Oral anticoagulation with edoxaban

Summary

Edoxaban (the former DU176b) an orally available direct factor Xa inhibitor has been engineered from DX-9065a, which was one of the first parenteral Xa inhibitors. Edoxaban has a time to peak plasma concentrations of 1–2 hours and a half-life of approximately 10 hours after multiple doses. Edoxaban is the third new oral anticoagulant in the group of direct factor Xa inhibitors that has gained clinical approval for the prevention of venous thromboembolism after major orthopaedic surgery. Currently, edoxaban is assessed in late stage clinical development for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (ENGAGE AF-TIMI 48, NCT00781391) and for the treatment and prevention of venous thromboembolism in patients with acute deep vein thrombosis and/or pulmonary embolism (HOKUSAI VTE, NCT00986154).

Both clinical phase III trials represent the largest single clinical studies in their entity so far with an enrolment of 21 107 patients in ENGAGE AF-TIMI 48 and a planned enrolment of 7500 patients in HOKUSAI VTE.

The pharmacological properties of edoxaban will be discussed along with the current late stage clinical development focusing on the prevention of stroke and venous thromboembolism.

Zusammenfassung

Edoxaban (ehemals DU176b) ist ein oral verfügbarer direkter Faktor-Xa(FXa)-Inhibitor der von der Substanz DX-9065a, einem der ersten parenteralen FXa-Inhibitoren abgeleitet wurde. Edoxaban erreicht Plasmaspitzenspiegel nach 1–2 Stunden und hat eine Halbwertszeit von ca. 10 Stunden nach wiederholter Verabreichung. Edoxaban ist das dritte der neuen oralen Antikoagulanzien aus der Gruppe der direkten FXa-Inhibitoren, dass zur Prophylaxe venöser Thromboembolien nach großen orthopädischen Operationen zugelassen wurde. Zurzeit wird Edoxaban in Phase-III-Zulassungsstudien zur Prävention von Schlaganfall und systemischen Embolien bei Patienten mit nicht-valvulärem Vorhofflimmern (ENGAGE AF-TIMI 48, NCT00781391) sowie zur Behandlung und Prophylaxe venöser Thromboemolie bei Patienten mit akuter tiefer Beinvenenthrombose und/oder Lungenembolie (HOKUSAI VTE, NCT00986154) untersucht.

Beide Phase-III-Studien sind die bisher größten klinischen Studien in ihrer jeweiligen Indikation mit Einschluss von 21 107 Patienten in der ENGAGE-AF-TIMI-48-Studie und einem geplanten Einschluss von 7500 Patienten in der HOKUSAI-VTE-Studie.

Die pharmakologischen Eigenschaften von Edoxaban sowie die fortgeschrittene späte klinische Entwicklungsphase werden diskutiert mit Fokus auf Schlaganfallprävention und Prophylaxe venöser Thromboembolien.

Keywords

Edoxaban - oral anticoagulants - FXa inhibitor - thrombosis - atrial fibrillation - stroke - VTE - PE

Schlüsselwörter

Edoxaban - orale Antikoagulanzien - FXa-Inhibitor - Thrombose - Vorhofflimmern - Schlaganfall - VTE - PE

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