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Lower Dose Sprycel™ Approved for Patients With Chronic Phase CML

Categories: Chronic myeloid leukemia (CML) | Sprycel

New once daily dose retains efficacy and improves tolerability

MONTREAL, CANADA – (December 15, 2008) – Health Canada has granted a conditional approval for a new lower recommended starting dose for SPRYCEL™ (dasatinib) of 100 mg once daily for adult Canadians living with chronic phase (CP) chronic myeloid leukemia (CML) who fail or are intolerant to currently approved therapies. Previously these patients began SPRYCEL therapy with a dose of 70 mg taken twice daily. The once a day dosing simplifies treatment for patients and the lower dose offers less side effects while preserving efficacy of the higher twice daily dose.

“This is good news for CML patients and doctors. Side effects are an important issue that can significantly impact patient quality of life and can result in missed doses, dose adjustments or treatment discontinuation. The lower starting dose for SPRYCEL, combined with the convenience of once daily dosing makes it easier for patients to comply with the prescribed regimen,” explains Dr. Jeff Lipton, medical oncologist and Associate Professor of Medicine at the University of Toronto. “This is good news from a clinician perspective, because what it provides us with is a lower dose of the drug with less side effects without compromising efficacy.”

The conditional approval of the new lower starting dose was based on data from a phase 3 dose-optimization study in chronic phase CML patients whose disease was resistant or intolerant to imatinib mesylate (marketed as Gleevec®). The lower SPRYCEL 100 mg once daily retained the efficacy of conventional 70 mg twice daily and was associated with consistently lower frequency of adverse events including a marked reduction of the incidence of pleural effusions and haematologic complications. The occurrence of side effects that affect day-to-day well-being including drug-related nausea and vomiting were also less frequently reported in the 100 mg daily treatment arm. Additionally, there were significantly fewer dose interruptions and discontinuations at 100 mg once daily.

However, by five years, about one-third of patients will fail to achieve a response, will lose the response, will progress to accelerated or blast phase or will develop intolerance to imatinib. The results of the dose-optimization study including the favourable overall risk-benefit profile of SPRYCEL 100 mg once daily confirm its importance in the treatment of these patients.

Patient response to SPRYCEL 100 mg daily

In the open-label phase 3 trial, 670 patients with imatinib-resistant or -intolerant chronic phase (CP) chronic myeloid leukemia (CML) were randomly assigned 1:1:1:1 between four SPRYCEL treatment groups: 100 mg once daily, 50 mg twice daily, 140 mg once daily, or 70 mg twice daily. The minimum follow-up time was 6 months (median treatment duration, 8 months; range, 1 to 15 months).

SPRYCEL was associated with marked and consistent hematologic and cytogenetic response rates at a median follow-up of only eight months (CHR, 86% to 92%; MCyR, 54% to 59%; CCyR, 41% to 45%), irrespective of schedule (once daily or twice daily) or total daily dose (100 mg or 140 mg).

Time to and duration of cytogenetic response were similar in all treatment groups, as was progression-free survival (8% to 11% of patients experienced disease progression or died).

Compared with the 70-mg twice daily regimen, SPRYCEL 100 mg once daily resulted in significantly lower rates of pleural effusion (all grades, 7% v 16%; P = .024) and grade 3 to 4 thrombocytopenia (22% v 37%; P = .004), and fewer patients required dose interruption (51% v 68%), reduction (30% v 55%), or discontinuation (16% v 23%). In general, pleural effusions resolved with temporary dose interruption, diuretics, and/or pulse corticosteroids. Drug-related nausea (15% v 25%) and vomiting (5% v 10%) of any grade occurred in fewer patients receiving 100 mg once daily than 70 mg twice daily.I

About CML

Chronic myeloid leukemia (CML), one of four known types of leukemia, is a slowly progressing cancer of the blood and bone marrow characterized by an overproduction of white blood cells. When the white blood cells produce uncontrollably, they do not mature to carry out their intended function and ultimately crowd out the healthy cells.II

