Trade names Jakafi, Jakavi MedlinePlus a612006 | AHFS/Drugs.com Monograph Routes ofadministration By mouth, topical | |
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License data EU EMA: JakaviUS FDA: Ruxolitinib Pregnancycategory AU: CUS: C (Risk not ruled out) | ||
Ruxolitinib (trade names Jakafi JAK-ə-fye and Jakavi) is a drug for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative disorder that affects the bone marrow, and for polycythemia vera (PCV) when there has been an inadequate response to or intolerance of hydroxyurea.
Contents
Mechanism of action
Ruxolitinib is a janus kinase inhibitor with selectivity for subtypes JAK1 and JAK2 of this enzyme. Ruxolitinib inhibits dysregulated JAK signaling associated with myelofibrosis. JAK1 and JAK2 recruit signal transducers and activators of transcription (STATs) to cytokine receptors leading to modulation of gene expression.
Side effects
Side effects include thrombocytopenia (low blood platelet count), anemia (low red blood cell count) and neutropenia; risk of infection; symptom exacerbation if the medication is interrupted or discontinued; and non-melanoma skin cancer.
Immunologic side effects have included herpes zoster (shingles) and case reports of opportunistic infections. Metabolic side effects have included weight gain. Laboratory abnormalities have included alanine transaminase (ALT) abnormalities, aspartate transaminase (AST) abnormalities, and mildly elevated cholesterol levels.
Approval
The phase III Controlled Myelofibrosis Study with Oral JAK Inhibitor-I (COMFORT-I) and COMFORT-II trials showed significant benefits by reducing spleen size and relieving debilitating symptoms.
In November 2011, ruxolitinib was approved by the U.S. Food and Drug Administration (FDA) for the treatment of intermediate or high-risk myelofibrosis based on results of the COMFORT-I and COMFORT-II Trials.
In 2014, it was approved in polycythemia vera (PCV) when there has been an inadequate response to or intolerance of hydroxyurea, based on the RESPONSE trial.
Research
It is also being investigated for plaque psoriasis, and for alopecia areata.
In Feb 2016, a phase III trial for pancreatic cancer was terminated due to insufficient efficacy.
Eight weeks-treatment with ruxolitinib blunted senescent cell-mediated inhibition of adipogenesis and increased insulin sensitivity in 22-month-old mice.