U.S. Food and Drug Administration Approval: Ruxolitinib for the Treatment of Patients with Intermediate and High-Risk Myelofibrosis

• Published in: Clinical cancer research Vol. 18; no. 12; pp. 3212 - 3217
• Main Authors: DEISSEROTH, Albert, KAMINSKAS, Edvardas, BULLOCK, Julie, BURKE, Laurie B, RAHMAN, Atiqur, SRIDHARA, Rajeshwari, FARRELL, Ann, PAZDUR, Richard, GRILLO, Joseph, WEI CHEN, SABER, Haleh, LU, Hong L, ROTHMANN, Mark D, BRAR, Satjit, JIAN WANG, GARNETT, Christine
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.06.2012
• Subjects: Anemia - chemically induced; Antineoplastic agents; Biological and medical sciences; Clinical Trials, Phase III as Topic; Drug Approval; Female; Hematologic and hematopoietic diseases; Humans; Janus Kinase 1 - antagonists & inhibitors; Janus Kinase 2 - antagonists & inhibitors; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Neutropenia - chemically induced; Pharmacology. Drug treatments; Primary Myelofibrosis - drug therapy; Pyrazoles - adverse effects; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; Randomized Controlled Trials as Topic; Thrombocytopenia - chemically induced; United States; United States Food and Drug Administration; United States; Human; Myeloproliferative syndrome; High risk; Myelofibrosis; Treatment; Patient; Hemopathy; Food and Drug Administration
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-12-0653

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.