The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.
Proposed Mechanism of Action
Fedratinib is an oral small molecule kinase inhibitor with higher selectivity for JAK2 over other JAK family members, including JAK1, JAK3 and tyrosine kinase 2.1-3 Myelofibrosis is a life-threatening myeloproliferative neoplasm (MNP) that occurs due to the proliferation of mutant hematopoietic stem and progenitor cells and can be caused by alterations in the JAK/STAT pathway.4,5 Approximately 60–65% of patients with primary myelofibrosis have a mutation in JAK2, typically JAK2V617F.5 An additional 20-30% of patients with primary myelofibrosis have abnormalities in markers mutant Calreticulin or the thrombopoietin receptor, also known as the myeloproliferative leukemia protein (MPL), which also signal through the JAK2/STAT pathway.5 Preclinical studies have suggested that fedratinib may inhibit both mutant and wild-type JAK2, thus blocking abnormal hyperactive JAK/STAT signaling and inhibiting proliferation in hematopoietic stem cells with or without mutations in JAK2.2,6,7
Fedratinib Proposed Mechanism of Action
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fedratinib by Disease State
fedratinib in Myelofibrosis
View Trials Investigating fedratinib in Myelofibrosis
View Rationale for Clinical Development
Rationale for Clinical Development
Preclinical studies using mouse models of JAK2V617F-driven myeloproliferative disease have suggested that fedratinib blocked phosphorylation of STAT 3/5 and improved survival, white blood cell counts, hematocrit, splenomegaly, and fibrosis, supporting the clinical development of fedratinib in myelofibrosis.1