Ruxolitinib Approval Marks New Treatment Option for Patients With Polycythemia Vera

Richard Pazdur, MD

The FDA has approved the JAK1/2 inhibitor ruxolitinib (Jakafi) as a treatment for patients with polycythemia vera (PV) 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 PV.

Approximately 100,000 patients in the United States are living with PV, noted Incyte Corporation, the drug’s manufacturer, and approximately one in four patients with PV are considered uncontrolled because they have an inadequate response to or are intolerant of hydroxyurea.

“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.

In the RESPONSE trial, 222 patients with PV 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 twice daily for 33.7% of patients, and 32.7% received the drug at 15 mg. Doses ranged from <10 mg to 25 mg twice daily.

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.

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.

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.

“Being diagnosed with a serious disease affects a person in a way that cannot be predicted,” said Robert Rosen, a patient living with PV and founder and chairman of the MPN Research Foundation. “The FDA approval of this drug is good news for our community and provides a new treatment option for those patients who do not respond to other therapies.”

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 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.”