Novartis announced the launch of a global programme, ENACT (Expanding Nilotinib Access in Clinical Trials), to provide expanded access to nilotinib (AMN107), a compound currently in late-stage registration trials for treating certain forms of the life-threatening disease leukaemia.
This programme is available to eligible patients in all phases of Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML) who are either resistant to or intolerant of treatment with Glivec (imatinib). Novartis is now planning to submit nilotinib for US and EU regulatory approval in late 2006 compared to earlier estimates for submissions in 2007.
"ENACT is another example of our ongoing commitment to making innovative therapies available to patients who need new treatment options," said David Epstein, President of Novartis Oncology. "With Glivec, Novartis launched a wide-ranging access programme that enabled more than 9,000 patients around the world to obtain Glivec at no cost before it became commercially available. This program continues our dedication to patients by providing an option to those who are no longer responding to Glivec."
Information about ENACT can be found on the clinical trial website of the US National Institutes of Health, www.clinicaltrials.gov. Information is also available by contacting the Novartis local offices or local call centre, which will refer requests to the appropriate clinical team. Physicians can access information at www.amn107.com.
Nilotinib represents the next generation targeted, oral therapy specifically designed to be the most selective inhibitor of Bcr-Abl, the definite cause of Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML), and its mutations. Designed in the biomedical research facilities of Novartis, nilotinib is a tyrosine kinase inhibitor with high affinity and specificity to attach itself to Bcr-Abl, the definitive cause of Ph+ CML, and 32 of 33 mutant forms most commonly associated with the disease.
The US Food and Drug Administration (FDA) has granted both fast track designation and orphan drug status to nilotinib. Nilotinib also received orphan drug status from the European Medicines Evaluation Agency (EMEA).
As an investigational compound, the safety and efficacy profile of nilotinib has not yet been established. Data from a Phase I clinical trial presented at the 2005 Annual Meeting of the American Society of Haematology (ASH) showed complete haematologic responses in 92 per cent of patients in chronic phase, as well as haematologic responses in 76 per cent of patients in accelerated phase and in 42 per cent of patients in myeloid blast crisis. Cytogenetic responses were also seen in 53 per cent of patients in chronic phase, 55 per cent in accelerated phase and 29 per cent in myeloid blast crisis.
Access to nilotinib 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 FDA and the EMEA 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.
The majority of patients treated with Glivec experienced adverse events at some time. Most events were of mild to moderate grade and treatment was discontinued for adverse events only in 2 per cent of patients in chronic phase, 3 per cent in accelerated phase and 5 per cent in blast crisis. The most common side effects included nausea, superficial edema, muscle cramps, skin rash, vomiting, diarrhoea, haemorrhage, fatigue, headache, joint pain, cough, dizziness, dyspepsia and dyspnoea, as well as neutropenia and thrombocytopenia.
Glivec is contraindicated in patients with known hypersensitivity to imatinib or any of its excipients. Women of childbearing potential should be advised to avoid becoming pregnant while taking Glivec.