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Jakavi found superior to standard therapy for Polycythemia Vera

 

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Novartis announced 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 (PV) who had an inadequate response to or unacceptable side effects from hydroxyurea as defined according to the modified European LeukemiaNet (ELN) criteria, which is published in The New England Journal of Medicine (NEJM). In PV, hematocrit control and spleen size reduction are key measures of a patient's response to therapy.

PV is a chronic, incurable blood cancer associated with an overproduction of blood cells that can cause serious cardiovascular complications, such as stroke and heart attack and affects roughly one to three people per 100,000 globally. The disease is driven by the dysregulation of the JAK-STAT pathway. It is typically characterized by elevated hematocrit, the volume percentage of red blood cells in whole blood, which can lead to a thickening of the blood and an increased risk of blood clots, as well as an elevated white blood cell and platelet count.

Approximately 25% of patients with PV develop resistance to or intolerance of hydroxyurea and are considered to have uncontrolled disease, which is typically defined as hematocrit levels greater than 45%, elevated white blood cell count and/or platelet count, and may be accompanied by debilitating symptoms and/or enlarged spleen. Elevated white blood cell count and hematocrit are also associated with an increased risk of blood clots.

"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 very limited alternative treatment options to effectively manage the disease," said Dr. Alessandro M. Vannucchi, Azienda Ospedaliera Universitaria Careggi, University of Florence, Italy and lead study author. "This study indicates that ruxolitinib may represent an important advance for this population of patients with PV, a disease that can lead to serious complications and difficult daily symptoms."

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.

"A high unmet need exists for PV patients with uncontrolled disease on current treatments, and if approved in the EU, ruxolitinib is expected to be the first-ever targeted therapy for patients with PV," said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. "We are working diligently with regulatory authorities to bring ruxolitinib to patients with PV who may benefit from this treatment."

In the study, a 50% or more improvement in PV-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 PV.

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 PV as patients are at a high risk for cardiovascular complications.

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 PV 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.


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