Novartis Drug PrJakavi® Associated with Significant Clinical Benefit for Patients with Debilitating and Life-threatening Blood Cancer Myelofibrosis

Analyses of Phase III data provided evidence of sustained spleen reduction and quality of life improvements

DORVAL, QC, March 7, 2014 /CNW/ - Study results presented at the 55th American Society of Hematology (ASH) annual meeting showed that patients with myelofibrosis who received treatment with Jakavi^® (ruxolitinib) sustained reductions in spleen volume and sustained improvements in quality of life after three years of treatment. These results were demonstrated in analyses from the Phase III COMFORT-I (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy) study. These long-term follow up results build on previously established data and reinforce the sustained efficacy and long-term safety profile of Jakavi^® in patients with myelofibrosis.

Of the patients treated with Jakavi^® 59% experienced at least a 35% reduction in spleen size at any time during the three year study. In an exploratory analysis, patients who continued on therapy experienced sustained improvements in the Global Health Status/Quality of Life and the functional domains of the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30). Median follow-up was 149 weeks at the time of the updated analysis.

This scientific data was presented at ASH as new clinical information regarding Jakavi^® and is not contained in the current Canadian approved product monograph. Jakavi^® is indicated for the treatment of splenomegaly and/or its associated symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), postpolycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis.¹

"The long-term results of the COMFORT-I study provided data supporting the safety and efficacy of ruxolitinib in myelofibrosis, and the benefit on quality of life is significant," said Dr. Vikas Gupta a myeloproliferative neoplasms specialist at the Princess Margaret Cancer Centre in Toronto. "Several novel agents are on the horizon in the treatment of myelofibrosis, and we are entering an era of renewed hope for myelofibrosis patients."

Latest Presented COMFORT Data
The COMFORT-I study is part of the largest clinical trial program in myelofibrosis to date. Further analyses of phase III data were presented at the 2013 ASH annual meeting early in December. Jakavi^® continues to reduce risk of deaths for patients with myelofibrosis as reported in the following abstracts:

• Impact of Prognostically Detrimental Mutations in COMFORT-II (abstract #107)².
• Three-Year Update From COMFORT-I Study (abstract #396)³.
• A Pooled Overall Survival Analysis of the COMFORT Studies (abstract #2820)⁴.
• A Retrospective Comparison of the DIPSS and COMFORT-II Study (abstract #4066)⁵.

For full study details please go to: http://www.hematology.org/Meetings/Annual-Meeting/Abstracts/5810.aspx

COMFORT Studies Background
The COMFORT (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy) studies are randomized, Phase III studies comparing the safety and efficacy of Jakavi^® with placebo or best available treatment (BAT) in patients with intermediate-2- or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis. COMFORT-I is a double-blind study whereas COMFORT-II is open label. Patients initially received Jakavi^® 15 or 20 mg twice daily based on their platelet counts at baseline (100-200 and > 200 x 10⁹/L, respectively) and were individually titrated to maximize safety and efficacy. Patients were allowed to cross over from the control arms of each study upon protocol-defined progression events (primarily progressive splenomegaly, defined as a ≥ 25% increase in spleen volume from baseline or on-study nadir in COMFORT-I and -II, respectively). At the time of the analysis reported at the 2013 American Society of Hematology annual meeting, all ongoing control patients had crossed over to Jakavi^®. Overall survival was a secondary endpoint in both studies⁴.

About Myelofibrosis
Myelofibrosis is a life-threatening blood cancer with a poor prognosis and limited treatment options⁶. Myelofibrosis develops when uncontrolled signaling in the JAK pathway - which regulates blood cell production - causes the body to make blood cells that do not work properly, which scars the bone marrow and results in an enlarged spleen and other severe complications⁷. Although the exact prevalence is uncertain, a recent analysis done in the United States estimates myelofibrosis prevalence ranged from 3.6-5.7 per 100,000 patients⁸. Myelofibrosis is typically diagnosed in people between 50 and 80 years old, although the disease can arise at any age.  Both men and women are affected⁹.

