Rare Disease Report

Pivotal Trial Testing Rutoxilitib (Jakafi) for Treating Patients with Polycythemia Vera Published

JANUARY 29, 2015
James Radke

The New England Journal of Medicine (NEJM) published results from the pivotal Phase III RESPONSE clinical trial that led to the approval of ruxolitinib (Jakafi) for the treatment of patients with polycythemia vera (PV) who had an inadequate response to or had unacceptable side effects from hydroxyurea.

PV is a myeloproliferative neoplasm (MPN) typically characterized by elevated hematocrit that can lead an increased risk of blood clots. Approximately 100,000 patients in the US are living with PV and current standard treatment for PV is phlebotomy plus aspirin. When phlebotomy can no longer control PV, chemotherapy such as hydroxyurea, or interferon, is utilized. However, about 25% of patients have inadequate response to or had unacceptable side effects from hydroxyurea, the most commonly used chemotherapeutic agent for the treatment of PV. For those patients, ruxolitinib is the only approved treatment.

Dr. Alessandro M. Vannucchi, Department of Hematology, University of Florence, Italy and lead study author said in a press release:

 “This study indicates that ruxolitinib may represent an important advance for patients with uncontrolled PV.”

“A key challenge in treating patients with PV is the development of resistance or intolerance to currently available therapies such as hydroxyurea, which leaves us with no effective treatment options to manage the disease.”


RESPONSE was a global, randomized, open-label multicnetered Phase III study in which 222 patients with PV resistant to or intolerant of hydroxyurea were randomized 1:1 to receive either ruxolitinib (starting dose of 10 mg twice daily) or standard therapy (best available therapy), which was defined as investigator-selected monotherapy or observation only. Ruxolitinib dose could be adjusted as needed throughout the study.

The primary endpoint of the study was the proportion of patients whose hematocrit was controlled without phlebotomy eligibility from week 8 through 32 (with no more than one phlebotomy eligibility between randomization and week 8) and whose spleen volume was reduced by 35% or more from baseline as assessed by imaging at week 32. Phlebotomy eligibility was defined as hematocrit (volume percentage of red blood cells in whole blood) greater than 45% and that was ≥3 percentage points higher than baseline, or hematocrit greater than 48%, whichever was lower.

The study found a significantly greater proportion of patients achieved the primary endpoint when treated with ruxolitinib compared to standard therapy (21% compared to 1%, respectively; p<0.001) as measured at week 32. Furthermore, 91% of these patients treated with ruxolitinib maintained their response at week 48.  Further analysis revealed that the 60% of patients randomized to ruxolitinib achieved hematocrit control without use of phlebotomy in comparison with 20% of patients randomized to standard therapy and  38% of patients randomized to ruxolitinib achieved at least a 35% spleen volume reduction in comparison with 1% of patients randomized to standard therapy.  In addition, 77% of patients randomized to ruxolitinib achieved one or both components of the composite primary endpoint, in comparison with 20% of patients  randomized to standard therapy.
Rich  Levy, MD, Incyte’s EVP, Chief Drug Development and Medical Officer said:

“These data, together with those seen with Jakafi therapy in myelofibrosis, add further to our confidence in the potential therapeutic value of JAK inhibition in the treatment of patients with myeloproliferative neoplasms.”

The  most common non-hematologic  adverse eventss in the ruxolitinib arm were headache (16.4%), diarrhea (14.5%) and fatigue (14.5%), which were mainly Grade 1 or 21. During the first 32 weeks, grade 3/4 anemia or thrombocytopenia occurred in 2% and 5% of ruxolitinib patients, respectively, vs  0% and 4% of standard therapy patients.


Vannucchi A, et al. Ruxolitinib versus Standard Therapy for the Treatment of Polycythemia Vera. The New England Journal of Medicine. N Engl J Med 2015; 372:426-435. DOI: 10.1056/NEJMoa1409002

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