title: U.S. Food and Drug Administration approval: ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis.
abstract: On November 16, 2011, the U.S. Food and Drug Administration (FDA) granted full approval to ruxolitinib, (Jakafi; Incyte Corp.), an inhibitor of the Janus kinases 1 and 2, for the treatment of patients with intermediate- or high-risk myelofibrosis, including primary myelofibrosis, postpolycythemia vera myelofibrosis, and postessential thrombocythemia myelofibrosis. This approval was based on the results of 2 large randomized phase III trials that enrolled patients with intermediate-2 or high-risk myelofibrosis and compared ruxolitinib with placebo (study 1) or best available therapy (study 2). The primary efficacy endpoint was the proportion of patients who experienced a reduction in spleen volume of ≥ 35% at 24 weeks (study 1) or 48 weeks (study 2). The key secondary endpoint in study 1 was the proportion of patients who experienced a ≥ 50% improvement from baseline in myelofibrosis total symptom score at 24 weeks. The results of these studies showed that a greater proportion of patients treated with ruxolitinib experienced a ≥ 35% reduction in spleen volume as compared with those treated with placebo (42% vs. 1%, P < 0.0001) or best available therapy (29% vs. 0%, P < 0.0001). A greater proportion of patients in study 1 experienced a ≥ 50% reduction in the myelofibrosis total symptom score during treatment with ruxolitinib than with placebo (46% vs. 5%, P < 0.0001). Ruxolitinib treatment was associated with an increased incidence of grades III and IV anemia, thrombocytopenia, and neutropenia. This is the first drug approved for myelofibrosis.
authors.affiliation: Office of Hematology and Oncology Drug Products, Study Endpoints and Label Development, Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland 20993, USA. albert.deisseroth@fda.hhs.gov
authors.forename: Albert
authors.initials: A
authors.lastname: Deisseroth
authors.forename: Edvardas
authors.initials: E
authors.lastname: Kaminskas
authors.forename: Joseph
authors.initials: J
authors.lastname: Grillo
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Haleh
authors.initials: H
authors.lastname: Saber
authors.forename: Hong L
authors.initials: HL
authors.lastname: Lu
authors.forename: Mark D
authors.initials: MD
authors.lastname: Rothmann
authors.forename: Satjit
authors.initials: S
authors.lastname: Brar
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Christine
authors.initials: C
authors.lastname: Garnett
authors.forename: Julie
authors.initials: J
authors.lastname: Bullock
authors.forename: Laurie B
authors.initials: LB
authors.lastname: Burke
authors.forename: Atiqur
authors.initials: A
authors.lastname: Rahman
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.forename: Ann
authors.initials: A
authors.lastname: Farrell
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000740:Anemia / Q000139:chemically induced; D017326:Clinical Trials, Phase III as Topic; D017277:Drug Approval; D005260:Female; D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000188:drug therapy*; D011720:Pyrazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines; D016032:Randomized Controlled Trials as Topic; D013921:Thrombocytopenia / Q000139:chemically induced; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053613:Janus Kinase 1; D053614:Janus Kinase 2