On August 16, 2019, the FDA approved fedratinib (Inrebic; Celgene/Impact Biomedicines), an oral kinase inhibitor, for adults with intermediate-2 or high-risk primary or secondary—post–polycythemia vera (PV) or post–essential thrombocythemia (ET)—myelofibrosis, a rare bone marrow disorder. The FDA granted fedratinib priority review and an orphan drug designation.
“Myelofibrosis can cause patients to suffer in many ways, including experiencing debilitating symptoms,” said Ruben Mesa, MD, FACP, Director, Mays Cancer Center, San Antonio M.D. Anderson Cancer Center. “There has not been a new treatment approved for this disease in nearly a decade.”
The FDA approved fedratinib based on the JAKARTA study, a phase 3, double-blind, randomized, placebo-controlled clinical trial of 289 patients with intermediate-2 or high-risk myelofibrosis, post-PV myelofibrosis, or post-ET myelofibrosis with splenomegaly. Patients were randomized to 400 mg or 500 mg of fedratinib or to placebo once daily for at least 6 cycles.
The primary outcome was the proportion of patients achieving ≥35% reduction from baseline in spleen volume after 6 cycles of treatment. Of the 96 patients who received 400 mg of fedratinib, 35 (37%) achieved a ≥35% reduction in spleen volume versus 1 of 96 patients who received placebo (P <.0001). The median duration of spleen response was 18.2 months with 400 mg of fedratinib. In addition, 40% of patients who received the 400-mg dose had a ≥50% reduction in myelofibrosis-related symptoms versus only 9% of patients receiving placebo.
The most common (≥20%) side effects were diarrhea, nausea, anemia, and vomiting. Fedratinib was approved with a boxed warning about the risk for serious and fatal encephalopathy, including Wernicke’s encephalopathy.