better solubility and tissue penetration, low immunogenicity, and high physical stability, and they can be easily produced in prokaryotic or eukaryotic host organisms (Harmsen and De Haard, 2007;Joost and Kolkman, 2010;Klarenbeek et al, 2012). Currently, only one nanobody, caplacizumab, is on the market (Elverdi and Eskazan, 2019). Caplacizumab targets the von Willebrand factor (a clotting protein), and it was approved by FDA in 2019 for the treatment of acquired thrombotic thrombocytopenic turpura and thrombosis Reichert, 2018, 2019).…”