(PR)JAKAVI® the first medication to receive Health Canada approval to treat patients with myelofibrosis

• Myelofibrosis is a life-threatening blood cancer associated with progressive, debilitating symptoms that can severely impact quality of life and shorten survival
• ^PRJAKAVI^® (ruxolitinib tablets) approval is based on results from the most extensive myelofibrosis clinical trial program to-date

DORVAL, QC, July 5, 2012 /CNW/ - Novartis Pharmaceuticals Canada Inc. (Novartis) has received approval from Health Canada for JAKAVI (ruxolitinib tablets), a drug for the treatment of disease-related splenomegaly (enlarged spleen) and/or its associated symptoms in adult patients with myelofibrosis (MF), a blood cancer.¹ JAKAVI is the first antineoplastic agent indicated for this patient population.

Given the unmet medical need in this area, the JAKAVI submission was reviewed under a priority review status by Health Canada. JAKAVI represents the only approved JAK 1 and JAK 2 inhibitor for the treatment of splenomegaly and/or its associated symptoms in adult patients with MF in Canada. Until now, there have been no Health Canada approved treatments for these patients.

"JAKAVI offers an option to patients who suffer from myelofibrosis. It can improve some of the more serious and debilitating complications of this disease by shrinking their enlarged spleen," says Dr. Vikas Gupta, Associate Professor and Clinical Investigator, Leukemia Program at Princess Margaret Cancer Centre, Toronto. "Day-to-day living improves: patients become more active, their pain diminishes, sleep improves and they regain their appetite, which allows for an improved quality of life."

Myelofibrosis is a rare, life-threatening blood cancer affecting the bone marrow and is characterized by bone marrow scarring (fibrosis), an enlarged spleen (splenomegaly) and debilitating consequences, including fatigue, fever, night sweats, itchy skin, bone pain, abdominal pain or discomfort, and weight loss.^2,3 Prognosis for patients with MF is poor, with a median survival of approximately five-to-six years, and limited treatment options.^4,5,6

When Dave Galley, an Ottawa engineer, wasn't feeling well, he went to the doctor expecting to be told he had a persistent case of the flu; however, approximately six weeks later, and following a number of misdiagnoses, the 50 year-old man was told he had MF. Dave instantly felt scared as he had never heard about MF, but was determined to be strong - he knew he had to live each day to the fullest because he didn't know how much time he had left with his wife and two sons.

"As a husband and father of two teenage boys, the news of a cancer diagnosis was gut-wrenching," says Dave Galley, a person living with MF. "I was overcome with emotion and my life instantly changed at that moment. Fortunately, my doctor put me in a clinical trial for a new therapy called JAKAVI. I have been taking JAKAVI pills for two years now, and for the first time, the disease is not the first thing on my mind."

"We applaud Health Canada's rapid approval of this important treatment and we look forward to a timely, positive recommendation from the panCanandian Oncology Drug Review so JAKAVI can be available to all Canadians with myelofibrosis," says Durhane Wong-Rieger, President of the Canadian Organization for Rare Disorders.

Largest Clinical Program in MF

Health Canada's approval of JAKAVI is based on results from the largest clinical program conducted in MF called COMFORT (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy),^7,8 with Canadian centres in Vancouver, London, Toronto, Ottawa, Montreal, and St. John's (NFLD).

The New England Journal of Medicine recently published results from two Phase III trials which found that treatment with Janus kinase (JAK) inhibitor - JAKAVI, reduced disease burden in patients with MF. ^9,10 In the first Phase III trial, results from COMFORT-I show JAKAVI provides statistically significant clinical improvement in patients with MF at just 24 weeks as measured by spleen volume reduction and symptom improvement compared to placebo.¹¹ Results were first presented at the 47th American Society of Clinical Oncology (ASCO) annual meeting in June 2011.¹²

In the second Phase III trial, COMFORT-II, data show JAKAVI provides marked and durable clinical improvement in patients with MF, measured by reduction in spleen volume at 48 weeks and 24 weeks compared to best available therapy.¹³

JAKAVI is available in three strengths: 5 mg, 15 mg and 20 mg tablets taken orally twice daily. For the dosage and administration of JAKAVI, please refer to the approved JAKAVI Product Monograph dated June 15, 2012.

About Myelofibrosis (MF)

In Canada, MF is estimated to affect about two out of every 1,000,000 people,¹⁴ although the exact prevalence is uncertain and depends on the population sampled. The spleen of a person with MF can grow to ten times normal size, causing discomfort in the stomach or shoulder pain.^15,16,17 Serious complications of the disease severely impact the quality of life of people with MF and shorten survival.^18,19

MF is typically diagnosed between ages 50 to 80 years, but can occur at any age.²⁰ Both men and women are affected.²¹ A physician may consider a diagnosis of MF when a routine medical examination shows an enlarged spleen (found in almost all patients) and abnormal levels of red blood cells, white blood cells and platelets.²² Diagnosis is usually determined by a bone marrow aspiration and biopsy.²³

Effective treatments for patients with MF are needed, which is why JAKAVI received a priority review status from Health Canada. Novartis is working with federal, provincial and territorial authorities to ensure patients in Canada have access to JAKAVI through provincial and private drug plans.

