What is the main difference between avatrombopag/sucoxin and haitrombopag?

Avatrombopag and Lusutrombopag are both thrombopoietin receptor agonists (TPO-RAs). Their main mechanism of action is to promote platelet production by activating TPO receptors. They are used to treat thrombocytopenia caused by chronic liver disease or other causes. However, there are still many significant differences between the two in terms of chemical structure, indications, dosage regulation, onset of action, side effects, metabolism, etc. During clinical use, appropriate drugs must be selected based on the patient's specific condition.

First of all, in terms of indications, avatrombopag was first approved for the treatment of thrombocytopenia in patients with chronic liver disease (CLD) before undergoing elective invasive procedures, and was subsequently approved for the treatment of chronic immune thrombocytopenia (ITP) . In contrast, the current main indication of Hetrombopag is limited to thrombocytopenia associated with chronic liver disease, and it has not been widely approved for thrombocytopenia due to other causes such as ITP. Avatrombopag has shown good efficacy in multiple ITP clinical trials and has gradually become one of the first-line targeted treatment options. This is also the key difference in the scope of clinical use between the two.

Avatrombopag has a more flexible dosage adjustment scheme in terms of dosage and onset of action. The recommended starting dose for the treatment of ITP is 20 mg per day, which can be adjusted according to the patient's platelet response; when used for CLD-related thrombocytopenia, 40 mg or 60 mg per day can be given based on the baseline platelet level for 5 consecutive days. Hatrombopag is usually recommended to be taken at a fixed dose of 3 mg once a day for 7 consecutive days. This dose regulation is slightly less rigid, especially when patients have greatly different responses to the drug, which is not conducive to personalized treatment.

Drug metabolism pathways are also worth noting. Avatrombopag is mainly metabolized by the liverCYP2C9 and CYP3A enzymes, and has certain interaction potential with other drugs, while heltrombopag is metabolized by CYP4A and has relatively few drug interactions. This means that in patients who take more concomitant medications, such as antiviral therapy or anti-cancer therapy, more attention needs to be paid to the risk of metabolic interference with avatrombopag. In terms of side effects, the overall safety of both drugs is good. Common adverse reactions include headache, fatigue, nausea, increased ALT, etc. However, avatrombopag has less risk of thrombosis reported in long-term use, so it has higher sustainability and tolerability in patients with chronic ITP.

In terms of economy and accessibility, the two drugs are developed and marketed by different companies around the world, and avatrombopag is developed by the United StatesIt was developed by Dova Company (now part of Sobi), and Hatrombopag was developed by Japan's Shionogi Pharmaceutical Company. Avatrombopag has been launched in many countries at home and abroad in recent years, and has gradually been included in the medical insurance catalog, increasing its clinical utilization rate. However, heltrombopag was launched in China slightly later and has a relatively small market share. It needs to be emphasized that the choice of drugs not only depends on the efficacy, but also takes into account multiple factors such as the patient's cause, complications, medication history, and price factors.

Reference materials:https://go.drugbank.com/drugs/DB11995