CML is distinguished from the other types of leukemia by a genetic abnormality in the white blood cells called the Philadelphia chromosome which promotes the growth of leukemia cells and seems to be present in nearly 90 per cent of CML cases.III The Philadelphia chromosome is thought to be acquired after birth and is formed when two chromosomes (9 and 22) switch some of their gene material, forming a new chromosome.IV

In Canada, there are approximately 460 new cases of CML each year, which represents 1 case for every 100,000 people. It is estimated that approximately 3,000 Canadians are currently living with this very rare form of leukemia, which usually occurs during or after middle age.II

About SPRYCEL

SPRYCEL (dasatinib) is indicated for the treatment of adults with chronic, accelerated, or blast phase chronic myeloid leukemia (CML) with resistance or intolerance to prior therapy including imatinib mesylate. Conditional approval in CML of SPRYCEL is based on the rates of hematologic and cytogenetic responses. Duration of follow-up is limited. There are no controlled trials demonstrating a clinical benefit, such improvement in disease-related symptoms or increased survival. SPRYCEL is also indicated for the treatment of adults with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) with resistance or intolerance to prior therapy. Non-conditional approval in Ph+ ALL is based on the rates of hematologic and cytogenetic responses. Duration of follow-up is limited. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.V

SPRYCEL is an oral therapy. The recommended starting daily dose is 100 mg for chronic phase CML, administered once a day in the morning or in the evening. The medication can be taken with or without food.

SPRYCEL 20 mg, 50 mg and 70 mg tablets in CML are approved under Health Canada's Notice of Compliance with Conditions (NOC/c) policy. This approval was granted based on the promising nature of the clinical efficacy and safety data for SPRYCEL in patients with this serious disease. This policy is reserved for treatments that address a serious unmet medical need in Canada or have demonstrated a significant improvement in the benefit/risk profile over existing therapies. The NOC/c was granted on the basis that BMS will conduct additional studies to further evaluate the clinical benefits of the treatment.

SPRYCEL is available in more than 25 countries including the United States, Austria, Germany, France, Sweden and the United Kingdom.

About Bristol-Myers Squibb Canada

Bristol-Myers Squibb Canada is an indirect wholly-owned subsidiary of Bristol-Myers Squibb Company, a global pharmaceutical and related health care products company whose mission is to extend and enhance human life. Bristol-Myers Squibb Canada is a leading provider of medicines to fight cancer, cardiovascular and metabolic disorders, infectious diseases (including HIV/AIDS), nervous system diseases and serious mental illness. Bristol-Myers Squibb Company is listed on the New York Stock Exchange under the BMY symbol (NYSE:BMY). Bristol-Myers Squibb Canada's operations are headquartered in Montréal, Québec.

For further information, please contact:

Sabrina Tremblay
Senior Manager of Public Affairs
Bristol-Myers Squibb Canada
Tel.: 514-333-2463
[email protected]

Muriel Haraoui
HKDP Communications and public affairs
Tel.: 514-395-0375, extension 235
[email protected]

SPRYCELTM is a trademark of Bristol-Myers Squibb Company used under license by Bristol-Myers Squibb Canada ®Gleevec is a registered trademark of its respective owner and not of Bristol-Myers Squibb Company

I Shah NP, et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol. 2008 Jul 1;26(19):3204-12
II CML Society of Canada Understanding CML. Available at: http://www.cmlsociety.org/?q=node/14. Last viewed on December 12, 2008
III Faderl S, Talpaz M, Estrov Z, et al. The Biology of Chronic Myeloid Leukemia. N Engl J Med 1999;341(3):164-172
IV Medicinenet.com Definition of Philadelphia Chromosome (Ph) Available at: http://www.medterms.com/script/main/art.asp?articlekey=4870. Last viewed on December 12, 2008
V Bristol-Myers Squibb Canada SPRYCEL Product Monograph Revised October 14, 2008

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