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Title: Tasigna® (Nilotinib) Receives U.S. Approval for Chronic Myeloid Leukemia in Patients With Resistance or Intolerance to Existing Therapies

"Tasigna® (Nilotinib) Receives U.S. Approval for Chronic Myeloid Leukemia in Patients With Resistance or Intolerance to Existing Therapies"

EAST HANOVER, CT -- October 30, 2007 -- Tasigna® (nilotinib) capsules have been approved in the US as a new therapy for certain patients with a life-threatening form of leukemia who are resistant or intolerant to prior treatment including Gleevec® (imatinib mesylate) tablets, an established treatment standard and a leading Novartis medicine. Novartis will make Tasigna available throughout the US within days following this approval by the Food and Drug Administration (FDA) to meet the treatment needs of these patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML). CML is one of the four most common types of leukemia, a form of blood cancer, and affects around 4,500 people in the US each year.1 "Tasigna represents an important advance for the small number of patients who are resistant or intolerant to prior therapy," said David Epstein, President and CEO of Novartis Oncology. "This approval means we can offer physicians a comprehensive treatment approach with effective medicines to treat their Ph+ CML patients." Taken twice daily, Tasigna works by inhibiting the proliferation of cells containing an abnormal chromosome. It does this by targeting the production of the Bcr-Abl protein, which is produced only by cells containing the abnormal Philadelphia chromosome. This protein is recognized as the key cause and driver of the overproduction of cancer-causing white blood cells in patients with Ph+ CML. Tasigna was specifically designed to target the Bcr-Abl protein more preferentially than Gleevec without adding new targets. At 6 months follow-up, Tasigna reduced or eliminated cells carrying the abnormal Philadelphia chromosome in 40% of patients in chronic phase of the disease. Applying experience gained from the development of Gleevec, which remains the most frequently prescribed treatment for patients with Ph+ CML, a team of Novartis scientists created Tasigna in August 2002, just a year after the launch of Gleevec. In preclinical studies, the medicine was able to overcome resistance resulting from Bcr-Abl kinase mutations in 32 of 33 cell lines commonly associated with Ph+ CML. Patients with a variety of these mutations also responded to treatment with Tasigna. The first worldwide approval for Tasigna came in Switzerland in July 2007. European Union approval is expected by the end of this year after the Committee for Medicinal Products for Human Use (CHMP), which reviews medicines in Europe, issued a positive opinion in September. Tasigna was also submitted for approval in Japan in June. 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).2 Recent landmark clinical trial results for Gleevec show that nearly 90% of newly diagnosed chronic-phase Ph+ CML adult patients treated with Gleevec were alive after five years,3 but some develop resistance or cannot tolerate this therapy. The FDA approved Tasigna for treatment of chronic-phase and accelerated-phase Ph+ CML in adult patients resistant or intolerant to prior treatment that included Gleevec. This approval is based on an open-label multicenter clinical trial evaluating the drug's safety and rates of cytogenetic response (i.e. reduction or elimination of the Philadelphia chromosome) and hematologic response (i.e. normalization of white blood cell counts) in Gleevec-resistant or -intolerant patients with Ph+ CML in chronic phase (n=280) and accelerated phase (n=105). In clinical trials, the primary endpoint for patients in chronic phase was unconfirmed major cytogenetic response (MCyR). After a minimum follow-up of 6 months (median treatment duration 8.7 months), Tasigna produced MCyR in 40% of 232 chronic-phase patients evaluated for efficacy. The complete cytogenetic response in these patients was 28%. For patients in accelerated phase, the primary endpoint was confirmed hematological response (HR). Complete HR was reported in 18% of patients in accelerated phase. (Accelerated-phase patients had a minimum follow-up of 4 months and a median treatment duration of 5.6 months). The highest prior Gleevec dose was greater than or equal to 600 mg/day in 77% of patients with 44% of patients receiving doses of 800 mg/day or higher. In addition, 24 different mutations in Bcr-Abl were noted in 19% of chronic-phase and 25% of accelerated-phase CML patients who were evaluated for mutations. Because taking Tasigna with food may increase the amount of drug in the blood, Tasigna should not be taken with food and patients should wait at least two hours after a meal before taking Tasigna. In addition, no food should be consumed for at least one hour after the dose is taken. About Tasigna Tasigna® (nilotinib) capsules are indicated for the treatment of chronic-phase and accelerated-phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) in adult patients resistant to or intolerant to prior therapy that included Gleevec® (imatinib mesylate) tablets. The effectiveness of Tasigna is based on hematologic and cytogenetic response rates. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival. About Gleevec Gleevec® (imatinib mesylate) tablets are indicated for the treatment of newly diagnosed adult patients with Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) in the chronic phase. Follow-up is limited to 5 years. Gleevec is also indicated for the treatment of patients with Ph+ CML in blast crisis (BC), accelerated phase (AP), or in the chronic phase (CP) after failure of interferon-alpha therapy. REFERENCES: 1. American Cancer Society. Overview: Leukemia – Chronic Myeloid (CML). http://www.cancer.org/docroot/CRI/content/CRI_2_2_1x_How_Many_People_Get_Chronic_Myeloid_Leukemia.asp?rnav=cri Last accessed October, 2007. 2. Faderl S; Talpaz M; Estrov Z; O'Brien S; Kurzrock R; Kantarjian HM. The biology of chronic myeloid leukemia. [N Engl J Med. 341:164-72, 1999.

3. Druker, B. et al. Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia. N Engl J Med 2006;355:2408-17.

* Known as Glivec® (imatinib) outside the US, Canada and Israel.

SOURCE: Novartis Pharmaceuticals Corporation

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