Clinical trial results demonstrate greater efficacy of nilotinib over imatinib for Ph+ CML

In a large clinical trial, nilotinib demonstrated greater efficacy over the current gold standard treatment, imatinib, in adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML) in the chronic phase.

In the first head-to-head study of these two oral treatments as initial therapy for this life-threatening leukaemia, nilotinib demonstrated statistically significant improvement over imatinib in key measures of effectiveness used in the trial. These new data were presented as a late breaker abstract at the 51st annual meeting of the American Society of Haematology (ASH), held 5-8 December 2009, in New Orleans, USA.

CML accounts for more than one in six leukaemias in adults, with around 600 new cases being registered in England and Wales each year. The estimated prevalence of CML in 2003 in England and Wales was 2,660 patients.

The trial showed that at 12 months, significantly fewer patients on nilotinib 300mg twice-daily progressed from the initial chronic phase of the disease to the later accelerated or blast crisis phases than those on imatinib 400mg once-daily. This demonstrates that nilotinib provided significantly better control of the disease compared to imatinib.

Nilotinib was generally well tolerated in the study. A small number of patients discontinued due to adverse events.

"The impressive rates of response observed in this study, combined with the very low rate of disease progression seen in nilotinib-treated patients are very encouraging," said Professor Richard Clark, Consultant Haematologist at Royal Liverpool University Hospital and a trialist involved in this study. "Continued improvement in the treatment of Ph+ CML is very important and these results indicate that nilotinib may provide long-term improvement in progression-free survival."

95% of patients with CML have an abnormality known as the Philadelphia chromosome. This chromosome produces a type of protein called Bcr-Abl, which is responsible for the overproduction of the cancerous white blood cells that are the main feature in Ph+ CML. Nilotinib is a potent and selective inhibitor of the Bcr-Abl protein, thereby inhibiting the production of these cancerous cells.

"Novartis has been at the forefront of research on the molecular origin of Ph+ CML and this has led to the development of treatments with unprecedented effectiveness and safety," said Panos Alexakos, Oncology Business Unit Head for Novartis UK. "These data are exciting and the deeper molecular response demonstrated provides hope for further improvement in outcomes for patients with Ph+ CML in the future."

Novartis plans to file worldwide applications for approval of nilotinib as a treatment for adult patients with newly diagnosed Ph+ CML. Nilotinib is currently approved in more than 80 countries including the European Union (EU), United States and other countries for the treatment of adult patients with Ph+ CML in chronic phase or accelerated phase who are resistant or intolerant to prior treatment including imatinib.