Following a priority review, the US Food and Drug Administration (FDA) has approved Tasigna (nilotinib) for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML) in chronic phase. With this approval, Tasigna becomes the first new therapeutic option for newly diagnosed patients since the introduction of Glivec (imatinib), providing a major advance for patients with this blood cancer.

The US approval was based on results of the ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+ CML Patients) phase III clinical trial, which were published in The New England Journal of Medicine (NEJM).

"With the faster and deeper responses we are seeing with Tasigna, newly diagnosed CML patients will have a new and more effective treatment option," said Hervé Hoppenot, president, Novartis Oncology.

Tasigna is 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. The first clinical trials of Tasigna began only 21 months after its discovery, with the drug receiving its first regulatory approval as a second-line treatment in 2007.

In its pivotal head-to-head trial against Glivec, Tasigna surpassed Glivec in key measures of treatment efficacy, as has been previously reported. Tasigna eliminated Bcr-Abl faster than Glivec, resulting in lower rates of cancer progression even as early as 12 months. Deep reduction of Bcr-Abl, known as a major molecular response, is considered to be a critical therapeutic milestone associated with good long-term outcomes for patients with Ph+ CML. Treatment with Tasigna led to higher rates of both major molecular response and complete cytogenetic response (elimination of the Philadelphia chromosome that is the hallmark of the cancer) compared with Glivec.

The randomized, open-label, multi-centre ENESTnd 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 chronic phase.

Two patients on the nilotinib arm progressed to either accelerated phase or blast crisis while 17 patients on the imatinib arm progressed to either accelerated phase or blast crisis. In the study, Tasigna was 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. No patients in the study had a prolongation of the QT interval >500 milliseconds. In addition, no sudden deaths occurred with either treatment.

Regulatory submissions for Tasigna in the first-line indication are under way worldwide, with applications currently filed in the EU, Switzerland and Japan.

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 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.

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 tumors (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 haematological 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.