FDA Approval for Ruxolitinib Phosphate

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Brand name: JakafiTM

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

Approved for polycythemia vera  

On December 4, 2014, the Food and Drug Administration (FDA) approved ruxolitinib (Jakafi®, made by the Incyte Corporation) to treat patients with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea.  

The approval was based on superior response (a composite endpoint defined by durable hematocrit control and reduced spleen volume at 32 weeks) and durability of hematocrit control that obviated the need for regular phlebotomy. The multicenter open-label active-controlled trial (Protocol CINC424B2301) that led to the approval enrolled 222 patients with PV resistant to or intolerant of hydroxyurea. Patients were randomly assigned to receive either ruxolitinib 10 mg twice daily or best available care.   

Ruxolitinib was superior to best available therapy in achieving durable hematocrit control and spleen volume reduction at 32 weeks (21 percent vs 1 percent, p<0.0001) and at 48 weeks (19 percent vs 1 percent, p<0.0001). It also led to a relatively high rate of durable hematocrit control after 48 weeks (55 percent, 95 percent CI 45–64 percent).

Safety through week 32 was evaluated in the 110 subjects randomized to ruxolitinib. The most common hematologic adverse reactions (observed in 20 percent or more of patients) were thrombocytopenia and anemia. The most common nonhematologic adverse events (found in more than 10 percent of patients) were headache, abdominal pain, diarrhea, dizziness, fatigue, itching (pruritus), difficulty breathing, and muscle spasms. Four percent of patients treated with ruxolitinib discontinued treatment because of adverse events.

The recommended starting dose of ruxolitinib is 10 mg twice daily; however, patients taking strong CYP3A4 enzyme inhibitors or who have liver impairment or moderate-to-severe kidney impairment should take 5 mg twice daily. Doses may be titrated based on subsequent safety and efficacy evaluations.


Approved for intermediate and high risk myelofibrosis

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 Office of Hematology and Oncology 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.

  • Updated: April 23, 2015