Ruxolitinib Improves Outcomes for Patients With Polycythemia Vera in Phase III Study

Ruxolitinib, a JAK1/2 inhibitor, is the first treatment to demonstrate efficacy in a phase III trial for patients with polycythemia vera (PV), a chronic, incurable blood cancer with limited treatment options

Ruxolitinib, a JAK1/2 inhibitor, is the first treatment to demonstrate efficacy in a phase III trial for patients with polycythemia vera (PV), a chronic, incurable blood cancer with limited treatment options, Novartis, the drug’s developer, announced today.

These data, announced in a Novartis press release, showed that ruxolitinib met the primary endpoint of maintaining hematocrit control and reducing spleen size when compared with best available therapy in patients who are resistant or intolerant of hydroxyurea

"We are encouraged by these pivotal phase III trial results, which show the potential of ruxolitinib to help patients with polycythemia vera," said Alessandro Riva, president, Novartis Oncology and interim and global head, Oncology Development and Medical Affairs in the press release. "We plan to submit these data to worldwide regulatory agencies this year, as we seek to bring ruxolitinib to patients with polycythemia vera who are no longer responding to or are intolerant of prior therapy."

PV causes an overproduction of blood cells, which leads to a thickening of the blood and increased risk of blood clots.1 These blood clots can cause cardiovascular complications such as stroke and heart attack.2 Patients with PV often have enlarged spleen and additional debilitating symptoms.1 Many patients who are treated with common therapies become intolerant or resistant to these treatments, leading to an increased risk of progression.3,4

Almost all patients with PV have dysregulated JAK signaling, with ~95% of patients harboring the JAK2V617F mutation.5

The safety profile of ruxolitinib was generally consistent with previous studies based on initial review of the data from the RESPONSE study, according to the Novartis press release.

The global, randomized, open-label RESPONSE study was conducted at 109 sites and randomized 222 patients with PV who were resistant or intolerant to hydroxyurea, an antineoplastic drug.

Patients were randomized 1:1 to receive either ruxolitinib (10 mg twice-daily) or best available therapy, which was defined as investigator-selected monotherapy or observation only. The dose was adjusted as needed throughout the study.

The primary endpoint of the study was the proportion of patients whose hematocrit was controlled without phlebotomy and whose spleen volume was reduced by 35% or more from baseline as assessed by imaging at 32 weeks. In addition to safety, key secondary endpoints include durable response and complete hematological remission.

According to Reuters, the results of this study put ruxolitinib on track to become a potential blockbuster treatment with sales of $1 billion-plus.

In an ongoing phase II trial, 73 patients with advanced PV or essential thrombocythemia received 10 mg, 25 mg, or 50 mg of ruxolitinib twice a day for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dosage, investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew their consent.

The 34 patients with PV who received ruxolitinib for a median of 35 months achieved durable control of hematocrit without phlebotomy, reduction in splenomegaly, and reduction in PV-related symptoms.6

In the ongoing phase III RELIEF study, the symptomatic benefit of ruxolitinib is being evaluated in patients with PV.

Currently, ruxolitinib is approved in over 55 countries for patients with myelofibrosis.


  1. Leukemia & Lymphoma Society. Polycythemia Vera Facts. June 2012. Available at Accessed 3/7/14.
  2. Finazzi G, Barbui T. How I treat patients with polycythemia vera. Blood. 2007;109(12):5104-5111.
  3. Alvarez-Larrán A, Pereira A, Cervantes F, et al. Assessment and prognostic value of the European LeukemiaNet criteria for clinicohematologic response, resistance, and intolerance to hydroxyurea in polycythemia vera. Blood. 2012;119(6):1363-1369.
  4. Najean Y, Dresch C, Rain JD. The very-long-term course of polycythaemia: a complement to the previously published data of the Polycythaemia Vera Study Group. Br J Haematol. 1994;86(1):233-235.
  5. Vannucchi AM, Guglielmelli P, Tefferi A. Advances in understanding and management of myeloproliferative neoplasms. CA Cancer J Clin. 2009;59:171-191.
  6. Verstovsek S, Passamonti F, Rambaldi A, et al. A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea. Cancer. 2013 Oct 30. doi: 10.1002/cncr.28441.[Epub ahead of print].