Ruxolitinib


Ruxolitinib 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 when there has been an inadequate response to or intolerance of hydroxyurea. Ruxolitinib has also been shown to improve cases of chronic graft versus host disease in patients following a bone marrow transplant. It was developed and is currently sold by Incyte Corp in the US under the brand name Jakafi, and by Novartis elsewhere in the world, under the brand name Jakavi.

Mechanism of action

Ruxolitinib is a janus kinase inhibitor with selectivity for subtypes JAK1 and JAK2. Ruxolitinib inhibits dysregulated JAK signaling associated with myelofibrosis. JAK1 and JAK2 recruit signal transducers and activators of transcription to cytokine receptors leading to modulation of gene expression.

Side effects

Side effects include pancytopenia, thrombocytopenia, anemia 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 and case reports of opportunistic infections. Metabolic side effects have included weight gain. Laboratory abnormalities have included alanine transaminase abnormalities, aspartate transaminase abnormalities, and mildly elevated cholesterol levels.

Approval

The phase III Controlled Myelofibrosis Study with Oral JAK Inhibitor-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 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 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, alopecia areata, relapsed diffuse large B-cell lymphoma, and peripheral T-cell lymphoma.
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.
As of September 2019. a clinical trial was in progress to evaluate "Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors".