Last reviewed 2026-04-20 · How we verify

Inrebic (FEDRATINIB)

Inrebic works by blocking the activity of Cyclin-G-associated kinase, a protein involved in the proliferation and survival of bone marrow cells.

Inrebic (FEDRATINIB) is a small molecule modality developed by IMPACT and currently owned by Bristol-Myers. It targets Cyclin-G-associated kinase to treat Myelofibrosis, a condition characterized by the scarring of bone marrow. Inrebic was FDA-approved in 2019 for its approved indications. The commercial status of Inrebic is patented, with no generic manufacturers available. Key safety considerations include its half-life of 41 hours.

At a glance

Mechanism of action

Fedratinib is an oral kinase inhibitor with activity against wild type and mutationally activated Janus Associated Kinase (JAK2) and FMS-like tyrosine kinase (FLT3). Fedratinib is 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. In cell models expressing mutationally active JAK2V617F or FLT3ITD, fedratinib reduced phosphorylation of signal transducer and activator of transcription (STAT3/5) proteins, inhibited cell proliferation, and induced apoptotic cell death. In mouse models of JAK2V617F-driven myeloproliferative disease, fedratinib blocked phosphorylation of STAT3/5, and improved survival, white blood cell counts, hematocrit, splenomegaly, and fibrosis.

Approved indications

• Myelofibrosis
• Post-essential thrombocythaemia myelofibrosis
• Post-polycythaemia vera myelofibrosis
• Primary myelofibrosis

Boxed warnings

• WARNING: ENCEPHALOPATHY INCLUDING WERNICKE'S Serious and fatal encephalopathy, including Wernicke's, has occurred in patients treated with INREBIC. Wernicke's encephalopathy is a neurologic emergency. Assess thiamine levels in all patients prior to starting INREBIC. Do not start INREBIC in patients with thiamine deficiency; replete thiamine prior to treatment initiation. While on treatment all patients should receive prophylaxis with daily oral thiamine and should have thiamine levels assessed as clinically indicated. If encephalopathy is suspected, immediately discontinue INREBIC and initiate parenteral thiamine. Monitor until symptoms resolve or improve and thiamine levels normalize [see Dosage and Administration (2.6) , Warnings and Precautions (5.1) and Adverse Reactions (6.1) ] . WARNING: ENCEPHALOPATHY INCLUDING WERNICKE'S See full prescribing information for complete boxed warning. Serious and fatal encephalopathy, including Wernicke's, has occurred in patients treated with INREBIC. Wernicke's encephalopathy is a neurologic emergency. Assess thiamine levels in all patients prior to starting INREBIC. Do not start INREBIC in patients with thiamine deficiency; replete thiamine prior to treatment initiation. While on treatment all patients should receive prophylaxis with daily oral thiamine and should have thiamine levels assessed as clinically indicated. If encephalopathy is suspected, immediately discontinue INREBIC and initiate parenteral thiamine. Monitor until symptoms resolve or improve and thiamine levels normalize. ( 2.6 , 5.1 , 6.1 ).

Common side effects

• Diarrhea
• Nausea
• Anemia
• Vomiting
• Fatigue or asthenia

Drug interactions

• Strong CYP3A4 Inhibitors
• Strong and Moderate CYP3A4 Inducers
• Dual CYP3A4 and CYP2C19 Inhibitors
• CYP3A4, CYP2C19, or CYP2D6 Substrates
• OCT2 and MATE1/2-K Substrates

Key clinical trials

• Decitabine With Ruxolitinib, Fedratinib or Pacritinib for the Treatment of Accelerated/Blast Phase Myeloproliferative Neoplasms (PHASE2)
• Reduced Intensity Haploidentical Transplantation for the Treatment of Primary or Secondary Myelofibrosis (PHASE2)
• Fedratinib in Combination With Nivolumab (PHASE2)
• Fedratinib in Myelodysplastic /Myeloproliferative Neoplasms (MDS/MPNs) and Chronic Neutrophilic Leukemia (CNL) (PHASE2)
• Maintenance Fedratinib to Prevent Post-Transplant Relapse in Myeloproliferative Neoplasms (PHASE1)
• A Study of Fedratinib in Japanese Subjects With DIPSS (Dynamic International Prognostic Scoring System)- Intermediate or High-risk Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (Post-PV MF), or Post-essential Thrombocythemia Myelofibrosis (Post-ET MF) (PHASE1,PHASE2)
• A Study to Evaluate Single Agent Selinexor Versus Physician's Choice in Participants With Previously Treated Myelofibrosis (PHASE2)
• A Study to Assess the Safety and Tolerability of BMS-986158 Alone and in Combination With Either Ruxolitinib or Fedratinib in Participants With Blood Cancer (Myelofibrosis) (PHASE1,PHASE2)

Patents

Primary sources

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