The first-ever published clinical trial data about the investigational drug Tasigna (nilotinib) showed the compound helped more than 90 per cent of patients diagnosed with an unresponsive form of leukaemia, a life-threatening disease.
The data were published in the New England Journal of Medicine.
In less than five months of treatment, 92 per cent of patients with chronic phase Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML) achieved a complete haematologic response with normal white blood cell counts after having shown resistance or intolerance to optimized Glivec (imatinib) therapy.
In more than a third of these patients, the Ph chromosome, the genetic abnormality that characterizes most cases of CML, was undetectable after treatment with Tasigna, as measured by standard laboratory methods. A total of 106 patients with Ph+ CML participated in this study: 33 patients in blast crisis, 56 patients in accelerated phase, and 17 patients in chronic phase. In addition, 13 patients with Ph+ acute lymphoblastic leukemia were included in the study.
Both Tasigna and Glivec inhibit Bcr-Abl, the definitive cause of Ph+ CML - in effect, shutting down production of the Ph chromosome. Tasigna was specifically designed to be a more selective inhibitor of Bcr-Abl and its mutations, which can cause resistance to treatment.
"By selectively inhibiting Bcr-Abl and its common mutations, Tasigna produced dramatic positive responses in patients who had limited treatment options," said Hagop Kantarjian, MD, Professor of Medicine and Internist, Chair, Department of Leukaemia, M.D. Anderson Cancer Center. "These extremely encouraging results reinforce the validity of treating this cancer by specifically targeting the one protein known to cause the disease."
Patients in the most advanced phases of CML responded to Tasigna therapy. The overall rate of haematologic response (normalization of white blood cell counts) for patients in accelerated phase was 72 per cent and the rate of cytogenetic response (reduction or elimination of the Ph+ chromosome) was 48 per cent. Among patients in blast crisis, the response rates were 39 per cent and 27 per cent, respectively.
The study investigators concluded that Tasigna was generally well tolerated. Common adverse events included myelosuppression, transient indirect hyperbilirubinemia and skin rashes. Additionally, the investigators noted that Tasigna was usually not associated with common toxicities seen with Glivec (e.g. fluid retention, superficial edema, weight gain), or rare cases of pleural and pericardial effusions.
Discovered in the biomedical research facilities of Novartis, Tasigna (investigational name AMN107) entered Phase I clinical studies just 21 months after it was first synthesized. It is a next generation tyrosine kinase inhibitor in Ph+ CML with a high affinity and specificity to attach itself to Bcr-Abl and to 32 of 33 mutant forms commonly associated with Ph+ CML. The US Food and Drug Administration (FDA) has granted both fast track designation and orphan drug status to Tasigna. Tasigna also received orphan drug status from the European Medicines Agency (EMEA). Novartis is now planning to submit Tasigna for US and EU regulatory approval in late 2006 compared to earlier estimates for submissions in 2007.
As an investigational compound, the safety and efficacy profile of Tasigna has not yet been established. Access to Tasigna is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the compound's potential benefits and risks and data will be filed with regulatory authorities such as the U.S. FDA and the European Medicines Agency for regulatory approval.
Glivec is approved in more than 90 countries including the US, EU and Japan for the treatment of all phases of Ph+ CML.
The effectiveness of Glivec is based on overall haematologic and cytogenetic response rates and progression-free survival in CML. There are no controlled trials demonstrating increased survival.