The US Food and Drug Administration (FDA) and Swissmedic have also approved Tasigna in this first-line indication. Regulatory submissions are under review in other countries worldwide.
“The approval of Tasigna for newly diagnosed Ph+ CML patients in chronic phase illustrates the Novartis commitment to continue challenging and advancing the science for treating cancer,” said Hervé Hoppenot, President, Novartis Oncology. “Tasigna was developed because we believed we could improve upon the standard of care to meet patients’ unmet needs, and as a result, patients now have a new and effective option for the treatment of CML.”
In laboratory studies, Tasigna has been shown to be a potent and selective inhibitor of the Bcr-Abl protein that causes production of cancer cells in Ph+ CML,. It is also active against a broad spectrum of Bcr-Abl mutations associated with resistance to Glivec.
In its pivotal head-to-head trial, Tasigna surpassed Glivec in key measures of treatment efficacy, as has been previously reported. Tasigna eliminated Bcr-Abl faster and more deeply than Glivec and resulted in lower rates of cancer progression after 12 months of therapyajor molecular response (MMR), a measure of deep reduction in Bcr-Abl, is considered to be a critical therapeutic milestone associated with good long-term outcomes for patients with Ph+ CML in chronic phase[6-8]. Treatment with Tasigna led to higher rates of both MMR and complete cytogenetic response (CCyR) (undectable Philadelphia chromosome that is the hallmark of this cancer) compared with Glivec.
After a median of 18 months of follow-up treatment, two patients on the Tasigna 300 mg twice daily arm progressed to either accelerated phase or blast crisis while 17 patients on the Glivec arm progressed to either accelerated phase or blast crisis. In the study, Tasigna and Glivec were well tolerated. Fewer patients discontinued due to adverse events from the Tasigna 300 mg twice daily arm of the study compared to the Glivec 400 mg once daily arm.
The randomized, open-label, multicenter trial called ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+ CML Patients), compared the efficacy and safety of Tasigna versus Glivec in adult patients with newly diagnosed Ph+ CML in chronic phase. It is the largest global randomized comparison of two oral therapies ever conducted in newly diagnosed Ph+ CML patients in chronic phase.
This year, Novartis also began a collaboration with molecular diagnostics company Cepheid to develop a new FDA cleared/approved Bcr-Abl test, which adheres to the International Scale. The goal of the collaboration is to help doctors more reliably monitor Ph+ CML patients. Cepheid and Novartis also will develop a next generation test, which is expected to enable even more sensitive testing, indicating the depth of a patient’s response to tyrosine kinase inhibitors, including Tasigna and Glivec. Currently, there are no FDA cleared/approved tests to monitor for Bcr-Abl.
Tasigna is indicated for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia (CML) in the chronic phase.
Tasigna has also been approved in over 90 countries for the treatment of chronic phase (CP) and accelerated phase Ph+ CML in adult patients resistant or intolerant to at least one prior therapy, including Glivec. The effectiveness of Tasigna for this indication is based on confirmed hematologic and unconfirmed cytogenetic response rates. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.
Tasigna is not approved in the EU for the treatment of newly diagnosed Ph+ CML-CP.
Tasigna important safety information
Tasigna should be taken twice daily at an interval of approximately 12 hours apart and must not be taken with food. No food should be consumed for two hours before the dose and for at least one hour after the dose. Avoid grapefruit juice and other foods that are known to inhibit CYP3A4.
Tasigna should not be used in patients who are hypersensitive to nilotinib or any of the excipients.
Treatment with Tasigna has been associated with hematological side effects such as thrombocytopenia, neutropenia and anemia, which was generally reversible and usually managed by withholding Tasigna temporarily or dose reduction. Complete blood counts should be performed every two weeks for the first two months and then monthly thereafter as clinically indicated.
Tasigna should be used with caution in patients with uncontrolled or significant cardiac disease (e.g., recent heart attack, congestive heart failure, unstable angina or clinically significant bradycardia), as well as in patients who have or may develop prolongation of QTc. These include patients with abnormally low potassium or magnesium levels, patients with congenital long QT syndrome, patients taking anti-arrhythmic medicines or other drugs that may lead to QT prolongation. Low levels of potassium or magnesium must be corrected prior to Tasigna administration. Close monitoring for an effect on the QTc interval is advisable and a baseline electrocardiography is recommended prior to initiating therapy with Tasigna and as clinically indicated. Uncommon cases (0.1 to 1%) of sudden death have been reported in clinical studies in patients with significant risk factors.
Tasigna should be used with caution in patients with liver impairment, in patients with a history of pancreatitis and in patients with total gastrectomy. Patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption should not use Tasigna. Tasigna should not be used during pregnancy unless clearly necessary and breast feeding is not recommended during treatment.
The most frequent Grade 3 or 4 adverse events for Tasigna were primarily hematological in nature and included neutropenia and thrombocytopenia. Elevations seen in bilirubin, liver function tests, lipase enzymes and blood sugar were mostly transient and resolved over time. These cases were easily managed and rarely led to discontinuation of treatment. Pancreatitis was reported in less than 1% of cases. The most frequent non-hematologic drug-related adverse events were rash, pruritus, nausea, fatigue, headache, alopecia, myalgia, constipation and diarrhea. Most of these adverse events were mild to moderate in severity.