General Information

Inrebic (fedratinib) is a kinase inhibitor.

Inrebic is specifically indicated for the treatment of adult patients with intermediate-2or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF).

Inrebic is supplied as a capsule for oral administration. The recommended dosage of Inrebic is 400 mg taken orally once daily for patients with a baseline platelet count of greater than or equal to 50 x 109/L.

Inrebic may be taken with or without food. Administration with a high fat meal may reduce the incidence of nausea and vomiting.

Modify the dose for patients using concomitant strong CYP3A4 inhibitors, and in patients with severe renal impairment (creatinine clearance (CLcr)15 mL/min to 29mL/min).

If a dose of Inrebic is missed, the next scheduled dose should be taken the following day.

Patients that are on treatment with ruxolitinib before the initiation of Inrebic must taper and discontinue according to the ruxolitinib prescribing information.

Clinical Results

FDA Approval

The FDA approval of Inrebic was based on multiple trials, including the phase 3 JAKARTA trial. The study included 289 patients randomized to receive either Inrebic 500 mg (n=97) or 400 mg (n=96) or placebo (n=96) across 94 sites in 24 countries. The primary endpoint was spleen response rate, defined as the proportion of patients achieving greater than or equal to a 35% reduction from baseline in spleen volume at the end of cycle 6 as measured by magnetic resonance imaging (MRI) or computerized tomography (CT) with a follow-up scan 4 weeks later. 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. Inrebic also improved secondary endpoints, including the Total Symptom Score as measured by the modified Myelofibrosis Symptoms Assessment Form (MFSAF).

Side Effects

Adverse effects associated with the use of Inrebic may include, but are not limited to, the following:

diarrhea

nausea

anemia

vomiting

The Inrebic drug label includes the following Black Box Warning: Serious and fatal encephalopathy, including Wernicke’s, has occurred in patients treated with Inrebic. Wernicke’s encephalopathyis a neurologic emergency. Assess thiamine levels 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.

Mechanism of Action

Inrebic (fedratinib) is an oral kinase inhibitor with activity against wild type and mutationally activated Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). Fedratinib is a JAK2-selective inhibitor with higher inhibitory activity for JAK2 over family members JAK1, JAK3 and TYK2. Abnormal activation of JAK2 is associated with myeloproliferative neoplasms (MPNs), including myelofibrosis and polycythemia vera.

Additional Information

For additional information regarding Inrebic or myelofibrosis, please visit the Celgene web page.