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