Studies showed that patients with myelofibrosis have a decreased life expectancy, with a median overall survival of 5.7 years¹⁰. Although allogeneic stem cell transplantation may cure myelofibrosis, the procedure is associated with significant morbidity and transplant-related mortality, and is available to less than 5% of patients who are young and fit enough to undergo the procedure¹¹.

About Jakavi^® (ruxolitinib)
Jakavi^® (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases approved by Health Canada in July 2012 for the treatment of splenomegaly (enlarged spleen) and/or its associated symptoms in adult patients with myelofibrosis.

Important Safety Information
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 severe hepatic or 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. Patients receiving Jakavi^® should be monitored for pulse rate and blood pressure. 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, bruising, bleeding and increased blood pressure. Other common adverse drug reactions (incidence 1 to 10%) are herpes zoster, weight gain, flatulence and tuberculosis (1%). In the post-marketing setting, Progressive multifocal leukencephalopathy (PML) has been reported. Physicians should be alert for neuropsychiatric symptoms suggestive of PML¹. For additional product information, please refer to the Jakavi^® Canadian product monograph.

About Novartis
Novartis Pharmaceuticals Canada Inc., a leader in the healthcare field, is committed to the discovery, development and marketing of innovative products to improve the well-being of all Canadians. In 2012, the company invested close to $100 million in research and development in Canada. Novartis Pharmaceuticals Canada Inc. employs more than 600 people in Canada. For further information, please consult www.novartis.ca.

Novartis Pharmaceuticals Canada Inc. is a subsidiary of Novartis AG, which provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis Group of Companies 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.

For more information, please visit http://www.novartis.com.

^®Jakavi is a registered trademark

References
_________________________

¹ Product Monograph, Jakavi (ruxolitinib) Novartis Pharmaceuticals Canada Inc., revised August 14, 2013. Available at: http://novartis.ca/products/en/pharmaceuticals-j.shtml
² Guglielmelli P, Biamonte F, Pieri L, et al. Impact of Prognostically Detrimental Mutations (ASXL1, EZH2, SRSF2, IDH1/2) on Outcomes in Patients With Myelofibrosis Treated With Ruxolitinib in COMFORT-II. Abstract #107.55th American Society of Hematology (ASH) Annual Meeting and Exposition, 2013. New Orleans, LA.
³ 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.
⁴ Vannucchi A, Hagpop K, Kiladjian JJ, et al. A Pooled Overall Survival Analysis of the COMFORT Studies: 2 Randomized Phase 3 Trials of Ruxolitinib for the Treatment of Myelofibrosis. Abstract #2820.55th American Society of Hematology (ASH) Annual Meeting and Exposition, 2013. New Orleans, LA.
⁵ Passamonti F, Maffioli M, Cervantes F, et al. Impact of Ruxolitinib on the Natural History of Patients with Primary Myelofibrosis: A Retrospective Comparison of the DIPSS and the COMFORT-II Cohorts. Abstract#4066. 55th American Society of Hematology (ASH) Annual Meeting and Exposition, 2013. New Orleans, LA.
⁶ Gangat N, Caramazza D, Vaidya R, et al. DIPSS-plus: A refined Dynamic International Prognostic Scoring System (DIPSS) for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count and transfusion status. J Clin Oncol. 2011; 29:392-397.
⁷ Mesa RA, Schwagera S, Radia D, et al. The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leuk Res. 2009;33:1199-1203.
⁸ MPN Foundation. Prevalence (MF) Available at: http://www.mpnresearchfoundation.org/Prevalence Accessed December 2013
⁹ Leukemia & Lymphoma Society of Canada. Incidence: Idiopathic myelofibrosis. Available at: http://www.llscanada.org/#/diseaseinformation/myeloproliferativediseases/incidence/. Accessed December 2013.
¹⁰ Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009;113:2895-2901.
¹¹ Patriarca F, Bacigalupo A, Sperotto A, et al. Allogeneic hematopoietic stem cell transplantation in myelofibrosis: the 20-year experience of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Haematologica. 2008;93(10):1514-1522.

SOURCE: Novartis Pharmaceuticals Canada Inc.

For further information:

Novartis Media Relations:
Andrea Gilpin
Novartis Pharma Communications
[phone]
[email protected]