Eltrombopag

Medical uses

Eltrombopag is indicated for the treatment of thrombocytopenia in people with persistent or chronic immune thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy; for the treatment of thrombocytopenia in people with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy; in combination with standard immunosuppressive therapy for the first-line treatment of people with severe aplastic anemia; and for the treatment of people with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.

Development

In preclinical studies, the compound was shown to interact selectively with the thrombopoietin receptor, leading to activation of the JAK-STAT signaling pathway and increased proliferation and differentiation of megakaryocytes. Animal studies confirmed that it increased platelet counts. In 73 healthy volunteers, higher doses of eltrombopag caused larger increases in the number of circulating platelets without tolerability problems.

Clinical trials

Eltrombopag has been shown to be effective in two major clinical syndromes: idiopathic thrombocytopenic purpura (ITP) and cirrhosis due to hepatitis C (in which low platelet counts may be a contraindication for interferon treatment).

After six weeks of therapy in a phase III trial, eltrombopag 50 mg/day was associated with a significantly higher response rate than placebo in adult patients with chronic idiopathic thrombocytopenic purpura (ITP).

History

Eltrombopag received breakthrough therapy designation from the US Food and Drug Administration (FDA) in February 2014, for people with aplastic anemia for which immunosuppression has not been successful. In 2017, the NIH made Eltrombopag a standard of care in aplastic anemia.

Society and culture

Legal status

In October 2024, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Eltrombopag Viatris, intended for the treatment of people with primary immune thrombocytopenia (ITP) and thrombocytopenia associated with chronic hepatitis C. The applicant for this medicinal product is Viatris Limited. Eltrombopag Viatris was authorized in December 2024.

Research

It has been shown to produce a trilineage hematopoiesis in some people with aplastic anemia, resulting in increased platelet counts, along with red and white blood cell counts. Eltrombopag has been shown to target ELAVL1/HuR-RNA interactions affecting gene expression, iron metabolism, and glycoprotein hormones, alpha polypeptide (CGA) levels. The transcription factor EB (TFEB) has been detected as an Eltrombopag target in starvation-induced conditions.

References

References

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19. (March 2014). "Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug". Blood.
20. (January 2025). "Effects of genetic ablation and pharmacological inhibition of HuR on gene expression, iron metabolism, and hormone levels". BMC Biology.
21. (February 2023). "A small-molecule drug inhibits autophagy gene expression through the central regulator TFEB". Proceedings of the National Academy of Sciences of the United States of America.