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FDA Approval for Ruxolitinib Phosphate

Brand name: JakafiTM

  • Approved for intermediate and high risk myelofibrosis

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

On November 16, 2011, the Food and Drug Administration (FDA) approved ruxolitinib phosphate (JakafiTM oral tablets, made by Incyte Corporation) for the treatment of intermediate and high risk  myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Results of two randomized controlled trials in patients with intermediate or high risk myelofibrosis comparing ruxolitinib phosphate to placebo (Study 1) or to best available therapy (Study 2) were the basis of approval.

Study 1 was a double-blind randomized placebo-controlled study allocating 309 patients (1:1) to either ruxolitinib phosphate (15-20 mg orally twice daily) or placebo. Fifty percent of patients had primary myelofibrosis, 31 percent had post-polycythemia vera myelofibrosis, and 18 percent had post-essential thrombocythemia myelofibrosis. Study 2 was an open-label trial allocating 219 patients (2:1) to either ruxolitinib phosphate (15-20 mg orally twice daily) or best available therapy. Fifty-three percent of patients had primary myelofibrosis, 31 percent had post-polycythemia vera myelofibrosis, and 16 percent had post-essential thrombocythemia myelofibrosis. The ruxolitinib phosphate starting dose in both trials was based on the entry platelet counts.

Ruxolitinib phosphate treatment in both trials continued as long as the patients continued to benefit or until unacceptable toxicity. The primary endpoint  was a comparison of the proportion of patients in the two groups who achieved at least a 35 percent reduction in spleen volume (by CAT scan or MRI) after 24 weeks (Study 1) or after 48 weeks of treatment (Study 2).

Both randomized trials achieved their prespecified primary endpoints. In Study 1, 42 percent of patients treated with ruxolitinib phosphate, compared with 1 percent of patients treated with placebo, experienced at least a 35 percent reduction of spleen volume at 24 weeks (p<0.0001, Chi-square and Fisher’s exact test). In Study 2, 29 percent of patients treated with ruxolitinib phosphate, compared with 0 percent of patients treated with best available therapy, experienced at least a 35 percent reduction of spleen volume at 48 weeks (p<0.0001, Cochran-Mantel-Haenszel test).

The key secondary endpoint for Study 1 was to determine the difference between the proportion of patients treated with ruxolitinib phosphate compared with the proportion of patients treated with placebo who experienced at least a 50 percent reduction of a total symptom score.  This symptom score evaluated abdominal discomfort, pain under the left ribs, night sweats, itching, bone/muscle pain, and early satiety at 24 weeks compared to baseline. Forty-six percent of patients treated with ruxolitinib phosphate, compared with 5 percent of patients treated with placebo, achieved at least a 50 percent reduction of the total symptom score at 24 weeks (p<0.0001, Chi-square test).

The key secondary endpoint on Study 2 was to determine the difference between the two treatment groups in the proportion of patients who achieved at least a 35 percent reduction in spleen volume (by CAT scan or MRI) at 24 weeks of treatment. Thirty-two percent of the patients treated with ruxolitinib phosphate achieved at least a 35 percent reduction in spleen volume, compared with 0 percent of patients treated with best available therapy (p <0.0001, Chochran-Mantel-Haenszel test). 

At the time of approval, 75 percent of the patients on Study 1 and 67 percent on Study 2 who achieved at least a 35 percent reduction in spleen volume maintained this reduction in spleen volume.

The most common adverse drug reactions, observed in at least 1 percent of the patients treated with ruxolitinib phosphate, included thrombocytopenia, anemia, bruising, dizziness, and headache. Adverse drug reactions (grade 3 or greater) that were higher in patients treated with ruxolitinib phosphate compared with patients treated with placebo in Study 1 included thrombocytopenia (experienced by 13 percent of patients treated with ruxolitinib phosphate, compared with 1 percent of patients treated with placebo) and anemia (experienced by 45 percent of patients treated with ruxolitinib phosphate, compared with 19 percent of patients treated with placebo). Similar results were observed in Study 2.

The recommended starting dose of ruxolitinib phosphate is 20 mg orally twice daily for patients with a platelet count above 200 X 109/L and 15 mg orally twice daily for patients with a platelet count between 100 and 200 X 109/L.

This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.

The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.

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  • Updated: July 3, 2013