Study of Jakavi (ruxolitinib) met primary endpoint, improving two key measures of disease control in patients with polycythemia vera
Polycythemia vera is a chronic, incurable blood cancer with limited treatment options
Ruxolitinib is the first selective JAK 1/2 inhibitor to demonstrate efficacy in a Phase III trial for treating polycythemia vera
Data will be presented at an upcoming medical congress and submitted to worldwide regulatory authorities this year
Basel, March 7, 2014 - Novartis today announced that a pivotal Phase III trial of Jakavi® (ruxolitinib) compared to best available therapy has met its primary endpoint of maintaining hematocrit control (red blood cell volume) without the need for phlebotomy (a procedure to remove blood from the body to reduce the concentration of red blood cells) and reducing spleen size in patients with polycythemia vera resistant to or intolerant of hydroxyurea. The safety profile of ruxolitinib was generally consistent with previous studies based on initial review of the data.
Data from the study (RESPONSE) will be presented at an upcoming medical congress and submitted to worldwide regulatory authorities this year.
"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 ad interim and Global Head, Oncology Development and Medical Affairs. "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."
Polycythemia vera is a chronic, incurable blood cancer associated with an overproduction of blood cells. This leads to a thickening of the blood and increased risk of blood clots. These clots can cause serious cardiovascular complications, such as stroke and heart attack, resulting in increased morbidity and mortality. Patients with polycythemia vera often have enlarged spleen and additional debilitating symptoms. Many patients treated with commonly available therapies become intolerant or resistant, which is associated with an increased of risk of progression,.
RESPONSE is a global, randomized, open-label study conducted at 109 sites. The trial randomized 222 patients with polycythemia vera resistant to or intolerant of hydroxyurea. 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 is the proportion of patients whose hematocrit is controlled without phlebotomy and whose spleen volume is 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.
Ruxolitinibis currently approved in more than 55 countries for patients with myelofibrosis, a debilitating and life-threatening blood cancer.
Jakavi (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases and was approved by the European Commission in August 2012 for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. Jakavi is approved in more than 55 countries, including the European Union, Canada and some countries in Asia, Latin and South America. Additional worldwide regulatory filings are underway.
Novartis licensed ruxolitinib from Incyte Corporation for development and commercialization outside the United States. Both the European Commission and the U.S. Food and Drug Administration (FDA) granted ruxolitinib orphan drug status for myelofibrosis. Jakavi is marketed in the United States by Incyte Corporation under the name Jakafi® for the treatment of patients with intermediate or high-risk myelofibrosis.
The recommended starting dose for Jakavi in patients with myelofibrosis is 15 mg twice daily for patients with a platelet count between 100,000cubic millimeters (mm3) and 200,000 mm3,and 20 mg twice daily for patients with a platelet count of >200,000 mm3. Doses may be titrated based on safety and efficacy. There is limited information to recommend a starting dose for patients with platelet counts between 50,000/mm3 and <100,000/mm3. The maximum recommended starting dose in these patients is 5 mg twice daily, and patients should be titrated cautiously.
Jakavi is a registered trademark of Novartis AG in countries outside the United States. Jakafi is a registered trademark of Incyte Corporation.
The safety and efficacy profile of Jakavi has not yet been established outside the approved indication.
Jakavi Important Safety Information for Treatment of Myelofibrosis
Jakavi can cause serious side effects, including a decrease in blood cell count and infections. Complete blood count monitoring is recommended. Dose reduction or interruption may be required in patients with any hepatic impairment or severe renal impairment or in patients developing hematologic adverse reactions such as thrombocytopenia, anemia and neutropenia. Dose reductions are also recommended when Jakavi is co-administered with strong CYP3A4 inhibitors or fluconazole. Use of Jakavi during pregnancy is not recommended, and women should avoid becoming pregnant during Jakavi therapy. Women taking Jakavi should not breast feed.
The most common adverse drug reactions, occurring at any level of severity (incidence >10%) are urinary tract infections, anemia, thrombocytopenia, neutropenia, hypercholesterolemia, dizziness, headache, alanine aminotransaminase increased, asparte aminotransferase increased and bruising. Other common adverse drug reactions (incidence 1 to 10%) are herpes zoster, weight gain, flatulence and tuberculosis (1%). Progressive multifocal leukencephalopathy (PML) has been reported. Physicians should be alert for neuropsychiatric symptoms suggestive of PML.
Please see full Prescribing Information available at www.jakavi.com.
The foregoing release contains forward-looking statements that can be identified by words such as "will," "upcoming," "this year," "encouraged," "potential," "plan," "seek," "leads to," "can," "underway," "should," "has not yet," or similar terms, or by express or implied discussions regarding potential new indications or labeling for Jakavi, or regarding potential future revenues from Jakavi. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that Jakavi will be submitted or approved for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that Jakavi will be commercially successful in the future. In particular, management's expectations regarding Jakavi could be affected by, among other things, the uncertainties inherent in research and development, including unexpected clinical trial results and additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain proprietary intellectual property protection; general economic and industry conditions; global trends toward health care cost containment, including ongoing pricing pressures; unexpected manufacturing issues, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2013, the Group achieved net sales of USD 57.9 billion, while R&D throughout the Group amounted to approximately USD 9.9 billion (USD 9.6 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 136,000 full-time-equivalent associates and operate in more than 140 countries around the world.
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 Leukemia & Lymphoma Society. Polycythemia Vera Facts. June 2012. Available athttp://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/polycythemiavera.pdf.
 Finazzi G and Barbui T. How I treat patients with polycythemia vera. Blood. 2007;109(12):5104-5111.
 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.
 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.
 JAKAVI [Summary of Product Characteristics]. Basel, Switzerland: Novartis Pharma AG; 2012.
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