Health Canada approves PrJakavi® (ruxolitinib) for polycythemia vera, a chronic blood cancer(1)

• Approval based on pivotal Phase III RESPONSE trial that showed patients achieved hematocrit control without phlebotomy²

DORVAL, QC, Feb. 18, 2016 /CNW/ - Health Canada has approved Jakavi^® (ruxolitinib), for the control of hematocrit in adult patients with polycythemia vera (PV) resistant to or intolerant of a cytoreductive agent. Jakavi^® is the first targeted treatment approved for this type of blood cancer, a myeloproliferative neoplasm (MPN). PV is an incurable condition that causes an over-production of blood cells.³ Without treatment to slow down the production of blood cells, PV can lead to serious complications such as heart failure, heart attack and stroke.³

"Some patients with PV become resistant or intolerant to a cytoreductive therapy. There are no standard treatments for these patients, and this is an area of unmet clinical need," said Dr. Vikas Gupta, Director of the Elizabeth and Tony Comper MPN Program at the Princess Margaret Cancer Centre in Toronto and President of the Canadian MPN Group. "This approval is good news for patients with PV and extends the role of ruxolitinib in the management of MPNs."

"PV patients have been waiting a long time for a new treatment option. The approval of Jakavi^® in the PV setting in Canada is a step forward in the right direction for patients.  We look forward to this new treatment being made available to patients through provincial drug plans as quickly as possible," said Cheryl Petruk, President of MPN Network of Canada, a group supporting Canadians with PV and other myeloproliferative neoplasms (MPNs), a group of blood cancers that originate in the bone marrow where blood cells are created.⁴

About the RESPONSE study
The approval of Jakavi^® is based on clinical efficacy in patients with polycythemia vera demonstrated in a Phase III study (RESPONSE) versus best available therapy (BAT).  A higher proportion of patients in the Jakavi^® group achieved the primary composite endpoint and each of its individual components. Significantly more patients in the Jakavi^® group (20.9%) compared to the BAT group (0.9%) achieved the primary composite endpoint (p<0.0001). Hematocrit control was achieved in 60% of patients in the Jakavi^® group compared to 19.6% in the BAT group and ≥ 35% reduction in spleen volume was achieved in 38.2% of patients in the Jakavi^® group compared to 0.9% in the BAT group.²

Both key secondary endpoints were also met: The proportion of patients achieving a complete hematologic remission at week 32 was 23.6% in the Jakavi^® group compared to 8.9% in the BAT group (p=0.0028), and the proportion of patients achieving a durable primary response at week 48 was 19.1% in the Jakavi^® group and 0.9% in the BAT group (p<0.0001), which represent 91.3% (n=21/n=23) of patients in the Jakavi^®  group who achieved the primary endpoint at week 32 and maintained it at week 48.²

About polycythemia vera (PV)
Polycythemia vera (PV) is an incurable blood cancer associated with an overproduction of blood cells in the bone marrow.⁴ PV affects roughly 47 to 57 people per 100,000 in the United States⁵ which is approximately 17,000 to 20,000 people in Canada.⁶ The disease is driven by the dysregulation of the JAK-STAT pathway⁷ and is typically characterized by elevated hematocrit, the volume percentage of red blood cells in whole blood, which can lead to a thickening of the blood and an increased risk of blood clots, as well as an elevated white blood cell and platelet count.⁴ If left untreated, this can cause serious cardiovascular complications, such as stroke and heart attack,³ resulting in increased morbidity and mortality.⁸ Patients with PV may have an enlarged spleen and symptoms that are frequent and burdensome, and can develop myelofibrosis.³

About Jakavi^®
The Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway regulates blood cell production and is known to play a key role in the underlying mechanism of PV.⁷ Jakavi^® specifically targets the JAK-STAT pathway. The recommended starting dose of Jakavi^® in PV is based on platelet count and is 10 mg given orally twice daily for counts greater than 200,000/mm³ and 5 mg given orally twice daily for platelet counts between 50,000 and <100,000/mm³ ; doses may be titrated based on safety and efficacy.² Jakavi^® is also approved in Canada for the treatment of splenomegaly and/or its associated symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. It is available in four strengths; 5 mg, 10 mg, 15 mg and 20 mg tablets.² Jakavi^® is approved in more than 80 countries for patients with myelofibrosis and in the European Union for PV.⁹

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 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 moderate CYP3A4 and CYP2C9 inhibitors. Rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption. Patients receiving Jakavi^® should be monitored for non-melanoma skin cancer, pulse rate, blood pressure and hemorrhage. Use of Jakavi^® during use of contraception in women of childbearing potential, pregnancy is not recommended, and women should avoid becoming pregnant during Jakavi^® therapy. Women taking Jakavi^® should not breast feed. Appropriate precautions from male patients should be taken to avoid fathering a patient during treatment.

