Novartis announced that Tasigna (nilotinib) has been granted priority review by the US Food and Drug Administration (FDA) for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML) in chronic phase.

FDA priority review status is granted to therapies that offer major advances in treatment or provide a treatment where no adequate therapy exists. This status accelerates the standard review time from 10 to six months. Tasigna demonstrated that significantly fewer patients progressed to more advanced stages of the disease than the standard of care Glivec (imatinib) at 12 months. Tasigna also showed a statistically significant improvement over Glivec in every other measure of efficacy in the trial, including major molecular response (MMR) and complete cytogenetic response (CCyR) at 12 months.

In addition to the US, regulatory submissions have been filed in the EU and Japan. All filings are based on data showing superior efficacy for Tasigna in the first head-to-head comparison of the drug against the standard of care Glivec in newly diagnosed Ph+ CML patients. If approved for the first-line indication, Tasigna will be the first drug for newly diagnosed patients to become available since the approval of Glivec in 2002.

"Recently presented data showed that Tasigna surpassed Glivec in every measure of treatment efficacy designated in the study including prevention of disease progression at 12 months," said David Epstein, CEO of the Novartis Pharmaceuticals Division. "Now this priority review designation brings us one step closer to offering patients who are newly diagnosed with Ph+ CML in the chronic phase a promising new treatment option."

The regulatory submissions are based on data from the ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+ CML Patients) phase III clinical trial. This randomized, open-label, multicenter trial 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 the ENESTnd clinical trial, significantly fewer patients at 12 months progressed to accelerated or blastic phase on Tasigna 300 mg twice daily than on Glivec 400 mg once daily (2 patients vs. 11 patients), demonstrating a significant improvement in disease control. 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. No patients in the study had a prolongation of the QT interval >500 milliseconds. In addition, no sudden deaths occurred with either treatment.

Tasigna is a potent and selective inhibitor of the Bcr-Abl protein that causes production of cancer cells in Ph+ CML. The first clinical trials of Tasigna began 21 months after its discovery, with the drug receiving its first regulatory approval in the second-line indication in 2007.

CML is a disease in which the body produces cancerous white blood cells. Almost all patients with CML have an abnormality known as the Philadelphia chromosome, which produces a protein called Bcr-Abl. Bcr-Abl causes malignant white blood cells to proliferate. Worldwide, CML is responsible for approximately 10 to 15% of all adult cases of leukaemia, with an incidence of one to two cases per 100,000 people per year.

Tasigna has been approved in more than 80 countries for the treatment of chronic phase 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 haematologic and unconfirmed cytogenetic response rates. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.

Because taking Tasigna with food may increase the amount of drug in the blood, Tasigna should not be taken with food and patients should wait at least two hours after a meal before taking Tasigna. In addition, no food should be consumed for at least one hour after the dose is taken.

The most frequent Grade 3 or 4 adverse events for Tasigna were primarily haematological 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 rarely led to discontinuation of treatment. Pancreatitis was reported in less than 1% of cases. The most frequent non-haematologic drug-related adverse events were rash, pruritus, nausea, fatigue, headache, constipation and diarrhoea. Most of these adverse events were mild to moderate in severity.

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 echocardiogram is recommended prior to initiating therapy with Tasigna and as clinically indicated.

Glivec is approved in more than 90 countries, including the US, EU and Japan, for the treatment of all phases of Ph+ CML. Glivec is also approved in the US, EU and other countries for the treatment of patients with Kit (CD117)-positive gastrointestinal tumours (GIST), which cannot be surgically removed and/or have already spread to other parts of the body (metastasized). In the US and EU, Glivec is now approved for the post-surgery treatment of adult patients following complete surgical removal of Kit (CD117)-positive gastrointestinal stromal tumours. In the EU, Glivec is also approved for the treatment of adult patients with newly diagnosed Ph+ acute lymphoblastic leukaemia (Ph+ ALL) in combination with chemotherapy and as a single agent for patients with relapsed or refractory Ph+ ALL. Glivec is also approved for the treatment of adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP) who are not eligible for surgery. Glivec is also approved for the treatment of patients with myelodysplastic/myeloproliferative diseases (MDS/MPD). Glivec is also approved for hypereosinophilic syndrome and/or chronic eosinophilic leukaemia (HES/CEL).

The effectiveness of Glivec is based on overall hematological and cytogenetic response rates and progression-free survival in CML, on hematological and cytogenetic response rates in Ph+ ALL, MDS/MPD, on haematological response rates in systemic mastocytosis (SM), HES/CEL, on objective response rates and progression-free survival in unresectable and/or metastatic GIST, on recurrence free survival in adjuvant GIST and on objective response rates in DFSP. Increased survival in controlled trials has been demonstrated only in newly diagnosed chronic phase CML and GIST.