FDA Approves Fedratinib for Myelofibrosis

Evidence for efficacy is based on results from the JAKARTA study

On 16 August 2019, the US Food and Drug Administration (FDA) approved fedratinib (INREBIC, Impact Biomedicines, Inc.) for adults with intermediate-2 or high-risk primary or secondary (post-polycythaemia vera or post-essential thrombocythemia) myelofibrosis (MF).

Efficacy was investigated in JAKARTA (NCT01437787), a double-blind, randomised, placebo-controlled trial in 289 patients with intermediate-2 or high-risk MF, post-polycythaemia vera MF, or post-essential thrombocythemia MF with splenomegaly. Patients were randomised to receive either INREBIC 500 mg (97 patients), 400 mg (96 patients) or placebo (96 patients) once daily for at least 6 cycles.

The primary efficacy outcome was the proportion of patients achieving ≥35% reduction from baseline in spleen volume at the end of cycle 6 measured by MRI or CT with a follow-up scan 4 weeks later.

Of the 96 patients treated with the recommended dose (400 mg) of fedratinib, 35 (37%) achieved 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 a ≥50% reduction in myelofibrosis-related symptoms, whereas only 9% of patients receiving placebo experienced a decline in these 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’s encephalopathy. Healthcare professionals are advised to 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 diarrhoea, nausea, anaemia, 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 50x109/L. Reduce dose for patients taking strong CYP3A inhibitors or for patients with severe renal impairment.

Full prescribing information for INREBIC is available here.

Fedratinib was granted priority review and orphan drug designation.

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.