The most frequently reported hematological adverse reactions in patients with polycythemia vera (any CTCAE grade, N=110 patients from Jakavi^® arm of RESPONSE) included anemia (43.6%) and thrombocytopenia (24.5%).  The four most frequent non-hematologic adverse reactions reported at a higher frequency in the Jakavi^® group than in the BAT group were diarrhea (14.5%), muscle spasm (11.8%), dizziness (11.8%) and dyspnea (10.0%) respectively. The most frequent non-hematological laboratory abnormalities (any CTCAE grade) in the Jakavi^® group were hypercholesterolemia (30.0%), gamma glutamyl transferase (Hyper) (29.1%), bicarbonate (Hypo) (28.2%), lipase (Hyper) (28.2%), raised alanine aminotransferase (22.7%), glucose (Hypo) (22.7%), and raised aspartate aminotransferase (20.9%) respectively. For additional product information, please refer to the Jakavi^® Canadian Product Monograph.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as "hope," "will," "as soon as possible," "expected," or similar terms, or by express or implied discussions regarding potential additional marketing approvals or 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. Neither can there be any guarantee that Jakavi^® will be submitted or approved for sale in any additional markets or at any particular time. Nor can there be any guarantee that Jakavi^® will be commercially successful in the future, or will achieve any particular level of revenue. 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 and reimbursement issues; unexpected safety issues; 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.

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. Novartis Pharmaceuticals Canada Inc. employs approximately 700 people in Canada. For further information, please consult www.novartis.ca.

Located in Dorval, Quebec, Novartis Pharmaceuticals Canada Inc. is an affiliate of Novartis AG, which 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 and cost-saving generic pharmaceuticals. Novartis is the only global company with leading positions in these areas. In 2014, the Group achieved net sales of USD 58.0 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 120,000 full-time equivalent associates. Novartis products are available in more than 180 countries around the world. For more information, please visit http://www.novartis.com.

Jakavi is a registered trademark of Novartis Pharmaceuticals Canada Inc.

References:

¹ MPN Research Foundation, Polycythemia Vera (PV), What is PV? Accessed February 5, 2016 at: http://www.mpnresearchfoundation.org/Polycythemia-Vera--28PV-29

² Novartis Pharmaceuticals Canada Inc., JAKAVI (ruxolitinib tablets) Product Monograph, November 23, 2015, pp 35-37, page 20, page 3.

³ National Heart, Lung and Blood Institute, U.S. Department of Health & Human Services. What Is Polycythemia Vera? Accessed February 5, 2016 at: http://www.nhlbi.nih.gov/health/health-topics/topics/poly/

⁴ Leukemia & Lymphoma Society. Polycythemia Vera Facts. Available at: http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/polycythemiavera.pdf. Accessed on February 5, 2016.

⁵ Mehta J, Wang H, Iqbal SU, Mesa R. Epidemiology of myeloproliferative neoplasms in the United States. Leuk Lymphoma. 2014 Mar; 55(3):595-600. Accessed February 5, 2016 at: http://www.ncbi.nlm.nih.gov/pubmed/23768070

⁶ Statistics Canada, Canada's population estimates, first quarter 2015. Accessed February 5, 2016 at: http://www.statcan.gc.ca/daily-quotidien/150617/dq150617c-eng.htm

⁷ Schafer AI. Molecular Basis of the Diagnosis and Treatment of Polycythemia Vera and Essential Thrombocythemia. Blood. 2006; 107(11):4214-4222.

⁸ Finazzi G and Barbui T. How I Treat Patients with Polycythemia Vera. Blood. 2007; 109(12):5104-5111.

⁹ Novartis International AG, Press Release, Novartis receives EU approval for Jakavi^® in polycythemia vera, first targeted therapy approved for patients with this rare blood cancer, March 17, 2015. Accessed February 5, 2016, at: https://www.novartis.com/news/media-releases/novartis-receives-eu-approval-jakavi%C2%AE-polycythemia-vera-first-targeted-therapy

SOURCE Novartis Pharmaceuticals Canada Inc.

Novartis Media Relations: Daphne Weatherby, Novartis Pharma Communications, [phone], [email protected], [phone], [email protected]