New Targeted Therapy Approved for Polycythemia Vera

A new targeted therapy is being greenlighted for treating patients with polycythemia vera (PV) who have failed or could not tolerate hydroxyurea.  The US Food and Drug Administration (FDA) on December 4, 2014 approved  ruxolitinib (Jakafi), which inhibits Janus Associated Kinase (JAK) 1 and 2.  

Polycythemia vera 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. PV is driven by the dysregulation of the JAK-STAT pathway.  Richard Pazdur, MD, who is the director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said this is the first drug to be approved for this condition and underscores the importance of developing drugs that match the mechanisms of the disease.  This agent has been shown to be effective at reducing spleen size and the need for phlebotomies to control the disease.

The approval of this new agent is based in part on the results from the phase III RESPONSE clinical trial, which demonstrated a significantly greater number of patients achieved a composite primary endpoint of hematocrit control without use of phlebotomy and spleen size reduction when treated with ruxolitinib compared to best available therapy (21% versus 1%).  The study also showed that a greater number of patients treated with ruxolitinib achieved complete hematologic remission and had a durable primary response at week 48 compared to patients treated with standard therapy (19% versus 1%).  

In a January 23, 2015 Novartis media release, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for ruxolitinib for the treatment of adult patients with PV who are resistant to or intolerant of hydroxyurea.  A final decision by the European Commission is expected within 90 days of the CHMP recommendation. Alessandro Riva, MD, who is Global Head of Novartis Oncology Development and Medical Affairs, said if ruxolitinib is approved in the EU, it will be the first ever targeted therapy for this condition and a positive step forward for helping patients with high unmet needs.

RESPONSE was a global, randomized, open-label trial, which was conducted at more than 90 trial sites and included 222 patients.  All the patients were resistant to or intolerant of hydroxyurea and were randomized 1:1 to receive either ruxolitinib (starting dose of 10 mg twice daily) or best available therapy.  

The most common side effects associated with ruxolitinib use were anemia and thrombocytopenia.  The most common non-blood related side effects included dizziness, constipation, and herpes zoster. The three most frequent non-hematological laboratory abnormalities associated with ruxolitinib use include hypercholesterolemia, elevated alanine aminotransferase (ALT), and elevated aspartate aminotransferase (AST) levels.