Home » Drug Information » FDA Approved Drugs » 2011
Medical Areas: Hematology
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The following drug information is obtained from various newswires, published
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Approval Status: Approved November 2011
Treatment Area: myelofibrosis
Jakafi (ruxolitinib) is a kinase inhibitor and inhibits Janus Associated Kinases (JAKs) JAK1 and JAK2, which mediate the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. Myelofibrosis is a myeloproliferative neoplasm known to be associated with dysregulated JAK1 and JAK2 signaling.
Jakafi is specifically approved for intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis.
Jakafi is supplied as a tablet for oral administration. The recommended initial dose is based on platelet count. A complete blood count (CBC) and platelet count must be performed before initiating therapy, every 2 to 4 weeks until doses are stabilized, and then as clinically indicated. The proposed starting doses are as follows:
Platelet Count greater than 200 X 10(9)/L - Starting Dose 20 mg orally twice daily
Platelet Count 100 X 10(9)/L to 200 X 10(9)/L - Starting Dose 15 mg orally twice daily.
The FDA approval of Jakafi was based on two randomized phase III studies (Studies 1 and 2). In both studies, subjects had palpable splenomegaly at least 5 cm below the costal margin and risk category of intermediate 2 or high risk. The starting dose of Jakafi was based on platelet count. Subjects with a platelet count between 100 and 200 X 10(9)/L were started on Jakafi 15 mg twice daily and subjects with a platelet count greater than 200 X 10(9)/L were started on Jakafi 20 mg twice daily. Doses were then individualized based upon tolerability and efficacy.
This double-blind, randomized, placebo-controlled study enrolled 309 subjects who were refractory to or were not candidates for available therapy. The subjects received Jakafi or matching placebo. The primary efficacy endpoint was the proportion of patients achieving greater than or equal to a 35% reduction from baseline in spleen volume at Week 24 as measured by MRI or CT.
This open-label, randomized study in enrolled 219 subjects who received Jakafi or best available therapy. The primary efficacy endpoint was the proportion of patients achieving greater than or equal to a 35% reduction from baseline in spleen volume at Week 48 as measured by MRI or CT.
A significantly larger proportion of subjects in the Jakafi group achieved a 35% or greater reduction in spleen volume from baseline in both studies compared to placebo in Study 1 and best available therapy in Study 2. A similar proportion of subjects in the Jakafi group achieved a 50% or greater reduction in palpable spleen length. In Study 1, 65% of subjects in the Jakafi arm reached the primay endpoint versus 1% in the placebo arm (p< 0.0001). In Study 2, 41% of subjects in the jakafi arm reached the primary endpoint versus 0% in the placebo arm (p< 0.0001).
Adverse events associated with the use of Jakafi may include, but are not limited to, the following:
Mechanism of Action
Jakafi (ruxolitinib) is a kinase inhibitor and inhibits Janus Associated Kinases (JAKs) JAK1 and JAK2, which mediate the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. JAK signaling involves recruitment of STATs (signal transducers and activators of transcription) to cytokine receptors, activation and subsequent localization of STATs to the nucleus leading to modulation of gene expression. Myelofibrosis is a myeloproliferative neoplasm known to be associated with dysregulated JAK1 and JAK2 signaling.
Ostojic A, Vrhovac R, Verstovsek S Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. Future Oncology 2011 Sep;7(9):1035-43
Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA, Estrov Z, Fridman JS, Bradley EC, Erickson-Viitanen S, Vaddi K, Levy R, Tefferi A Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. The New England Journal of Medicine 2009 Nov;116(11):2141-8.e1
For additional information regarding Jakafi or myelofibrosis, please visit the Jakafi web page.