Switzerland has granted the first worldwide approval for Tasigna (nilotinib), a potent and novel targeted cancer therapy for patients with a form of the life-threatening blood cancer chronic myeloid leukaemia (CML) who are resistant or intolerant to treatment with Glivecâ (imatinib). The leading therapy for CML patients also developed by Novartis.
The approval of Tasigna came after an accelerated review by the Swiss health authority Swissmedic based on positive findings from a pivotal phase II trial, Trial results showed high response rates in these patients with a generally well-tolerated, manageable safety profile.
Taken twice-daily, Tasigna inhibits production of cancer cells containing an abnormal chromosome by targeting the Bcr-Abl protein. This protein, which is produced by cells containing the abnormal Philadelphia chromosome, is recognized as the key driver of the overproduction of cancer-causing white blood cells in patients with CML.
In clinical trials, Tasigna reduced or eliminated this abnormal chromosome in 42 per cent of Glivec-resistant patients with Philadelphia chromosome-positive (Ph+) CML in the chronic phase of the disease, as well as in 31 per cent of patients in the accelerated phase of the disease.
"While over 90 per cent of patients on Glivec survive after five years, we focused on helping the small percentage of patients who developed resistance or intolerance to Glivec, which led to the discovery of Tasigna," said Dr Daniel Vasella, chairman and CEO of Novartis. "I am pleased that we set a record of less than five years from synthesis to market, rapidly bringing Tasigna - our second-generation, more selective and more potent Bcr-Abl tyrosine kinase inhibitor - to those patients who need it."
Additional regulatory decisions on Tasigna are expected in the US and Europe later this year, while a regulatory submission was completed in Japan during the second quarter of 2007. In the US, the Food and Drug Administration requested on July 16 a three-month extension in the regulatory review period.
Also planned for 2007 are phase III studies involving Tasigna in CML patients responding sub-optimally to other therapies as well as newly-diagnosed CML patients. A registration study is already underway in patients with gastrointestinal stromal tumours (GIST), which can also be treated with Glivec in certain countries.
Recent landmark clinical trial results for Glivec showed that nearly 90 per cent of newly-diagnosed chronic phase Ph+ CML adults patients treated with Glivec were alive after five years, but some develop resistance or cannot tolerate this therapy.
Applying key learning's from Glivec, a team of Novartis scientists created Tasigna in August 2002, just a year after the launch of Glivec. Tasigna was specifically designed to target Bcr-Abl more potently and preferentially without adding new mechanisms of action that might cause additional side effects. Tasigna moved from synthesis to its first regulatory approval in less than five years.
"The speed of developing Tasigna reflects our passion to help cancer patients," said David Epstein, President and CEO of Novartis Oncology. "A designer cancer treatment, Tasigna also highlights our leadership in targeted therapies."
Chronic myeloid leukaemia is one of the four most common types of leukaemia, responsible for about 15 per cent of all leukaemia cases worldwide, and caused by an overproduction of immature white blood cells. Approximately 95 per cent of CML patients have the Philadelphia chromosome.
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 (metastasized). Glivec has also been approved in various countries for use in treating patients with certain rare types of cancer.
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.