The FDA ( Food and Drug Administration ) has approved Inrebic ( Fedratinib ) 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, a double-blind, randomized, placebo-controlled trial in 289 patients with intermediate-2 or high-risk myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis with splenomegaly.
Patients were randomized to receive either INREBIC 500 mg ( n=97 ), 400 mg ( n=96 ) or placebo ( n=96 ) once daily for at least 6 cycles.
The primary efficacy outcome was the proportion of patients achieving greater than or equal to 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% ) have achieved a greater than or equal to 35% reduction in spleen volume, compared with 1 of 96 patients who received placebo ( p less than 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 greater than or equal to 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 health care professionals and patients about the risk of serious and fatal encephalopathy, including Wernicke’s encephalopathy.
Health care 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 ( greater than or equal to 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.
It is necessary to reduce dose for patients taking strong CYP3A inhibitors or for patients with severe renal impairment. ( Xagena )
Source: FDA, 2019