Major Research Findings

Avatrombopag, an oral thrombopoietin receptor agonist, has been recently approved for treating thrombocytopenia in patients with chronic liver disease who need invasive procedures. This study evaluated the safety, tolerability, pharmacokinetic profile, and effect on platelet counts of avatrombopag in two double-blind, dose-escalating, placebo-controlled Phase 1 studies in healthy adults. The studies included a single-dose study (N=63) and a multiple-dose study (N=29). In the single-dose study, participants received avatrombopag (1, 3, 10, 20, 50, 75, or 100 mg) or placebo. In the multiple-dose study, participants received avatrombopag (3, 10, or 20 mg) or placebo daily for 14 days. The results showed that avatrombopag increased peak concentration and exposure proportionally to the dose. The half-life was 18-21 hours and was independent of the dose, supporting once-daily dosing. The effect on platelet counts depended on the dose, concentration, and treatment duration. Platelet counts began to increase 3-5 days after administration, with maximum changes of >370 × 10⁹/L over baseline with 20 mg daily after 13-16 days. These findings support further development of avatrombopag for the treatment of other thrombocytopenic conditions and provide important guidance for hematologists in the use of this new thrombopoietin receptor agonist.

Benefits and Risks

Benefit Summary

Avatrombopag is a safe and effective oral thrombopoietin receptor agonist for treating thrombocytopenia in patients with chronic liver disease who need invasive procedures. Avatrombopag increases platelet counts in a dose-dependent manner. Avatrombopag has a relatively long half-life, supporting once-daily dosing.

Risk Summary

Avatrombopag is generally safe, but like all medications, there are potential side effects. Common side effects of avatrombopag include headache, fatigue, indigestion, and abdominal pain. However, serious side effects such as thrombosis and liver function abnormalities can occur.

Study Comparison

Study Similarities

Both studies evaluated the safety, tolerability, pharmacokinetic profile, and effect on platelet counts of avatrombopag in healthy adults. Both studies found that avatrombopag increased peak concentration and exposure proportionally to the dose. The half-life was 18-21 hours and was independent of the dose, supporting once-daily dosing.

Study Differences

The two studies differed in the way avatrombopag was administered. One study was a single-dose study, while the other was a multiple-dose study. The doses of avatrombopag given in the two studies were also different.

Consistency and Discrepancies of Findings

The findings from the two Phase 1 studies were consistent in that avatrombopag was generally safe and increased platelet counts in a dose-dependent manner. However, there were a few discrepancies between the studies. For example, in one study, some participants did not show an increase in platelet counts after receiving avatrombopag, while in the other study, all participants showed an increase in platelet counts. These inconsistencies may be due to slight differences in the characteristics of the participants in the two studies or the study designs.

Real-World Application Considerations

Avatrombopag is approved for treating thrombocytopenia in patients with chronic liver disease who need invasive procedures. However, it may not be effective for all types of thrombocytopenia. It is important to consult with a healthcare provider before taking avatrombopag to discuss your medical history and current medications.

Limitations of Current Research

These Phase 1 studies were conducted in healthy adults, not patients with thrombocytopenia. Therefore, the findings may not be generalizable to patients with thrombocytopenia. The studies were also relatively short-term, so the long-term effects of avatrombopag are unknown. Additionally, the number of participants in these studies was limited, so the findings may not apply to all patients with thrombocytopenia.

Future Research Directions

Further research on the safety and efficacy of avatrombopag is needed. Long-term studies in patients with thrombocytopenia are particularly needed. Studies evaluating the efficacy of avatrombopag for other types of thrombocytopenia are also warranted. Furthermore, studies are needed to evaluate the interactions of avatrombopag with other medications.

Conclusion

Avatrombopag is a safe and effective oral thrombopoietin receptor agonist for treating thrombocytopenia in patients with chronic liver disease who need invasive procedures. However, further research is needed to confirm its safety and efficacy in a larger population, including patients with other types of thrombocytopenia. It is important to consult with a healthcare provider before taking avatrombopag to discuss your medical history and current medications.