FDA Approves Ruxolitinib for Polycythemia Vera

Richard Pazdur, MD

The FDA has approved the JAK1/2 inhibitor ruxolitinib (Jakafi) as a treatment for patients with polycythemia vera who are resistant or intolerant to hydroxyurea, based on findings from the phase III RESPONSE trial. The FDA’s action makes ruxolitinib the first treatment specifically approved for patients with polycythemia vera.

In the RESPONSE trial, hematocrit control without phlebotomy was achieved for 60% of patients treated with ruxolitinib compared with 20% receiving best available therapy. The primary endpoint of the trial looked specifically at the number of patients who achieved hematocrit control without phlebotomy from week 8 to 32 and experienced greater than a 35% reduction in spleen volume by week 32. Overall, 21% of patients in the ruxolitinib arm met this criteria compared with 1% for best available therapy, according to results presented at the 2014 ASCO Annual Meeting.

The FDA first approved ruxolitinib as a treatment for patients with intermediate and high-risk myelofibrosis in November 2011. This approval included the treatment of primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. This approval was based on results from two studies that demonstrated a reduction in spleen size with the treatment.

“The approval of Jakafi for polycythemia vera underscores the importance of developing drugs matched to our increasing knowledge of the mechanisms of diseases,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement. “The trial used to evaluate Jakafi confirmed clinically meaningful reductions in spleen size and the need for phlebotomies to control the disease.”

In the RESPONSE trial, 222 patients with polycythemia vera were randomized to ruxolitinib (n = 110) or best available therapy (n = 112), which included hydroxyurea, interferon, observation, and other treatments. By week 32, ruxolitinib was administered at 10 mg BID for 33.7% of patients and 32.7% received the drug at 15 mg. Doses ranged from <10 mg to 25 mg BID.

Approximately 95% of patients in both arms tested positive for a mutation in JAK2 V617F. Altogether, 96 patients in the best available therapy arm crossed over to receive ruxolitinib. Patient characteristics were balanced between the two arms.

Hematocrit control without phlebotomy was achieved for 60% of patients treated with ruxolitinib compared with 20% receiving best available therapy. Spleen volume was reduced by ≥35% in 38% of patients receiving ruxolitinib compared with 1% for best available therapy.

At week 32, 24% of patients treated with ruxolitinib achieved a complete hematologic remission (CHR) compared with 9% for best available therapy (P = .003). Additionally, 88.5% of patients maintained a CHR at week 48.

In total, 91% of patients maintained a response to ruxolitinib following 48 weeks of treatment. The probability of maintaining a primary response to ruxolitinib for 1 year was 94%. At a median follow-up of 81 weeks, 85% of patients randomized to ruxolitinib remained on therapy.

The rates of grade 3/4 anemia and thrombocytopenia were less in the ruxolitinib arm compared with best available therapy (1.8% vs 5.5% and 0% vs 3.6%, respectively). Symptom improvement by Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) favored ruxolitinib, with 49% of patients experiencing a ≥50% improvement from baseline compared with 5% for best available therapy.

“The approval of Jakafi represents an important advance for patients with uncontrolled PV. For the first time we are able to provide these patients a treatment that has been shown to provide effective and consistent control of their blood counts and reduce spleen volume,” Srdan Verstovsek, MD, PhD, Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, said in a statement.