Clinical Trials

* On December 5, 2015, Novartis announced  that a separate Phase III study met its primary endpoint-patients with polycythemia vera (PV) resistant to or intolerant of hydroxyurea who did not have an enlarged spleen who were treated with Jakavi® maintained hematocrit control without the need for phlebotomy. In the Phase III RESPONSE 2 (Randomized Study of Efficacy and Safety in POlycythemia Vera with JAK INhibitor Ruxolitinib VerSus BEst Available Care) study, the safety profile of Jakavi® was consistent with previous studies. Full results from the trial continue to be evaluated and will be presented at a future medical congress.
* On January 28, 2015, Novartis announced The New England Journal of Medicine (NEJM) published results from the pivotal Phase III clinical trial demonstrating Jakavi® (ruxolitinib) significantly improved hematocrit control 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 polycythemia vera who had an inadequate response to or unacceptable side effects from hydroxyurea as defined according to the modified European LeukemiaNet (ELN) criteria (1). In polycythemia vera, hematocrit control and spleen size reduction are key measures of a patient's response to therapy. At week 32 of the study, 77% of patients randomized to ruxolitinib achieved one or both components of the composite endpoint of hematocrit control (volume percentage of red blood cells in whole blood) without use of phlebotomy or spleen size reduction in comparison with 20% of patients randomized to standard therapy. A significantly greater proportion of patients achieved the composite primary endpoint when treated with ruxolitinib compared to standard therapy (21% compared to 1%, respectively; p<0.001), and 91% of these patients treated with ruxolitinib maintained their response at week 48.

In the study, a 50% or more improvement in polycythemia vera-related symptoms was seen in 49% of ruxolitinib-treated patients compared to 5% of patients treated with standard therapy. Patients treated with ruxolitinib also experienced a reduction in night sweats and itchiness (approximately 99% and 95%, respectively). In addition, a greater proportion of patients in the ruxolitinib treatment arm achieved complete hematologic remission as defined by modified ELN criteria, a key secondary endpoint, when compared to the standard therapy arm (24% compared to 9%, respectively; p=0.003). Complete hematologic remission was defined as achieving hematocrit control without the use of phlebotomy, platelet count <=400 x 109/L and white blood cell count <=10 × 109/L, which are all important markers of disease control in polycythemia vera.

The data also showed fewer patients treated with ruxolitinib experienced thromboembolic events when compared to those who received standard therapy (1 patient compared to 6 patients within the first 32 weeks, respectively), a key treatment objective in polycythemia vera as patients are at a high risk for cardiovascular complications. Overall, ruxolitinib was well tolerated, and non-hematologic adverse events (AEs) were consistent with those previously seen in ruxolitinib studies in PV and myelofibrosis. Within the first 32 weeks of treatment, the most common Grade 3 or 4 hematologic abnormalities in the ruxolitinib treatment arm were anemia (2%) and thrombocytopenia (5%). The most common non-hematologic AEs in the ruxolitinib arm were headache, diarrhea and fatigue, which were mainly Grade 1 or 2. Additionally, nearly 85% of patients randomized to ruxolitinib were still receiving treatment at a median follow-up of 81 weeks.

Based on the Phase III data, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recently adopted a positive opinion for ruxolitinib for the treatment of adult patients with polycythemia vera who are resistant to or intolerant of hydroxyurea. Ruxolitinib is currently approved in more than 70 countries for patients with myelofibrosis, a debilitating and life-threatening blood cancer.

(1) Vannucchi A, et al. Ruxolitinib versus Standard Therapy for the Treatment of Polycythemia Vera. The New England Journal of Medicine. 2015;372:426-35.

* On June 3, 2014, Incyte and Novartis announced results from the RESPONSE trial, the first pivotal Phase III study evaluating a JAK1/JAK2 inhibitor for the treatment of polycythaemia vera (PV). Ruxolitinib, compared to best available therapy (BAT), significantly improved hematocrit control without the need for phlebotomy and reduced spleen size in patients with uncontrolled PV -- those who are resistant to or intolerant of hydroxyurea (HU). Findings from the RESPONSE study are being presented in an oral presentation at the 50th Annual Meeting of the American Society of Clinical Oncology in Chicago.

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. These data will support global regulatory filings anticipated this year, including a submission to the FDA expected this month.

* On March 7, 2014, Novartis has announced that a pivotal Phase III trial of Jakavi® (ruxolitinib) compared to best available therapy has met its primary endpoint of maintaining 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 reducing spleen size by 35 percent or more in patients with polycythaemia vera resistant to or intolerant of hydroxyurea. The safety profile of ruxolitinib was generally consistent with previous studies based on initial review of the data. Data from the study (RESPONSE) will be presented at an upcoming medical congress and submitted to worldwide regulatory authorities this year.