Longer follow-up data of (Pr)Tasigna* confirms hope for patients with newly
diagnosed chronic myeloid leukemia

Tasigna continues to surpass gold standard in slowing disease progression and inducing deeper and more durable response

DORVAL, QC, Dec. 7 /CNW/ - Novartis announced today 24-month follow-up data showing that Tasigna* (nilotinib) continues to surpass ^PrGleevec* (imatinib) in the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase¹. These new data, from the first Phase III comparison of the two oral therapies as initial treatment for this blood cancer, were presented at the 52^nd Annual Meeting and Exposition of the American Society of Hematology (ASH) in Orlando, Florida.

CML is one of the four types of leukemia². It is caused by an abnormal chromosome, called the Philadelphia (Ph) chromosome which produces an abnormal cancer protein called Bcr-Abl, which is responsible for blocking the normal signal that tells the body to stop producing white blood cells. As a result, CML patients have a significantly elevated cancerous white blood cell count.

Without treatment, CML typically progresses over three to five years from the initial (chronic) phase through a transition period (accelerated phase) to a rapidly fatal form (blast crisis)³.

At 24 months, the Phase III randomized, open-label, multicenter clinical trial, named ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+ CML Patients), found that first-line treatment with Tasigna* at 300 mg twice daily resulted in a lower incidence of progression to accelerated phase and blast crisis, compared to the standard approved dose of Gleevec* 400 mg once daily. Patients receiving Tasigna* also had a lower incidence of suboptimal response and treatment failure as defined by study criteria¹. 

These data also showed that Tasigna* induced higher rates of complete cytogenetic response (CCyR) and major molecular response (MMR) compared to Gleevec*, as well as a significantly higher rate of an even deeper response - a trace amount of 0.0032% or less of the Bcr-Abl protein that causes Ph+ CML, which is considered a complete molecular response (CMR)¹. Remarkably, Tasigna* induced more durable MMR compared to Gleevec*. Fewer patients taking Tasigna* in the study discontinued treatment due to adverse events compared to Gleevec¹. Tasigna* and Gleevec* were generally well tolerated.

"We are encouraged by the ongoing clinical development of Tasigna* as a treatment for newly diagnosed patients with chronic phase Ph+ CML," says Dr. Jeffrey Lipton, a medical oncologist with Princess Margaret Hospital in Toronto, Ontario. "The 24-month data indicate that patients who begin their treatment with Tasigna* may have long-term improvement and progression-free survival."

Rates of MMR and CCyR remain statistically higher for Tasigna* versus Gleevec* at the 24-month minimum follow-up. MMR was achieved by 71% of patients taking Tasigna* 300 mg twice daily and 67% of patients taking Tasigna* 400 mg twice daily, compared to 44% of patients taking Gleevec* by 24 months. Durable MMR rates were statistically significantly higher in the Tasigna* 300 mg twice daily and Tasigna* 400 mg twice daily arms compared to Gleevec* 400 mg once daily (42%, 39% and 21% respectively). Significantly more patients achieved CCyR in the Tasigna* 300 mg and 400 mg arms compared to the Gleevec* arms at 87% and 85% vs. 77% respectively by 24 months.

Another study also presented at this year's annual ASH meeting provides further support for the use of Tasigna* in patients with newly diagnosed Ph+ CML. The Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) study, an ongoing, open-label, single-stage, multicenter Phase II clinical trial, was presented on Saturday, December 4, 2010⁴.

Study Details

ENESTnd, the largest global randomized comparison of two oral therapies ever conducted in newly diagnosed Ph+ CML patients, was conducted at 217 global sites with 846 patients enrolled. Patients were randomized to receive Tasigna* 300 mg twice daily (n = 282), Tasigna 400 mg twice daily (n = 281) or Gleevec* 400 mg once daily (n = 283). The primary endpoint was MMR at 12 months; the key secondary endpoint was durable MMR at 24 months (patients having MMR when evaluated at both 12 and 24 months)¹. MMR was defined in the study as reduction in the level of the abnormal Bcr-Abl gene to less than or equal to 0.1% of the pretreatment level based on an internationally agreed standard¹. Planned follow-up is for five years. Patients on the Gleevec* treatment arm who had suboptimal response or treatment failure were allowed to escalate dose and/or switch to Tasigna via a protocol extension. The data was presented at ASH is the 24-month minimum follow-up.

Results showed that fewer patients progressed to accelerated phase or blast crisis while on treatment with Tasigna* at 300 mg twice daily (n = 2) and 400 mg twice daily (n = 3) versus Gleevec* at 400 mg once daily (n = 12)¹ with 24 months of minimum follow-up, demonstrating a significant improvement in disease control.

The data also showed that nearly three times more patients taking Tasigna* 300 mg twice daily achieved CMR - defined as a trace amount of 0.0032% or less of the Bcr-Abl protein that causes Ph+ CML - with Tasigna* 300 mg twice daily (n = 70) than with Gleevec* (n = 25) by 24-months¹.

