Inrebic

[Introduction to Inrebic]

INREBIC (Fedratinib) Fedratinib is a JAK2 inhibitor.

On August 16, 2019, the U.S. Food and Drug Administration approved Celgene’s JAK2 inhibitor Fedratinib (INREBIC, Impact Biomedicines, Inc) for the treatment of adults with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or essential thrombocythemia) myelofibrosis (MF). MF is a rare disease.

This is the second myelofibrosis drug approved by the FDA.

Before fedratinib, only Ruxolitinib (JAK1/2 inhibitor) from Novartis/Incyte was approved by the FDA in 2011 for the treatment of myelofibrosis.

The approval of INREBIC is another important milestone for Celgene and underscores our commitment to people living with blood cancers," said Celgene Chief Medical Officer Jay Backstrom, M.D.M.P.H.. "We are pleased to offer INREBIC as a new treatment option for patients with myelofibrosis, including those previously treated with ruxolitinib. ”

Approval date: August 16, 2019

Company: Celgene Corporation

INREBIC (fedratinib) capsules, for oral use

Initial US approval: 2019

[Inrebic mechanism of action]

Fedratinib is an oral kinase inhibitor with activity against wild-type and mutation-activated Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3) activities. Fedratinib is a JAK2 selective inhibitor with enhanced JAK2 inhibitory activity against family members JAK1, JAK3 and TYK2.

Aberrant activation of JAK2 is associated with myeloproliferative neoplasms (MPNs), including myelofibrosis and polycythemia vera. In expression of mutant active JAK2V617F or FLT3 In the cell model of ITD, fedratinib reduces the phosphorylation of signal transducer and activator of transcription (STAT3/5) proteins, inhibits cell proliferation, and induces apoptosis

Cell death. In a mouse model of JAK2V617F-driven myeloproliferative disease, fedratinib blocked STAT3/5 phosphorylation and improved survival, white blood cell count, hematocrit, splenomegaly, and fibrosis.

[Indications and Usage of Inrebic]

INREBIC is a kinase inhibitor indicated for the treatment of adult patients with intermediate 2 or high-risk primary or secondary (secondary polycythemia or post-essential thrombocythemia) myelofibrosis (MF).

[Inrebic dosage and administration]

Recommended dose: 400 mg orally once daily, with or without food, in patients with baseline platelet counts greater than or equal to 50 × 109/L.

Reduce dose in patients taking strong CYP3A inhibitors or with severe renal insufficiency.

[Inrebic dosage form and strength]

Capsules: 100 mg.

【Inrebic Contraindications】

No.

[Inrebic Warnings and Precautions]

Anemia and thrombocytopenia: Control by dose reduction, interruption, or transfusion.

Gastrointestinal Toxicity: If a patient develops severe diarrhea, nausea, or vomiting, control by dose reduction or interruption. Antiemetics and antibiotics are recommended Diarrhea drug treatment.

Hepatotoxicity: Manage by dose reduction or interruption.

Amylase and lipase elevations: Manage by dose reduction or interruption.

[Inrebic Adverse Reactions]

The most common adverse reactions (≥20%) are diarrhea, nausea, anemia and vomiting.

【Inr ebic drug interactions]

Strong CYP3A4 inhibitors: Reduced INREBIC dose is recommended.

Powerful and Moderate CYP3A4 Inducers: Avoid use of INREBIC.

Dual CYP3A4 and CYP2C19 inhibitors: Avoid use of INREBIC.

[Inrebic is used for specific groups of people]

Lactation period: It is recommended not to breastfeed.

Severe hepatic impairment: Avoid use of INREBIC.

[Inrebic Packaging Provision and Handling]

Provide

INREBIC (fedratinib) 100 mg capsules: reddish brown, opaque, size 0 capsule, printed with white ink "FEDR 100mg".

•120 Capsules (NDC 59572-720-12)

[Inrebic Storage]

Storage temperature below 86°F (30°C).