About JAKAVI

JAKAVI offers a unique mechanism of action that targets what studies suggest is the underlying pathology of the disease, rather than using medications developed for treatment of other conditions that have limited effectiveness. A potent and selective dual oral JAK 1 and JAK 2 inhibitor, JAKAVI is designed to specifically inhibit the biological activity of these JAK enzymes for the treatment of this patient population with MF.

JAKAVI is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. The overall safety profile of JAKAVI is consistent across all clinical studies.^24,25 JAKAVI was generally well-tolerated with manageable and predictable side effects.^26,27,28 The most frequently reported hematological adverse reactions (any CTCAE; grade N=301 patients from ruxolitinib arms of COMFORT-I and COMFORT-II) included reversible thrombocytopenia (69.8%) (an abnormal drop in the number of blood cells involved in forming blood clots), anemia (82.4%) (the condition of having less than the normal amount of red blood cells or hemoglobin in the blood) and neutropenia (15.6%) (an abnormally low level of neutrophils in the blood. Neutrophils are white blood cells produced in the bone marrow that ingest bacteria).²⁹ The three most frequent non-hematological adverse reactions were bruising (21.3%), dizziness (15.0%) and headache (13.6%).³⁰

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 2011, the company invested close to $100 million in research and development in Canada. Novartis Pharmaceuticals Canada Inc. employs more than 600 people in Canada. It was named for the seventh time as one of the "50 Best Employers in Canada" for 2011. For further information, please consult www.novartis.ca.

References:

^{_______________
1} JAKAVI Canadian approved Product Monograph, dated June 15, 2012.
² 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.
³ The Leukemia & Lymphoma Society. Idiopathic myelofibrosis. 2007. Available at http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/idiopathicmyelofibrosis.pdf. Accessed January 20, 2012.
⁴ Mesa RA, Schwager 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. Leukemia research. Sep 2009;33(9):1199-1203.
⁵ Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. The New England journal of medicine. Sep 16 2010;363(12):1117-1127.
⁶ 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. Mar 26 2009;113(13):2895-2901.
⁷ Verstovsek S, Mesa RA, Gotlib J, et al. A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis. New Eng J Med. 2012: March 1;366:799-807.
⁸ Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis. New Eng J Med. 2012: March 1;366:787-98.
⁹ Verstovsek S, Mesa RA, Gotlib J, et al. A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis. New Eng J Med. 2012: March 1;366:799-807.
¹⁰ Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis. New Eng J Med. 2012: March 1;366:787-98.
¹¹ Verstovsek S, Mesa RA, Gotlib J, et al. A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis. New Eng J Med. 2012: March 1;366:799-807.
¹² Verstovsek S, Mesa RA, Gotlib JR, et al. Results of COMFORT-I, a randomized double-blind phase III trial of JAK 1/2 inhibitor INCB18424 (424) versus placebo (PB) for patients with myelofibrosis (MF).  J Clin Oncol 29: 2011 (suppl; abstr 6500).
¹³ Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis. New Eng J Med. 2012: March 1;366:787-98.
¹⁴ The Leukemia & Lymphoma Society. Incidence. Updated March, 2011. Available at http://www.llscanada.org/#/diseaseinformation/myeloproliferativediseases/incidence/. Accessed June 4, 2012.
¹⁵ Mesa RA. How I treat symptomatic splenomegaly in patients with myelofibrosis. Blood. 2009;113(22):5394-5400.
¹⁶ Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and Efficacy of JAK1 & JAK2 Inhibitor, INCB018424, in Myelofibrosis. New Eng J Med. 2010;16(363):1117-1127.
¹⁷ Leukemia & Lymphoma Society. Idiopathic myelofibrosis. Available at: http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/idiopathicmyelofibrosis.pdf Accessed April 2011.
¹⁸ Mesa, R.A., 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(9): p. 1199-203.
¹⁹ The Leukemia & Lymphoma Society. Idiopathic myelofibrosis. 2007. Available at http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/idiopathicmyelofibrosis.pdf. Accessed January 20, 2012.
²⁰ The Leukemia & Lymphoma Society. Incidence. Updated March, 2011. Available at http://www.llscanada.org/#/diseaseinformation/myeloproliferativediseases/incidence/. Accessed June 4, 2012.
²¹ The Leukemia & Lymphoma Society. Incidence. Updated March, 2011. Available at http://www.llscanada.org/#/diseaseinformation/myeloproliferativediseases/incidence/. Accessed June 4, 2012.
²² Leukemia & Lymphoma Society. Idiopathic myelofibrosis. Available at: http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/idiopathicmyelofibrosis.pdf Accessed June 2011.
²³ Leukemia & Lymphoma Society. Idiopathic myelofibrosis. Available at: http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/idiopathicmyelofibrosis.pdf Accessed June 2011.
²⁴ Verstovsek S, Mesa RA, Gotlib J, et al. A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis. New Eng J Med. 2012: March 1;366:799-807.
²⁵ Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis. New Eng J Med. 2012: March 1;366:787-98.
²⁶ Verstovsek S, Mesa RA, Gotlib J, et al. A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis. New Eng J Med. 2012: March 1;366:799-807.
²⁷ Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis. New Eng J Med. 2012: March 1;366:787-98.
²⁸ Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and Efficacy of JAK1 & JAK2 Inhibitor, INCB018424, in Myelofibrosis. New Eng J Med. 2010 September 16;363:1117-1127.
²⁹ JAKAVI Canadian approved Product Monograph, dated June 15, 2012.
³⁰ JAKAVI Canadian approved Product Monograph, dated June 15, 2012.

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