Novartis has announced results from a new comparison study showing that Jakavi (ruxolitinib)-treated patients with polycythemia vera (PV), who were resistant or intolerant to hydroxyurea (HU), had a significantly reduced risk of thrombosis (blood clots) and death compared to PV patients who received best available therapy. The study findings are based on a comparison of patients in the phase III RESPONSE Jakavi clinical trial and the real-world Spanish GEMFINI patient registry. PV 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.

The new findings were presented at the 23rd Congress of the European Hematology Association (EHA) in Stockholm, Sweden.

"When you can complement clinical trial data with real-world experiences, it can provide valuable insight into how treatments affect patients in their day-to-day lives," said lead study investigator, Alberto Alvarez-Larran, MD, hematology department, hospital clinic, Barcelona, Spain. "This latest research supports the use of Jakavi to help people with polycythemia vera gain better control of their disease when hydroxyurea is not an option."

Additional Jakavi data presented at the EHA Annual Congress includes efficacy and safety analyses of the largest expanded access trial of myelofibrosis (MF) patients treated with Jakavi to date (JUMP). An efficacy analysis showed that patients with lower-risk MF achieved spleen size reductions when treated with Jakavi, with most patients (82.1%) achieving a >=50% reduction at any time. A separate analysis identified factors that may lead to a greater spleen response in patients with MF treated with Jakavi, including treating earlier in the course of the disease and at a higher dose (>=10 mg BID).

"With limited treatment options, patients with myeloproliferative neoplasms (MPNs) often struggle to keep their disease under control," said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. "The research conducted by Novartis teams and our physician partners in both PV and MF is helping to clarify how Jakavi can help relieve disease burden for patients."

Additionally, 48-week data from the EXPAND study support Jakavi 10 mg BID as a starting dose in patients with MF with low platelet counts, providing important information in a patient population at an increased risk of bleeding and serious complications. Nearly one-third of patients in the study treated with Jakavi achieved a >=50% reduction in spleen size at week 48 (31.8% of patients [7/22] with a platelet count of 75 to 99 x 109/L and 35.7% [5/14] of patients with a platelet count of 50 to 74 x 109/L).

The new data presented at EHA compares overall survival and thrombosis (blood clots) rates using data from patients treated in the Jakavi arm of the RESPONSE trial and patients treated in a real-world setting with best available therapy (BAT) from the Grupo Español de Enfermedades Mieloproliferativas Crónicas Filadelfia Negativas (GEMFIN) registry.

In the previously reported Phase III RESPONSE trial, the high rate of crossover from BAT to Jakavi precluded the comparison of overall survival and thrombosis rates. RESPONSE was a global, open-label study that included patients with PV resistant to or intolerant of hydroxyurea, who were randomized 1:1 to receive either Jakavi (starting dose of 10 mg twice daily) or BAT, which was defined as investigator-selected monotherapy or observation only. The GEMFIN registry patients in the real-world BAT group had resistance or intolerance to hydroxyurea according to the modified European Leukemia Net criteria and received hydroxyurea (44%), busulfan (10%), radioactive phosphorus (2%), interferon (6%), anagrelide (12%), other therapy (11%) or no cytoreductive therapy (26%). Some patients were also treated with multiple therapies.

In the GEMFIN study, patients treated with Jakavi had a significantly prolonged overall survival (HR=0.28 [0.11-0.72]) and a lower risk of blood clots (HR=0.21 [0.06-0.76]) when compared to real-world patients treated with BAT.

JUMP is an expanded access Phase IIIb study designed to further evaluate the safety and efficacy of Jakavi in MF. It includes the largest cohort of patients with MF treated with Jakavi, 2,233, to date. The study provided access to Jakavi for patients who had no access to the treatment outside of a clinical trial and included 60 patients who were determined to have DIPSS low-risk disease.

EXPAND is an open-label, Phase Ib, dose-finding study in patients with MF with baseline platelet counts of 50 to 99 x 109/L. Results presented at EHA are from the 48-week follow- period.

The study evaluated 10 mg BID as a safe starting dose of Jakavi. The key secondary endpoints are safety and efficacy, including proportion of patients achieving >=50% of reduction in spleen size. Safety findings were also consistent with previous studies of Jakavi.

Myelofibrosis (MF) and polycythemia vera (PV) are part of a group of related and rare blood cancers called myeloproliferative neoplasms (MPNs) in which bone marrow cells responsible for the body's blood cells develop and function abnormally.

In patients with MF, the bone marrow can no longer produce enough normal blood cells, causing the spleen to enlarge. MF affects approximately one in every 100,000 people.

PV is associated with an overproduction of blood cells that can cause serious cardiovascular complications if left inadequately controlled, such as blood clots, stroke and heart attack. PV affects up to three per 100,000 people globally each year.

Jakavi (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. Jakavi is approved by the European Commission for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea and for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (MF) (also known as chronic idiopathic MF), post-polycythemia vera MF or post-essential thrombocythemia MF. Jakavi is approved in 101 countries for patients with MF, including EU countries, Switzerland, Canada, Japan and in more than 75 countries for patients with PV, including EU countries, Switzerland, Japan and Canada. The exact indication for Jakavi varies by country. Additional worldwide regulatory filings are underway in MF and PV.

Novartis licensed ruxolitinib from Incyte Corporation for development and commercialization outside the United States. Jakavi is marketed in the United States by Incyte Corporation as Jakafi for the treatment of patients with PV who have had an inadequate response to or are intolerant of hydroxyurea and for the treatment of patients with intermediate or high-risk MF.