The FINANCIAL — Novartis on June 10 announced Phase III data from RESPONSE-2 showing that Jakavi (ruxolitinib) helped patients with polycythemia vera (PV), who did not have an enlarged spleen and were resistant to or intolerant of hydroxyurea, achieve superior hematocrit control compared to best available therapy (BAT) at 28 weeks (62.2% vs 18.7%, respectively; p<0.0001).
The findings were presented for the first time at the 21st Congress of the European Hematology Association (EHA) in Copenhagen, Denmark, according to Novartis.
Polycythemia vera is a rare and incurable blood cancer associated with an overproduction of blood cells that can cause serious cardiovascular complications, such as blood clots, stroke and heart attack. As the disease progresses, the spleen can become enlarged as it works to clear a greater number of blood cells than normal. In this study, patients did not have an enlarged spleen as assessed by physical examination at baseline (spleen palpation) and a majority (approximately 70%) were previously treated with hydroxyurea only, therefore considered less advanced. The remaining patients were treated with multiple lines of therapy (approximately 30%).
“RESPONSE-2 is the first study of this scale to focus on patients with inadequately controlled polycythemia vera in a less advanced phase of the disease,” said lead study investigator, Francesco Passamonti, MD, the University of Insubria, Varese, Italy. “The study supports the use of Jakavi as a second-line treatment option to help this patient population gain better control of their disease.”
Patients with PV in the study were classified as inadequately controlled based on the modified European LeukemiaNet (ELN) criteria, which defines resistance to or intolerance of hydroxyurea as hematocrit levels greater than 45%, elevated white blood cell count and/or platelet count, and the presence of hydroxyurea-related non-hematologic toxicities.
“Given the limited research and treatment options for polycythemia vera, this trial was initiated to gain a better understanding of Jakavi in patients whose disease is not adequately controlled with hydroxyurea,” said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. “The results demonstrate the potential benefit of Jakavi to help manage the disease in patients who have few other options.”
In addition to meeting its primary endpoint of proportion of patients achieving hematocrit control, the RESPONSE-2 study showed that nearly five times more patients with PV achieved complete hematologic remission with Jakavi compared to BAT at 28 weeks (23.0% vs 5.3%, respectively; p=0.0019). Patients taking Jakavi also experienced complete resolution of their symptoms related to PV compared to BAT (50.0% vs 7.7%, respectively). Overall, Jakavi was well tolerated. Findings from this study are consistent with data from the RESPONSE pivotal trial evaluating patients with inadequately controlled PV with an enlarged spleen.
Additionally, Phase III data from the COMFORT-I study were also presented at EHA. These data suggest an overall survival advantage in patients with intermediate-2 or high-risk myelofibrosis (MF) randomized to Jakavi compared to patients randomized to placebo. The five-year survival showed a 31% reduced risk of death (HR=0.69; 95% CI: 0.50, 0.96; p=0.025) in the Jakavi arm despite more than 70% of patients randomized to the placebo arm crossing over to receive treatment with Jakavi (median time to crossover was 41.1 weeks). Patients treated with Jakavi maintained spleen response (>=35% reduction in size) for an average of three years. These findings further support the durable efficacy and long-term safety profile of Jakavi in MF.