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About Tasigna®
Tasigna is a next-generation tyrosine kinase inhibitor, designed to meet the needs of Ph+ CML adult patients resistant to or intolerant to at least one prior therapy, including imatinib.
Clinical development of Glivec® (imatinib mesylate) has demonstrated that targeted inhibition of Bcr-Abl kinase activity has considerable clinical efficacy in patients with Ph+ CML.1 Indeed, 5-year follow-up of imatinib-treated patients in the original IRIS clinical trial shows a 95% overall survival rate.2 However, a small percentage of patients fail to achieve an adequate response to imatinib or lose their response over time.3 And while adverse events with imatinib are generally mild to moderate and can be managed, a small percentage of patients discontinue imatinib therapy due to severe side effects.4
Tasigna is a next-generation tyrosine kinase inhibitor that preferentially targets Bcr-Abl in vitro and has shown efficacy and safety in the treatment of Ph+ CML in adults resistant or intolerant to at least one prior therapy, including imatinib.5
Tasigna was designed to preferentially target Bcr-Abl — the key cause and driver of Ph+ CML.6
Tasigna
- Binds more effectively to Bcr-Abl in vitro than Glivec6, 7
- Achieves a higher intracellular concentration than Glivec6, 7
- Is active against 32 out of the 33 Bcr-Abl mutations most commonly associated with resistance to Glivec5, 6, 7
- Demonstrates minimal cross-intolerance with Glivec8
The chemical structure of Tasigna was based on imatinib with the intent of enhancing Bcr-Abl inhibition and specificity.7 Similarly to imatinib, the active ingredient in Tasigna, nilotinib, binds to the adenosine triphosphate binding site of Bcr-Abl and inhibits phosphotransferase activity of the Bcr-Abl tyrosine kinase.6, 9 Interruption of Bcr-Abl signaling cascades in leukemic cells with nilotinib ultimately leads to decreased cell proliferation and promotion of apoptosis.10
Tasigna produces rapid and durable response.11
- In clinical trials, the majority of patients (74%) in chronic phase who were resistant to or intolerant of Glivec achieved a complete hematologic response (CHR) with Tasigna.
- 52% of Ph+ CML patients in chronic phase achieved a major cytogenetic response (CyR) with Tasigna.
- Median time to major CyR in patients in the chronic phase was 2.8 months.
- The majority of patients experienced ongoing response during 10 months of follow-up (median duration not yet reached).
The tolerability of Tasigna can allow more patients to experience the benefits of continued Bcr-Abl inhibition.12
- In clinical trials, few patients intolerant to Glivec discontinued due to adverse events (AEs).
- High median dose intensity was achieved in clinical trials.
- Patients experienced limited hematologic and minimal nonhematologic AEs.
1. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344:1031-1037.
2. Druker BJ, Guilhot F, O'Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408-2417.
3. Shah, Neil. "Loss of Response to Imatinib: Mechanics and Management." Hematology (2005): 183-87.
4. Deininger MW, O’Brien SG, Ford JM, Druker BJ. Practical management of patients with chronic myeloid leukemia receiving imatinib. J Clin Oncol. 2003;21:1637-1647.
5. Kantarjian H, Wunderle L, Giles F, et al, "Nilotinib in Imatinib-Resistant CML and Philadelphia Chromosome–Positive ALL," N Engl J Med. 354, no. 24 (2006).
6. O’Hare T, Walters DK, Stoffregen EP, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 2005;65:4500-4505.
7.Weisberg E, Manley PW, Breitenstein W, et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell. 2005;7:129-141.
8. TASIGNA® (nilotinib) basic prescribing information. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2007.
9. Schindler T, Bornmann W, Pellicena P, Miller WT, Clarkson B, Kuriyan J. Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science. 2000;289:1938-1942.
10. Aichberger KJ, Mayerhofer M, Krauth MT, et al. Low-level expression of proapoptotic Bcl-2-interacting mediator in leukemic cells in patients with chronic myeloid leukemia:role of BCR/ABL, characterization of underlying signaling pathways, and reexpression by novel pharmacologic compounds. Cancer Res. 2005;65:9436-9444
11. Nilotinib Summary of Clinical Efficacy in CML-CP or CML-AP: 120-Day Update. Novartis Pharmaceuticals: East Hanover, NJ; 2007.
12. Nilotinib Summary of Clinical Safety: 120-Day Safety Update. Novartis Pharmaceuticals: East Hanover, NJ; 2007.
