FDA Grants Priority Review for Fedratinib in Myelofibrosis

Fedratinib May Represent New Option for Jakafi-Resistant Myelofibrosis

by Dr. C.H. Weaver M.D. updated 3/2019

Patients with myelofibrosis resistant or intolerant to Jakafi (ruxolitinib) may have an alternative treatment option with a novel JAK2-selective inhibitor fedratinib, according to the results of clinical study recently published in the medical journal Lancet.(1)

About Myelofibrosis

Myelofibrosis is a type of blood cancer known as a myeloproliferative neoplasm that is chronic and progressive in nature. It involves the abnormal development and function of bone marrow cells that produce blood cells and leads to the formation of scar tissue in the bone marrow. When the bone marrow becomes scarred it can’t make enough blood cells and this can cause anemia, enlargement of the spleen and liver, fatigue, and other problems.

Myelofibrosis can result from a worsening of other bone marrow diseases, such as polycythemia vera and essential thrombocythemia or develop on its own – so called primary myelofibrosis.

Approved in 2011, Jakafi is currently the only drug that has been approved specifically for myelofibrosis. Known as a JAK inhibitor, it is a targeted therapy that improves survival and can help to relieve the signs and symptoms of myelofibrosis, such as enlargement of the spleen, night sweats, itching, and bone or muscle pain.2

Janus-associated kinases 1 and 2 mediate the signaling of cytokines and growth factors important for blood production and immune function. The JAK1/JAK2 cellular pathway has demonstrated activity involved in the progression of Myelofibrosis. Medications such as Jakafi and fedratinib block the activity of the JAK1/JAK2 pathway which reduces the negative effects caused by its activity and are referred to as JAK inhibitors. Some patients treated with Jakafi do not achieve a reduction in spleen volume and about one-half will discontinue treatment after 3 to 5 years. Fedratinib inhibits the JAK 2 kinase and may represent a treatment option for these patients.

In the current study doctors investigated the effectiveness and safety of fedratinib in 97 patients with either primary myelofibrosis or those developing myelofibrosis after polycythemia, or essential thrombocytopenia who were either intolerant or resistant to treatment with Jakafi.

Overall fedratinib was effective in reducing splenomegaly and symptom burden in patients who had previously discontinued Jakafi therapy due to either intolerance or resistance. By 6 months, 55% of all patients achieved a reduction in spleen size spleen and 53% of the Jakafi resistant and 63% of the Jakafi intolerant patients ultimately achieved a response to treatment. About one-quarter (26%) of patients achieved a 50% or greater reduction in total symptom score compared with baseline.

The U.S. Food and Drug Administration (FDA) has granted a Priority Review to fedratinib. Fedratinib may soon represent an effective treatment option for selected individuals with myelofibrosis.


  1. [http://www.thelancet.com/pdfs/journals/lanhae/PIIS2352-3026(17)30088-1.pdf](https://www.thelancet.com/pdfs/journals/lanhae/PIIS2352-3026(17%2930088-1.pdf)

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