Caplacizumab: an anti-von Willebrand factor antibody for the treatment of thrombotic thrombocytopenic purpura.

The pharmacology, pharmacokinetics, efficacy, safety, dosing and administration, and place in therapy of caplacizumab, a novel antibody fragment that inhibits von Willebrand factor, for the treatment of acquired thrombotic thrombocytopenic purpura (TTP) are summarized. Caplacizumab is a humanized anti-von Willebrand factor monoclonal antibody fragment that inhibits the interaction between ultralarge von Willebrand factor multimers and platelets. Caplacizumab is indicated for use in combination with standard-of-care modalities such as plasma exchange and immunosuppressive therapy for the treatment of adults with acquired TTP. By inhibiting von Willebrand factor, caplacizumab offers a new approach to the management of TTP by preventing the development of potentially life-threatening microvascular thrombosis that can occur in the disease process. In a randomized, placebo-controlled phase 3 trial, patients with acquired TTP treated with caplacizumab had more rapid platelet level normalization than placebo users; caplacizumab use also resulted in lower rates of disease recurrence and TTP-related death. The most common adverse events associated with caplacizumab use are bleeding-related events. In a phase 3 trial, serious bleeding-related adverse events were reported in 8 patients (11%) in the caplacizumab group and 1 patient (1%) in the placebo group. Caplacizumab is administered as an 11-mg intravenous loading dose 15 minutes prior to plasma exchange, followed by administration of 11 mg subcutaneously daily after plasma exchange. Once-daily caplacizumab administration can be continued for 30 days after the last plasma exchange. The medication and supplies for administration are provided as a single-use kit; patients should be trained on proper reconstitution and self-administration technique prior to the use of caplacizumab in the ambulatory setting. Caplacizumab is a first-in-class von Willebrand factor inhibitor approved for the treatment of adults with acquired TTP.

Hollifield AL ，Arnall JR ，Moore DC 《-》

Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura.

Scully M ，Cataland SR ，Peyvandi F ，Coppo P ，Knöbl P ，Kremer Hovinga JA ，Metjian A ，de la Rubia J ，Pavenski K ，Callewaert F ，Biswas D ，De Winter H ，Zeldin RK ，HERCULES Investigators ... -  《-》

Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura.

Peyvandi F ，Scully M ，Kremer Hovinga JA ，Cataland S ，Knöbl P ，Wu H ，Artoni A ，Westwood JP ，Mansouri Taleghani M ，Jilma B ，Callewaert F ，Ulrichts H ，Duby C ，Tersago D ，TITAN Investigators ... -  《-》

Caplacizumab for relapsing thrombotic thrombocytopenic purpura.

Kaczmarek V ，Holle J ，Astudillo R ，Kempf C ，Bufler P ，Müller D ... -  《-》

Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura.

Essentials Acquired thrombotic thrombocytopenic purpura (aTTP) is linked with significant morbidity/mortality. Caplacizumab's effect on major thromboembolic (TE) events, exacerbations and death was studied. Fewer caplacizumab-treated patients had a major TE event, an exacerbation, or died versus placebo. Caplacizumab has the potential to reduce the acute morbidity and mortality associated with aTTP. Background Acquired thrombotic thrombocytopenic purpura (aTTP) is a life-threatening autoimmune thrombotic microangiopathy. In spite of treatment with plasma exchange and immunosuppression, patients remain at risk for thrombotic complications, exacerbations, and death. In the phase II TITAN study, treatment with caplacizumab, an anti-von Willebrand factor Nanobody® was shown to reduce the time to confirmed platelet count normalization and exacerbations during treatment. Objective The clinical benefit of caplacizumab was further investigated in a post hoc analysis of the incidence of major thromboembolic events and exacerbations during the study drug treatment period and thrombotic thrombocytopenic purpura-related death during the study. Methods The Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) for 'embolic and thrombotic events' was run to investigate the occurrence of major thromboembolic events and exacerbations in the safety population of the TITAN study, which consisted of 72 patients, of whom 35 received caplacizumab and 37 received placebo. Results Four events (one pulmonary embolism and three aTTP exacerbations) were reported in four patients in the caplacizumab group, and 20 such events were reported in 14 patients in the placebo group (two acute myocardial infarctions, one ischemic stroke, one hemorrhagic stroke, one pulmonary embolism, one deep vein thrombosis, one venous thrombosis, and 13 aTTP exacerbations). Two of the placebo-treated patients died from aTTP during the study. Conclusion In total, 11.4% of caplacizumab-treated patients and 43.2% of placebo-treated patients experienced one or more major thromboembolic events, experienced an exacerbation, or died. This analysis shows the potential for caplacizumab to reduce the risk of major thromboembolic morbidities and mortality associated with aTTP.

Peyvandi F ，Scully M ，Kremer Hovinga JA ，Knöbl P ，Cataland S ，De Beuf K ，Callewaert F ，De Winter H ，Zeldin RK ... -  《-》