Tasigna demonstrates greater efficacy over Gleevec in chronic Ph+ CML patients

NOVARTIS CANADADec 11 2009

(Pr)Tasigna surpassed gold standard in all designated measures of efficacy, including prevention of disease progression at 12 months

In a large Phase III clinical trial, Tasigna (nilotinib capsules) demonstrated greater efficacy over Gleevec (imatinib) in the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase. The new clinical data were just presented as a late breaking abstract at the 51st annual meeting of the American Society of Hematology (ASH), in New Orleans, Louisiana.

CML is one of the four most common types of leukemia. 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. A form of blood cancer, CML is estimated to affect approximately 3,000 Canadians.

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).

At 12 months, the randomized, open-label, clinical trial (which included Canadian sites) named Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+ CML Patients (ENESTnd), found that significantly fewer patients progressed to the accelerated or blastic phases on Tasigna 300 mg twice daily than on Gleevec 400 mg once daily (2 patients vs. 11 patients), demonstrating a statistically significant improvement in disease control. Gleevec tablets are the established treatment standard.

In the first head-to-head comparison of two oral therapies as initial treatment for this blood cancer, Tasigna results showed statistically significant improvement over Gleevec in every measure of efficacy, including major molecular response (MMR) (reduction in the level of the abnormal Bcr-Abl protein, to less than or equal to 0.1% of the pre-treatment level based on an internationally agreed standard), complete cytogenetic response (CCyR - where no CML cells containing the Ph chromosome can be seen in a sample of bone marrow), and prevention of progression to the accelerated or blast crisis phases.

With Tasigna 300 mg twice daily, the rate of MMR at 12 months was twice that of patients receiving Gleevec 400 mg once daily (44% vs. 22%, p (less than) 0.0001). In addition, 80% of patients achieved CCyR with Tasigna vs. 65% with Gleevec 400 mg once daily (p (less than) 0.0001). All types of responses were achieved faster in the Tasigna group than in the Gleevec group.

"The strong response rates observed with Tasigna, combined with the very low rate of disease progression, indicate that patients who begin their treatment with Tasigna may have long-term improvement of progression-free survival," said Dr. Jeffrey Lipton, a haematological oncologist with Princess Margaret Hospital in Toronto, Ontario. "With Gleevec, the majority of chronic phase patients run into problems with disease progression early and the tolerability of Tasigna should support its use in newly diagnosed Ph+ CML patients," said Dr. Lipton.