FDA Approves Fedratinib for Myelofibrosis
On August 16, 2019, the U.S. Food and Drug Administration (FDA) approved fedratinib (Inrebic®) for adults with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF).
Efficacy was investigated in JAKARTA (NCT01437787), a double-blind, randomized, placebo-controlled trial in 289 patients with intermediate-2 or high-risk MF, post-polycythemia vera MF, or post-essential thrombocythemia MF with splenomegaly. Patients were randomized to receive either fedratinib 500 mg (n = 97), 400 mg (n = 96) or placebo (n = 96) once daily for at least six cycles.
The primary efficacy outcome was the proportion of patients achieving at least a 35% reduction from baseline in spleen volume at the end of cycle six measured by MRI or CT with a follow-up scan four weeks later. Of the 96 patients treated with the recommended dose (400 mg) of fedratinib, 35 (37%) achieved at least a 35% reduction in spleen volume, compared with 1 of 96 patients who received placebo (p < 0.0001). The median duration of spleen response was 18.2 months for the fedratinib 400 mg group. In addition, 40% of patients who received 400 mg experienced at least a 50% reduction in myelofibrosis-related symptoms, whereas only 9% of patients receiving placebo experienced a decline in those symptoms.
The prescribing information for fedratinib includes a boxed warning to advise healthcare professionals and patients about the risk of serious and fatal encephalopathy, including Wernicke encephalopathy. Assess thiamine levels in all patients prior to starting fedratinib, periodically during treatment, and as clinically indicated. If encephalopathy is suspected, fedratinib should be immediately discontinued and parenteral thiamine initiated.
The most common adverse reactions (≥ 20%) in patients who received fedratinib were diarrhea, nausea, anemia, and vomiting.
The recommended fedratinib dose is 400 mg orally once daily with or without food for patients with a baseline platelet count of greater than or equal to 50 x 109/L. Reduce dose for patients taking strong CYP3A inhibitors or for patients with severe renal impairment.
Fedratinib was granted priority review and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
In collaboration with the FDA and as a service to our members, ONS provides updates on recent FDA approvals and other important FDA actions (e.g., updated safety information, new prescribing information) pertaining to therapies for patients with cancer. This allows the agency to inform oncologists and professionals in oncology-related fields in a timely manner. Included in the FDA updates is a link to the product label or to other sites for additional relevant clinical information. In supplying this information, ONS does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described.