New clinical data presented today demonstrated that Tasigna? (nilotinib) eliminated or significantly reduced the presence of blood cells containing a defective chromosome in approximately half of adult patients with a form of life-threatening leukemia who developed resistance or intolerance to treatment with Glivec? (imatinib).
The reductions achieved in these patients resistant to Glivec, one of the first oncology drugs developed based on an understanding of how some cancer cells work, may be the highest ever reported with a targeted therapy at a minimum of six months follow-up.
The Phase II data, which forms the basis for US and EU regulatory submissions completed earlier in 2006, showed that the use of Tasigna in patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) reduced or eliminated the presence of this defective chromosome in 51% of Glivec-resistant patients in chronic phase of this disease and led to normalized white blood cell counts in 74% of these patients.
The study also showed a similar magnitude of elimination or reduction of these defective cells in 55% of intolerant patients. Data from this trial were presented today at the American Society of Hematology annual meeting.
Novartis has filed applications with both the US Food and Drug Administration (FDA) and European Medicines Agency (EMEA) for Tasigna as a therapy for adult patients with chronic or accelerated phase Ph+ CML with intolerance and/or resistance to Glivec.
Tasigna was developed by Novartis as a next-generation targeted therapy based on the success of Glivec. Although data from the landmark IRIS trial – the largest-ever conducted in CML patients – demonstrated that nearly 90% of chronic-phase Ph+ CML patients taking Glivec were alive at five years, a small subset of patients develop resistance or cannot tolerate this therapy.
Both Tasigna and Glivec are designed to inhibit production of cells containing the Philadelphia chromosome by inhibiting the Bcr-Abl protein. Bcr-Abl is recognized as the key cause and driver of the proliferation of white blood cells that characterizes Ph+ CML.
While Tasigna and Glivec target the same pathways, the strategy behind the Tasigna research program was to design a preferentially Bcr-Abl targeted therapy that would be more potent against Glivec mutations but avoid the potential side effects of less targeted agents.