Mechanism of Action
TASIGNA (nilotinib) is a second-generation, selective TKI, approximately 30-fold more potent than imatinib
Because BCR-ABL is a key cause of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) and remains the driver of the disease throughout the chronic phase, BCR-ABL inhibition is the focus of CML treatment.1,2 Imatinib confirmed BCR-ABL as an effective target in Ph+ CML, but because some patients developed resistance or intolerance to imatinib, Novartis Oncology scientists continued the search for a Ph+ CML therapy that would more effectively target BCR-ABL.3 TASIGNA was designed to be a more potent and selective inhibitor of BCR-ABL in vitro than imatinib.3
TASIGNA is a better topological fit than imatinib for the kinase-binding domain3 with superior efficacy vs imatinib.4 The ENESTnd study showed that patients with newly diagnosed Ph+ CML taking TASIGNA achieve earlier and deeper reductions in BCR-ABL and have lower rates of progression than those taking imatinib.4 Study 2101 demonstrated second-line TASIGNA efficacy following imatinib.4
TASIGNA was designed to be a more potent and selective inhibitor of BCR-ABL in vitro than imatinib3
TASIGNA Therapeutic Indications4
TASIGNA is indicated for the treatment of adult patients with:
- Newly diagnosed Philadelphia chromosome positive chronic myelogenous leukemia (CML) in the chronic phase.
- Chronic phase and accelerated phase Philadelphia chromosome positive CML with resistance or intolerance to prior therapy including imatinib. Efficacy data in patients with CML in blast crisis are not available.
CP, chronic phase; MMR, major molecular response; MR4, molecular response 4 (4-log reductions); MR4.5, molecular response 4.5 (4.5-log reductions).
ENESTnd is a Phase III, randomized, open-label, multicenter study of 846 patients with newly diagnosed Ph+ CML in chronic phase who received TASIGNA 300 mg BID, TASIGNA 400 mg BID, or imatinib 400 mg QD. The primary endpoint was MMR at 12 months.
The 2101 study was a large, open-label, registration trial in imatinib-resistant or -intolerant patients with separate treatment arms for chronic phase (n=321) and accelerated phase (n=137) disease. Imatinib-intolerant patients had discontinued imatinib because of toxicity and were not in MCyR at the time of study entry. The primary endpoint in chronic phase patients was MCyR.
- Hochhaus A, et al. Leukemia. 2002;16(11):2190-2196.
- Shah NP, et al. Cancer Cell. 2002;2(2):117-125.
- Weisberg E, et al. Nat Rev Cancer. 2007;7(5):345-356.
- TASIGNA® (nilotinib) Summary of Product Characteristics. Basel, Switzerland: Novartis Pharma AG; May 2017.