* The trial met the primary composite endpoint of hematocrit control and at least a 35 percent reduction in spleen volume

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* 77 percent of patients treated with ruxolitinib versus 20 percent on best available therapy achieved one or both of the components of the primary endpoint

* Approximately half of patients in the ruxolitinib group had at least a 50 percent improvement in symptom score, compared with 5 percent on best available therapy

* Global regulatory filings are underway based on these data; if approved, ruxolitinib would be the first JAK1/JAK2 inhibitor available for PV patients

On June 3, 2014 Incyte reproted results from the RESPONSE trial, the first pivotal Phase III study evaluating a JAK1/JAK2 inhibitor for the treatment of polycythemia vera (PV). Ruxolitinib, compared to best available therapy (BAT), significantly improved hematocrit control (red blood cell volume) without the need for phlebotomy (a procedure to remove blood from the body to reduce the concentration of red blood cells) and reduced spleen size in patients with uncontrolled PV — those who are resistant to or intolerant of hydroxyurea (HU) (Press release Incyte, JUN 3, 2014, View Source;p=RssLanding&cat=news&id=1936911 [SID:1234500687]). Findings from the RESPONSE study are being presented in an oral presentation at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago.

"Patients with advanced PV whose disease is not well-managed with existing therapies are at increased risk for thrombosis and suffer from multiple debilitating symptoms," stated Srdan Verstovsek, M.D., Ph.D., Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. "Data from the RESPONSE trial demonstrated that treatment with ruxolitinib can consistently control hematocrit, reduce spleen size, and improve symptoms such as fatigue and itching. Importantly, there appears to be a lower rate of thrombosis in the ruxolitinib arm compared to best available therapy."

Seventy-seven percent of ruxolitinib-treated patients versus 20 percent on BAT achieved at least one component of the primary endpoint: hematocrit control from week 8 to 32 and/or at least a 35 percent reduction in spleen volume. A greater proportion of patients treated with ruxolitinib achieved the composite primary endpoint compared to BAT (21 percent vs 1 percent, respectively; P< .0001); 91 percent of patients in the ruxolitinib group achieving this endpoint maintained their response at week 48.

A greater proportion of patients in the ruxolitinib treatment arm had complete hematologic remission, a key secondary endpoint, when compared to the BAT arm (24 percent compared to 9 percent, P=.003). Patients treated with ruxolitinib also experienced meaningful improvements in PV-related symptoms: 49 percent, compared to 5 percent treated with BAT, had a 50 percent or greater improvement in symptom score at week 32 as measured by the 14-item MPN-SAF (Myeloproliferative Neoplasm Symptom Assessment Form). At week 32, one patient in the ruxolitinib group and six in the BAT group had a thromboembolic event.

At a median follow-up of 81 weeks, 85 percent of patients in the ruxolitinib arm were still receiving treatment. Because most patients in the BAT group crossed over to receive ruxolitinib therapy at week 32, adverse events were evaluated at this time when exposure between groups was similar. The most common non-hematologic adverse events of any grade in the ruxolitinib group compared to the BAT group were headache (16.4 percent vs 18.9 percent), diarrhea (14.5 percent vs 7.2 percent), fatigue (14.5 percent vs 15.3 percent), and pruritus (13.6 percent vs 22.5 percent). Based on laboratory assessments, the rates of new or worsening grade 3 or 4 anemia and thrombocytopenia in the ruxolitinib group versus the BAT group were 1.8 percent vs 0 percent and 5.5 percent vs 3.6 percent, respectively.

"One out of four patients with polycythemia vera remain uncontrolled, face a profound symptom burden and are at greater risk of cardiovascular complications such as stroke and heart attack," stated Hervé Hoppenot, President and Chief Executive Officer, Incyte. "These Phase III data give us confidence that ruxolitinib has the potential to become an important new treatment option for patients with uncontrolled PV who are no longer responding to or are intolerant of hydroxyurea."

These data will support global regulatory filings anticipated this year, including a submission to the U.S. Food and Drug Administration expected this month.

About the RESPONSE Trial

RESPONSE is an open-label randomized trial of 222 patients conducted in North America, Europe, Asia, and Australia. Patients with splenomegaly who were resistant to or intolerant of hydroxyurea (HU) and required phlebotomy were randomized 1:1 to receive ruxolitinib 10 mg twice daily or BAT, which was defined as investigator selected monotherapy or observation only. From week 32, patients in the BAT group could cross over to receive ruxolitinib therapy.

The primary endpoint of the study is the proportion of patients who achieved both hematocrit control without the need for phlebotomy from week 8 through 32 and a spleen volume reduction of at least 35 percent from baseline at 32 weeks. Key secondary endpoints include durable primary response and complete hematologic remission. Complete hematologic remission was defined as maintaining hematocrit control without the need for phlebotomy, a platelet count ≤400 x 109/L and white blood cell count ≤10 x 109/L. Other secondary endpoints include safety, symptom improvement, and quality of life.