Novartis drug Jakavi® recommended by CHMP for EU approval to treat adults with rare blood cancer polycythemia vera

• Polycythemia vera (PV) is associated with overproduction of blood cells that can cause serious cardiovascular complications, such as stroke and heart attack¹
• Clinical data show Jakavi^® (ruxolitinib) significantly improved hematocrit levels and reduced spleen size, key measures of disease control²
• CHMP opinion marks a key milestone towards ruxolitinib becoming the first targeted treatment option for patients with PV in the EU

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Jakavi^® (ruxolitinib) for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea². If approved in the EU, ruxolitinib could provide the first targeted treatment option for these patients.

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 attack¹. In PV, patients with resistance to or intolerance of hydroxyurea 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^1,3,4. Elevated white blood cell count and hematocrit are also associated with an increased risk of blood clots⁵.

“This positive CHMP opinion is encouraging news for patients with polycythemia vera who need effective treatment options,” said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. “If approved, ruxolitinib will be the first-ever targeted therapy for polycythemia vera in the EU, a positive step forward for the rare blood cancer community in Europe and a major development in Novartis’ continued commitment to help patients with high unmet needs.”

In the EU, the European Commission generally follows the recommendations of the CHMP and delivers its final decision within three months of the CHMP recommendation. The decision will be applicable to all 28 EU member states plus Iceland, Norway and Liechtenstein. Global regulatory applications for ruxolitinib in PV are currently ongoing, and further regulatory filings are under review by health authorities. Ruxolitinib, which is marketed in the US by Incyte Corporation as Jakafi^®, received approval in December 2014 from the US Food and Drug Administration (FDA) for the treatment of patients with PV who have had an inadequate response to or are intolerant of hydroxyurea.

The CHMP recommendation was based on results from the pivotal Phase III RESPONSE clinical trial demonstrating that a significantly greater proportion of patients achieved the composite primary endpoint of hematocrit control (volume percentage of red blood cells in whole blood) without use of phlebotomy (a procedure to remove blood from the body to reduce the concentration of red blood cells) and spleen size reduction when treated with ruxolitinib compared to best available therapy (21% compared to 1%, respectively; p<0.0001)¹,². In addition, a greater proportion of patients in the ruxolitinib treatment arm achieved complete hematologic remission, as defined by the modified 2009 European LeukemiaNet (ELN) criteria, when compared to the standard therapy arm (24% compared to 9%, respectively; p=0.003)². The data also showed more patients treated with ruxolitinib had a durable primary response at week 48 compared to patients treated with standard therapy (19% compared to 1%, respectively; (p<0.0001)².

Overall, ruxolitinib was well tolerated, and non-hematologic adverse events (AEs) were consistent with those previously seen in ruxolitinib studies in PV and myelofibrosis^2,6,7. Within the first 32 weeks of treatment, the most common Grade 3 or 4 hematologic AEs in the ruxolitinib treatment arm were anemia (1.8%) and thrombocytopenia (5.5%)². The most common non-hematologic AEs were dizziness (15.5%), constipation (8.2%) and herpes zoster (6.4%)². The three most frequent non-hematological laboratory abnormalities (any Grade) were hypercholesterolemia (30.0%), raised alanine aminotransferase (22.7%) and raised aspartate aminotransferase (20.9%), which were mainly Grade 1 and 2².

Novartis drug Jakavi® recommended by CHMP for EU approval to treat adults with rare blood cancer polycythemia vera

References

1. Leukemia & Lymphoma Society. “Polycythemia Vera Facts.” Available at: http://www.lls.org/content/nationalcontent/resourcecenter/
   freeeducationmaterials/mpd/pdf/polycythemiavera.pdf. Accessed on April 28, 2014.
2. Jakavi^® (ruxolitinib) Summary of Product Characteristics. Basel, Switzerland: Novartis Pharma AG; January 2015.
3. Alvarez-Larran A, 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. Finazzi G and Barbui T. How I Treat Patients with Polycythemia Vera. Blood. 2007;109(12):5104-5111.
6. Vannucchi, A, et al. Long-Term Outcomes from a Phase 3 Study Comparing Ruxolitinib with Best Available Therapy (BAT) for the Treatment of Myelofibrosis (MF): A 3 Year Update of Comfort II. Abstract #S1111.18^th Congress of European Hematology Association (EHA), 2013. Stockholm, Sweden.
7. Verstovsek S, Ruben M, Gotlib J, et al. Long-Term Outcome of Ruxolitinib Therapy in Patients with Myelofibrosis: 3-Year Update from COMFORT-I. Abstract #396. 55th American Society of Hematology (ASH) Annual Meeting and Exposition, 2013. New Orleans, LA.