On August 16, 2019, the FDA approved fedratinib (Inrebic; Celgene) for the treatment of patients with intermediate-2 or high-risk primary or secondary (post–polycythemia vera or post–essential thrombocythemia) myelofibrosis.
“Prior to [this approval], there was one FDA-approved drug to treat patients with myelofibrosis, a rare bone marrow disorder. Our approval provides another option for patients,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence, and Acting Director of the Office of Hematology and Oncology Products, FDA’s Center for Drug Evaluation and Research.
This approval was based on the phase 3, multicenter, randomized, double-blind, placebo-controlled JAKARTA clinical trial of 289 patients with intermediate-2 or high-risk myelofibrosis, post–polycythemia vera myelofibrosis, or post–essential thrombocythemia myelofibrosis with splenomegaly.
Patients were randomized to fedratinib 500 mg (N = 97), fedratinib 400 mg (N = 96), or placebo (N = 96) once daily for ≥6 cycles. The primary end point of the trial was spleen response rate, defined as the proportion of patients achieving ≥35% reduction from baseline in spleen volume at the end of cycle 6, as measured by magnetic resonance imaging or computerized tomography with a follow-up scan 4 weeks later. Additional end points included symptom response rate, defined as the proportion of patients with a ≥50% reduction in Total Symptom Score when assessed from baseline to the end of cycle 6 as measured by the modified Myelofibrosis Symptoms Assessment Form v2.0 diary (ie, night sweats, itching, abdominal discomfort, early satiety, pain under ribs on left side, bone or muscle pain).
Results showed a ≥35% reduction in spleen volume when assessed from baseline to the end of cycle 6 (week 24), with a 4-week follow-up scan, in 37% of patients treated with fedratinib 400 mg versus 1% of patients who received placebo (P <.0001). In addition, 40% of patients treated with fedratinib 400 mg had a ≥50% reduction in myelofibrosis-related symptoms, versus 9% of patients who received placebo (P <.0001).
The most common adverse reactions (≥20%) in patients treated with fedratinib were diarrhea, nausea, anemia, and vomiting. Serious adverse reactions occurred in 21% of patients treated with fedratinib 400 mg once daily, with the most common (≥2%) being cardiac failure (5%) and anemia (2%).
Fedratinib has a boxed warning for serious and fatal encephalopathy, including Wernicke’s encephalopathy, a neurologic disorder induced by thiamine (vitamin B1) deficiency. Healthcare professionals are advised to assess thiamine levels in all patients before initiating fedratinib therapy, periodically during treatment, and as clinically indicated. If encephalopathy is suspected, fedratinib should be immediately discontinued and parenteral thiamine initiated.