Fedratinib is effective to reduce splenomegaly and symptom burden in patients with myelofibrosis (MF), but therapy was associated with toxic effects in some patients, according to a recent study published online this week in the journalJAMA Oncology.

In the double-blind, international, placebo-controlled, phase 3 trial, patients were 18 years of age or older, hadintermediate-2 or high-risk primary MF, and had primary (post–polycythemia vera) or secondary (post–essential thrombocythemia) MF.

The researchers randomly assigned 289 patients to 400 mg fedratinib, 500 mg fedratinib, or placebo, for at least six 28-day cycles.

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The primary endpoint was spleen response, greater than or equal to 35% reduction in spleen volume from baseline. The secondary endpoint was symptom response, greater than or equal to 50% reduction in total symptom score.

Results showed that spleen response was better in the fedratinib 400-mg group with 36% (95% CI: 27, 46) and fedratinib 500-mg group with 40% (95% CI: 30, 50), compared with placebo group with 1% (95% CI: 0, 3) (P<0.001).

Likewise, symptom response was better in fedratinib 400-mg group with 36% (95% CI: 26, 46) and fedratinib 500-mg group with 34% (95% CI: 24, 44), compared with placebo group with 7% (95% CI: 2, 13) (P<0.001). 

Despite having these favorable clinical outcomes, 4 cases of encephalopathy were found in fedratinib 500-mg group.

RELATED: Pacritinib Reduces Spleen Volume in Patients with Myelofibrosis

Common adverse events such as anemia, gastrointestinal symptoms, increased levels of liver transaminases, serum creatinine, and pancreatic enzymes were found in fedratinib groups.

The findings suggest that fedratinib has activity against primary and secondary MF but serious adverse events such as encephalopathy of unknown mechanism were present. Therefore, clinical development of fedratinib has been discontinued.


  1. Pardanani A, Harrison C, Cortes JE, et al. Safety and efficacy of fedratinib in patients with primary or secondary myelofibrosis. JAMA Oncol. 2015. [Epub ahead of print]. doi: 10.1001/jamaoncol.2015.1590.