All patients had a minimum of 24 months of treatment or discontinued early; the median follow-up was 25 months. Overall, 75%, 78% and 68% of patients remained in the study on Tasigna* 300 mg twice daily, Tasigna* 400 mg twice daily and Gleevec* 400 mg once daily, respectively¹.

Both Tasigna* and Gleevec* were generally well tolerated overall. Rates of discontinuation due to adverse events or laboratory abnormalities were 9% for Tasigna* 300 mg twice daily, 11% for Tasigna* 400 mg twice daily and 13% for Gleevec* 400 mg once daily¹. No patients treated with Tasigna* in the study had prolongation of QT interval >500 milliseconds¹. No sudden deaths occurred in any of the treatment arms¹.

About Tasigna*

On September 9, 2008, Health Canada approved Tasigna* (nilotinib capsules) with conditions, for the treatment of accelerated-phase (AP) with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in adult patients resistant to or intolerant of at least one prior therapy including Gleevec* (imatinib mesylate). Tasigna* was specifically designed - based on the success of Gleevec* - to preferentially target Bcr-Abl, the key cause and driver of Ph+ CML.

Tasigna* Important Safety Information

Tasigna* prolongs the QT interval.  Uncommon sudden cardiac deaths have been reported in patients receiving Tasigna*. Tasigna* should not be used in patients with a known long QT prolongation or with a persistent QT of ＞480 msec. Tasigna* should not be used in patients with uncorrectable hypokalemia (low potassium levels), hypomagnesemia (low magnesium levels).  Hepatotoxicity/Hepatic failure and pancreatitis have been reported. Hypokalemia or hypomagnesemia must be corrected prior to Tasigna* administration and should be periodically monitored. Drugs known to prolong the QT interval and strong CYP3A4 inhibitors should be avoided. Tasigna* must not be taken with food since its absorption is increased if taken with food.

For additional information, please refer to the Tasigna* product monograph available at www.novartis.ca⁵.

Gleevec* Important Safety Information

The majority of patients treated with Gleevec* in clinical trials experienced adverse events at some time. Most events were of mild to moderate grade and treatment discontinuation was not necessary in the majority of cases.

For additional information, please refer to the Gleevec* product monograph www.novartis.ca⁶.

Disclaimer

The foregoing press release contains forward-looking statements that can be identified by forward-looking terminology, such as "to file", "may", "should", "potential", "promise", "plans", "will", or similar expressions, or by express or implied discussions regarding potential new indications or labelling for Tasigna* or regarding potential future revenues from Tasigna* or Gleevec*. You should not place undue reliance on these statements.  Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Tasigna* or Gleevec* to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Tasigna* will be approved for any additional indications or labeling in any market. Nor can there be any guarantee that Tasigna* or Gleevec* will achieve any particular levels of revenue in the future. In particular, management's expectations regarding Tasigna* and Gleevec* could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. 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. conducts hundreds of clinical trials across the country seeking new treatments for cardiovascular disease, oncology, diabetes, cancer, ophthalmology and organ transplantation. In 2009, the Company invested close to $110 million in research and development. Novartis Pharmaceuticals Canada Inc. employs more than 700 people in Canada and its headquarters are located in Dorval, Québec. In addition to Novartis Pharmaceuticals Canada Inc., the Novartis Group in Canada consists of Novartis Animal Health Canada Inc., Novartis Consumer Health Canada Inc., CIBA Vision Canada Inc. and Sandoz Canada Inc. For further information about Novartis Canada, please consult www.novartis.ca.

*Gleevec is a registered trademark.

*Tasigna is a registered trademark.

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¹ Hughes T, et al. ENESTnd Update: Continued Superiority of Nilotinib Versus Imatinib In Patients with Newly Diagnosed Chronic Myeloid Leukemia In Chronic Phase (CML-CP). 52nd Annual Meeting of the American Society of Hematology. Abstract No. 207. December 6, 2010.
² CML Society of Canada: Understanding CML - http://www.cmlsociety.org/?q=node/14. Accessed July 15, 2010.
³ Hematologica 2008; 93(s1): 47 Abstract 0118
⁴ Rosti G. et al. Excellent Outcomes at 3 Years with Nilotinib 800 Mg Daily In Early Chronic Phase, Ph+ Chronic Myeloid Leukemia (CML): Results of a Phase 2 GIMEMA CML WP Clinical Trial. 52nd Annual Meeting of the American Society of Hematology. Abstract No. 359. December 6, 2010.
National Cancer Institute. General Information About Chronic Myelogenous Leukemia (PDQ).
⁵ Tasigna* Product Monograph dated July 20, 2010
⁶ Gleevec* Product Monograph dated June 17, 2010

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