An evaluation of avatrombopag for the treatment of thrombocytopenia

ABSTRACT

Introduction: The thrombopoietin receptor agonists (TPO-RAs) are a class of drugs that have been FDA-approved for immune thrombocytopenia (ITP), periprocedural thrombocytopenia in patients with chronic liver disease (CLD), aplastic anemia, and thrombocytopenia associated with antiviral treatment of hepatitis C. Avatrombopag is a TPO-RA that is currently FDA-approved for ITP and periprocedural thrombocytopenia in patients with CLD and is currently undergoing evaluation for chemotherapy-induced thrombocytopenia (CIT) in an international phase III clinical trial.

Areas covered: This paper summarizes the chemistry, pharmacodynamics, and pharmacokinetics of avatrombopag. In addition, the authors review the efficacy and safety of avatrombopag, covering clinical trials in patients with ITP and in patients with CLD scheduled to undergo a procedure.

Expert opinion: Avatrombopag has demonstrated efficacy in patients with ITP. With its low side-effect burden, absence of hepatotoxicity, ease of use as an oral medication, and lack of food–drug interactions, avatrombopag is a favorable option for ITP, though there is a lack of long-term safety data. In periprocedural thrombocytopenia in patients with CLD, avatrombopag is comparable to lusutrombopag, another TPO-RA. Finally, the results of the study of avatrombopag in CIT are eagerly awaited, as there are no currently approved medications for this indication in the USA.

KEYWORDS:

• Avatrombopag maleate
• thrombocytopenia
• chronic liver disease
• AKR-501
• immune thrombocytopenia
• chemotherapy-induced thrombocytopenia
• thrombopoietin receptor agonist
• TPO-RA
• thrombopoietin

Article highlights

• Avatrombopag is an oral thrombopoietin receptor agonist currently approved for periprocedural thrombocytopenia in patients with chronic liver disease and chronic immune thrombocytopenia.

• Avatrombopag is effective in raising the platelet count in patients with immune thrombocytopenia and thrombocytopenia of chronic liver disease, with few side-effects. It lacks the signal for hepatotoxicity seen with eltrombopag and does not require the dietary restrictions around its administration required for eltrombopag.

• Additional studies are ongoing to evaluate the efficacy and safety of avatrombopag for the management of chemotherapy-induced thrombocytopenia.

Declaration of interest

H Al-Samkari has served as a consultant for Agios, Dova and Argenx and has received research funding from Agios, Dova and Amgen Inc. Furthermore, DJ Kuter has received research funding from Protalex, Bristol-Myers Squibb, Rigel, Bioverativ, Agios, Immunovant, Kezar, Syntimmune, Principia and Alnylam. He has also served as a consultant for ONO, Pfizer Inc, 3SBIos, Eisai, GlaxoSmithKline, Genzyme, Immunovant, Kezar, Shire, Amgen, Shionogi, Rigel, Syntimmune, MedImmune, Novartis, Alexion, Bioverativ, Argenx, Zafgen, Fujifilm, Principia, Kyowa Kirin, Takeda and the Platelet Disorders Support Association. 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 or other relationships to disclose.