FDA approves Inrebic to treat primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis

Celgene Corporation announced the FDA has approved Inrebic (fedratinib) for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis. The Inrebic development program consisted of multiple studies (including JAKARTA and JAKARTA2) in 608 patients who received more than one dose (ranging from 30 mg to 800 mg),1 of whom 459 had myelofibrosis, including 97 previously treated with ruxolitinib.

The JAKARTA study evaluated the efficacy and safety of once-daily oral doses of Inrebic compared with placebo in patients with intermediate-2 or high-risk, primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis who were previously untreated with a JAK inhibitor, had enlarged spleens (a condition known as splenomegaly), and had a platelet count of greater than 50 x 109/L (median baseline platelet count was 214 x 109/L; 16% <100 x 109/L and 84% greater than 100 x 109/L). In the JAKARTA study, spleen volume was reduced by 35% or greater, when assessed from baseline to the end of cycle 6 (week 24), with a 4-week follow-up scan, in 37% (35 of 96) of patients treated with Inrebic 400 mg versus 1% (1 of 96) of patients who received placebo (p<0.0001). Inrebic also improved the Total Symptom Score as measured by the modified Myelofibrosis Symptoms Assessment Form (MFSAF) v2.0 diary2 (night sweats, itching, abdominal discomfort, early satiety, pain under ribs on left side, bone or muscle pain) by 50% or greater when assessed from baseline to the end of cycle 6 in 40% of (36 of 89) patients treated with 400 mg, versus 9% (7 of 81) of patients who received placebo (p<0.0001.

Inrebic has a Boxed Warning for serious and fatal encephalopathy, including Wernicke’s. Serious encephalopathy was reported in 1.3% (8 of 608) of patients treated with Inrebic in clinical trials and 0.16% (1 of 608) of the cases were fatal. Wernicke’s encephalopathy is a neurologic emergency resulting from thiamine (Vitamin B1) deficiency. Thiamine levels should be assessed in all patients prior to starting Inrebic, periodically during treatment, and as clinically indicated. Do not start Inrebic in patients with thiamine deficiency; replete thiamine prior to treatment initiation. If encephalopathy is suspected, immediately discontinue Inrebic and initiate parenteral thiamine. Monitor until symptoms resolve or improve and thiamine levels normalize.