The Swiss health authority Swissmedic has granted approval for Tasigna (nilotinib) 300 mg twice daily for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML) in chronic phase. Tasigna is 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 approval of Tasigna came after being designated for a fast track review by Swissmedic based on positive findings at 12 months from a pivotal phase III trial, ENESTnd, demonstrating superiority to the standard of care Glivec in achieving molecular and cytogenetic response and delaying cancer progression. In June of this year, these findings were published in The New England Journal of Medicine and 18-month median data were presented at the 2010 annual meeting of the American Society of Clinical Oncology.

The US Food and Drug Administration approved Tasigna in the first-line indication in June. Other regulatory submissions are under review worldwide.

"Switzerland was the first country to approve Tasigna in 2007 for its original indication as a second-line treatment after Glivec. Now, with this approval of Tasigna as a first-line treatment, we are pleased to offer newly diagnosed CML patients a new and even more effective option for delaying disease progression," 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.

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 than Glivec, resulting in lower rates of cancer progression even after only 12 months of therapy. Deep reduction of Bcr-Abl, known as a major molecular response, is considered to be an important 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 at 12 months.

The randomized, open-label, multicenter ENESTnd trial (also known as 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.

At 12 months, two patients on the nilotinib arm progressed to either accelerated phase or blast crisis while 11 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. The ENESTnd trial is ongoing.

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 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 leukemia (HES/CEL).

The effectiveness of Glivec is based on overall haematological 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.