Tasigna (nilotinib) has been approved in the US as a new anti-cancer therapy for certain patients with a life-threatening form of leukaemia who are resistant or intolerant to prior treatment including Glivec (imatinib), an established treatment standard and a leading Novartis medicine.

Novartis will make Tasigna available throughout the US within days following this approval by the Food and Drug Administration (FDA) to meet the treatment needs of these patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML), a Novartis press release stated.

CML is one of the four most common types of leukaemia, a form of blood cancer, and affects around 4,500 people in the US each year.

"Tasigna represents an important advance for the small number of patients who are resistant or intolerant to prior therapy. This approval means we can offer physicians a comprehensive treatment approach with effective medicines to treat their Ph+ CML patients," said David Epstein, President and CEO, Novartis Oncology.

Taken twice daily, Tasigna works by inhibiting the proliferation of cells containing an abnormal chromosome. It does this by targeting the production of the Bcr-Abl protein, which is produced only by cells containing the abnormal Philadelphia chromosome. This protein is recognized as the key cause and driver of the overproduction of cancer-causing white blood cells in patients with Ph+ CML. Tasigna was specifically designed to target the Bcr-Abl protein more preferentially than Glivec without adding new mechanisms of action. At six months follow-up, Tasigna reduced or eliminated cells carrying the abnormal Philadelphia chromosome in 40 per cent of patients in chronic phase of the disease.

Applying experience gained from the development of Glivec, which remains the most frequently prescribed treatment for patients with CML, a team of Novartis scientists created Tasigna in August 2002, just a year after the launch of Glivec. In preclinical studies, the medicine was able to overcome resistance resulting from Bcr-Abl kinase mutations in 32 of 33 cell lines commonly associated with Ph+ CML. Patients with a variety of these mutations also responded to treatment with Tasigna.

The first worldwide approval for Tasigna came in Switzerland in July 2007. European Union approval is expected by the end of this year after the Committee for Medicinal Products for Human Use (CHMP), which reviews medicines in Europe, issued a positive opinion in September. Tasigna was also submitted for approval in Japan in June.

In clinical trials, the primary endpoint for patients in chronic phase was unconfirmed major cytogenetic response (MCyR). After a minimum follow-up of six months (median treatment duration 8.7 months), Tasigna produced MCyR in 40 per cent of 232 chronic phase patients evaluated for efficacy. The complete cytogenetic response in these patients was 28 per cent.

The highest prior Glivec dose was at least 600 mg/day in 77 per cent of patients, with 44 per cent of patients receiving doses of 800 mg/day or higher. In addition, 24 different mutations in Bcr-Abl were noted in 19 per cent of chronic phase and 25 per cent of accelerated phase CML patients who were evaluated for mutations.

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.

In countries where it is approved, Tasigna is indicated for the treatment of chronic phase and accelerated phase Philadelphia chromosome-positive chronic myelogenous leukaemia in adult patients resistant or intolerant to at least one prior therapy including Glivec. The effectiveness of Tasigna is based on hematologic and cytogenetic response rates. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.

The most frequent Grade 3 or 4 adverse events for Tasigna were primarily haematological in nature and included neutropenia and thrombocytopenia.

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 EU, US 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 (metastasised).

In Japan, Glivec is approved for the treatment of patients with Kit (CD117)-positive GIST. 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.

The majority of patients treated with Glivec in clinical trials experienced adverse events at some time. Most events were of mild to moderate grade and treatment discontinuation was not necessary in the majority of cases.