Fedratinib, the first selective JAK2 inhibitor approved for treatment of myelofibrosis - an option beyond ruxolitinib

Introduction Myelofibrosis, a life shortening clonal disorder, presents with a constellation of features: bone marrow fibrosis, abnormal blood counts, extramedullary hematopoiesis, splenomegaly, thrombohemorrhagic complications, and constitutional symptoms. Until recently Ruxolitinib, a JAK1 and 2 inhibitor, has been the only targeted therapy available for transplant-ineligible patients requiring treatment for splenomegaly and disease-related symptoms. However, most patients discontinue Ruxolitinib after 3-5 years, mostly due to loss of response. There has been an unmet need for this patient group. In August 2019, Fedratinib (INREBIC (R) capsules, Impact Biomedicines, Inc., a wholly owned subsidiary of Bristol Meyer Squibb), a JAK2 inhibitor, was approved by US FDA for treatment of myelofibrosis in both JAK inhibitor naive and pre-treated patients for the management of symptoms and splenomegaly. Areas covered Here, we discuss the development, evidence base to date for Fedratinib. Including early and late phase, and ongoing trials, safety issues, potential role and current position of Fedratinib in the treatment of myelofibrosis, as well as future direction of targeted therapy in myelofibrosis. Expert opinion Fedratinib presents a much needed option of treatment, particularly, for patients failing Ruxolitinib, with response rates that are quite similar. Nonetheless, there remain important questions including sequencing and options for combining therapy.

Automated summary

This article discusses the development and evidence base of Fedratinib, a new drug for the treatment of myelofibrosis. It addresses its efficacy, safety concerns, and future directions in targeted therapy for myelofibrosis. Fedratinib presents a much-needed treatment option, especially for patients who have failed Ruxolitinib.