The pipeline of the affiliates of Novartis AG holds a broad stream of promising future products. Additional indications for marketed products are also being pursued.
The affiliates of Novartis AG's pioneering work in the field of targeted therapies continues with the development of the next generation of signal transduction inhibitors, including TASIGNA®, which was specifically designed to selectively inhibit Bcr-Abl.1
Discovered in the biomedical research facilities of Novartis, TASIGNA® (formerly AMN107) entered Phase I clinical studies in 2004, just 21 months after it was first synthesized in August 2002. Preclinical studies showed that TASIGNA® was active against wild-type, or nonmutant, BCR-ABL, as well as 32 of 33 Bcr-Abl mutants most frequently associated varying degrees of resistance to GLIVEC®.1
In the recently completed ENESTnd trial,* nilotinib demonstrated superior efficacy and favorable tolerability in newly diagnosed patients with Ph+ CML compared with imatinib.2
At 12 months2
- Major molecular response (MMR) for nilotinib (44% for the 300-mg dose and 43% for the 400-mg dose) was twice that for imatinib (22%) (P<0.001 for both comparisons)
- Of the 11 imatinib patients who progressed to AP or BC at 12 months, 3 had achieved complete cytogenetic response (CCyR)
- CCyR was significantly higher for nilotinib (80% for the 300-mg dose and 78% for the 400-mg dose) than for imatinib (65%) (P<0.001 for both comparisons)
- Nilotinib had a distinct adverse event profile vs imatinib, including low rates of myelosuppression, less peripheral edema, and fewer GI side effects
*ENESTnd study design: A randomized, controlled, multicenter Phase III trial of 846 patients with newly diagnosed Ph+ CML. Patients were randomized to receive either TASIGNA® 400 mg bid (n=281), TASIGNA® 300 mg bid (n=282), or imatinib 400 mg qd (n=283). The daily dose of imatinib could be dose escalated to 800 mg (400 mg bid), but no dose escalation was permitted with TASIGNA®. A centralized laboratory was used for quantitative reverse transcriptase polymerase chain reaction (RQ-PCR) testing.
In a separate 24-month follow up of a Phase II study,TASIGNA achieved impressive responses in adult patients with Ph+ CML who developed resistance or intolerance to treatment with GLIVEC.3
The estimated overall survival rate at 24 months with TASIGNAwas 88%. An MCyR was achieved in 59% of patients, a CCyR was achieved by 44% of patients, and in patients with a baseline CHR, 73% achieved MCyR. These cytogenetic responses were durable, as 78% and 83% of patients maintained MCyR and CCyR, respectively, at 24 months. 25% of patients also achieved major molecular response at 24 months.
TASIGNA has received regulatory approval in the United States, Europe, and over 50 other countries across the globe.
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Note: Before prescribing, please read full European Summary of Product Characteristics.
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References
- TASIGNA® (nilotinib) Summary of Product Characteristics. Basel, Switzerland: Novartis Pharma AG; 2010.
- Saglio G, Kim D-W, Issaragrisil S, et al; for ENESTnd investigators. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362(24):2251-2259.
- Kantarjian H, Giles FG, Bhalla KN, et al. Nilotinib in chronic myeloid leukemia patients in chronic phase (CML-CP) with imatinib resistance or intolerance: 24-month follow-up results of a phase 2 study. Haematologica. 2009;94(suppl 2):254-255. Abstract 0627.
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