Rare Disease Report

Incyte Submits sNDA For Jakafi to Treat Patients with Polycythemia Vera

AUGUST 06, 2014
James Radke

The U.S. Food and Drug Administration (FDA) has accepted the supplemental New Drug Application (sNDA) for Incyte’s Jakafi (ruxolitinib) as a potential treatment of patients with polycythemia vera who have had an inadequate response to, or are intolerant of, hydroxyurea.

Jakafi is currently approved for people with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post–polycythemia vera myelofibrosis and post–essential thrombocythemia myelofibrosis.  In the United States, Jakafi is marketed by Incyte. Outside the United States, Jakavi is marketed by Novartis.

Myelofibrosis is a rare bone marrow cancer in which bone marrow cells develop and function abnormally leading to fibrous scar tissue that leads to severe anemia, weakness, fatigue and an enlarged spleen and liver.
Myelofibrosis can occur on its own (primary myelofibrosis) or as a result of another bone marrow disorder such as polycythemia vera and  essential thrombocythemia – all of which Jakafi is currently approved for.
Incyte is now seeking to get Jakafi approved for polycythemia vera in addition to its indication for myelofibrosis following polycythemia vera.

Polycythemia vera, like myelofibrosis, is a myeloproliferative neoplasm.  Polycythemia vera is characterized by an overproduction of normal red blood cells, white blood cells and platelets that leads to an increased risk of thrombosis. The most prominent feature of polycythemia vera is erythrocytosis (elevated red blood cell mass) which distinguish it from other myeloproliferative neoplasms.

At present there is no orphan drug approved for polycythemia vera but many patients may benefit from off-label treatment with hydroxyurea (Hydrea, Doxia). It is estimated that approximately 25% of the ~100,000 patients in the United States with polycythemia vera develop resistance, or intolerance, to hydroxyurea and patients with uncontrolled polycythemia vera have an increased risk of cardiovascular complications such as stroke, pulmonary embolism, deep vein thrombosis and heart attack.

In a press release, Richard Levy, M.D., Executive Vice President and Chief Drug Development and Medical Officer of Incyte said, “We are pleased to have received the acceptance of our sNDA filing by the FDA, and we believe that the submission contains a robust data set.”  The robust date Dr Levy referred to is from the RESPONSE Phase III trial, which was presented at the 2014 American Society of Clinical Oncology (ASCO) annual meeting in June by Verstovsek and colleagues.


In the RESPONSE trial, 222 phlebotomy-dependent patients with splenomegaly (> 450 cm3) and hydroxyurea resistance/intolerance were randomized 1:1 to receive Jakafi (10 mg bid; n=110) or best available therapy (n=112). The primary endpoint was the proportion of patients who achieved both hematocrit control without phlebotomy from week 8 to 32 (with ≤ 1 phlebotomy from week 0 to 8) and a ≥ 35% reduction in spleen volume from baseline by MRI at week 32.  At the end of the trial, the primary endpoint was achieved in 21% of patients in the Jakafi group vs 1% of patients in the best available therapy group (P < .0001). More specifically, 60% of the patients in the Jakafi group and 20% in the best available therapy group achieved hematocrit control without phlebotomy and  38% of patients in the Jakafi group and 1% of best available therapy group achieved a ≥ 35% spleen volume reduction. During the first 32 weeks, grade 3/4 anemia or thrombocytopenia occurred in 1.8% and 5.5% of jakafi-treated patients vs 0% and 3.6% of best available therapy patients.  Thromboembolic events occurred in 1 Jakafi-treated patient and 6 best available therapy patients.


The Prescription Drug User Fee Act (PDUFA) date for the sNDA for Jakafi is set for December 5, 2014.


Verstovsek S, Kiladjian J-J, Griesshammer M, et al. Results of a prospective, randomized, open-label phase 3 study of ruxolitinib (RUX) in polycythemia vera (PV) patients resistant to or intolerant of hydroxyurea (HU): the RESPONSE trial. J Clin Oncol 2014;32:5s (suppl; abstr 7026).

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