Safety and efficacy benefit of (Pr)Jakavi™ shown in clinical trial of over 1,000 patients with myelofibrosis

• Data from ongoing JAK Inhibitor Ruxolitinib in Myleofibrosis Patients (JUMP) trial supports the safety profile of Jakavi^TM (ruxolitinib) as seen in previous Phase III studies¹
  
  
• Patients on Jakavi^TM experienced a reduction in spleen size that was maintained over time and a clinically meaningful improvement in symptoms¹
  
  
• Jakavi^TM is the only JAK inhibitor approved in Canada for patients with myelofibrosis, an uncommon blood cancer ²

DORVAL, QC, Dec. 12, 2014 /CNW/ - Results from the JAK Inhibitor Ruxolitinib in Myleofibrosis Patients (JUMP) study, the largest clinical trial of myelofibrosis patients treated with Jakavi^TM (ruxolitinib) support the safety profile and efficacy benefit as measured in primary and secondary endpoints respectively.¹ In an analysis of 1,144 patients treated with Jakavi^TM to date in this ongoing expanded access study, 69 per cent of patients achieved a 50 per cent or greater reduction in spleen size from baseline and patients also experienced a clinical improvement in myelofibrosis symptom score, important treatment goals for patients with myelofibrosis.^1,3

Results from the JUMP study were presented at the 56th Annual Meeting of the American Society of Hematology (ASH) in San Francisco, California, on December 8, 2014.

In Canada, Jakavi^TM 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.⁷ The safety and efficacy data for Jakavi^TM from the JUMP trial, that were presented as new clinical information, are still under investigation, and are not in the current Canadian approved Jakavi^TM product monograph.

"The JUMP study results provide further data that support the safety and efficacy profile of ruxolitinib in myelofibrosis patients. It is encouraging to see the results of pivotal trials being reproduced in a large number of patients in an international study involving many countries. Long-term safety and efficacy of ruxolitinib justify the inclusion of ruxolitinib in routine clinical care in appropriate patients," said Dr. Vikas Gupta, President of the Canadian MPN Group, and site lead for the Elizabeth and Tony Comper MPN Program at Princess Margaret Cancer Centre in Toronto "Such results demonstrate the positive impact on symptoms and quality of life that treatment can have on patients with this blood cancer."  

"Patients with myelofibrosis often seek new data about available therapies that can help them manage the impact of this very serious disease," said Cheryl Petruk, Chairperson of the Canadian Myeloproliferative Neoplasms (MPN) Network. "These encouraging results from this large, international study of ruxolitinib provide additional hope that treatment can make an important difference in patients' lives."

About the JUMP Study
The JUMP study is a Phase IIIb, expanded-access trial for countries with no access to Jakavi™ outside of a clinical trial. The open-label, multicentre study analyzed 1,144 enrolled myelofibrosis patients who received daily starting doses of either 5 mg, 15 mg or 20 mg of Jakavi™ twice daily based on platelet counts at baseline. The primary endpoint is assessment of safety and tolerability of Jakavi™. Additional analyses included changes in spleen size and symptom scores as measured by the FACT-Lymphoma Total Score (FACT-Lym TS). As of September 22, 2014, 2,138 patients were enrolled at more than 200 study sites in 25 countries, and the final analysis will be performed after all patients have completed 24 months of treatment or ended treatment as part of the trial due to commercial availability.¹

Overall, the safety and efficacy profile of Jakavi™ was consistent with previous studies.^1,4,5 The most common Grade 3 or 4 hematologic adverse events (AEs) were anemia (33.0%) and thrombocytopenia (12.5%); however, they rarely led to discontinuation (2.6% of discontinuation was due to anemia and 3.2% of discontinuation was due to thrombocytopenia).¹ The most common nonhematologic AEs were diarrhea (14.5%), fever (13.3%), fatigue (12.9%) and asthenia (12.5%), which were primarily Grade 1 or 2.¹

About Myelofibrosis
Myelofibrosis is a rare, life-threatening blood cancer, with approximately 1 in every 133,000 people estimated to be affected by the disease.^2,8,9 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 as well as other severe complications and debilitating symptoms.^2,10  Myelofibrosis is typically diagnosed in people between 50 and 80 years old, although the disease can arise at any age, and can affect both men and women.⁶

Studies show that patients with myelofibrosis have a decreased life expectancy, with a median overall survival of 5.7 years.¹¹ 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 procedure.¹²

About Jakavi^TM  
Jakavi^TM (ruxolitinib), an antineoplastic agent, 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.⁷

Important Safety Information
Jakavi^TM 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^TM is co-administered with strong CYP3A4 inhibitors or fluconazole. Patients receiving Jakavi^TM should be monitored for pulse rate and blood pressure. Use of Jakavi^TM 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.¹³ For additional product information, please refer to the Jakavi^TM Canadian product monograph.

Disclaimer
This press release contains expressed or implied forward-looking statements, including statements that can be identified by terminology such as "can," "hope," "commitment," "goal," "will," or similar expressions. Such forward-looking statements reflect the current views of the Group regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results expressed or implied by such statements. These expectations could be affected by, among other things, risks and factors referred to in the Risk Factors section of 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 it in the future.

About Novartis Pharmaceuticals Canada Inc.
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 2013, 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.

About Novartis
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, 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 133,000 full-time-equivalent associates and sell products in more than 150 countries around the world. For more information, please visit www.novartis.com.

^TMJakavi is a trademark

References
1.	Martino B, Coutre P, Griesshammer, et al. Safety and Efficacy of Ruxolitinib in an Open-Label, Multicenter, Single-Arm, Expanded-Access Study in Patients with Myelofibrosis (MF): An 1144-Patient Update. Abstract #3197. 2014 American Society of Hematology (ASH) Annual Meeting, San Francisco, CA.
2.	Leukemia & Lymphoma Society. "Myelofibrosis Facts." Available at: http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/idiopathicmyelofibrosis.pdf. Accessed November 2014.
3.	Mesa RA. How I Treat Symptomatic Splenomegaly in Patients with Myelofibrosis. Blood. 2009;113(22):5394-5400.
4.	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.
5.	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.
6.	Leukemia & Lymphoma Society of Canada. Incidence: Idiopathic myelofibrosis. Available at: http://www.llscanada.org/#/diseaseinformation/myeloproliferativediseases/incidence/. Accessed December 2014.
7.	Novartis Pharmaceuticals Canada, Canadian Product Monograph for Jakavi (ruxolitinib), dated November 25, 2014.
8.	Girodon F, Bonicelli G, Schaeffer C, et al. Significant Increase in the Apparent Incidence of Essential Thrombocythemia Related to New Who Diagnostic Criteria: A Population-Based Study. Haematologica. 2009; 94(6):865-869.
9.	McNally RJQ, Rowland D, Roman E, Cartwright RA. Age and Sex Distributions of Hematological Malignancies in the U.K. Hematol Oncol. 1997;15:173–189.
10.	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.
11.	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.
12.	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.

Novartis Media Relations: Andrea Gilpin, Novartis Pharmaceuticals Canada Inc., + 1 514-633-7873, [email protected]