EAST HANOVER, N.J., June 4 /PRNewswire/ -- Novartis announced today the launch of a global program, 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 leukemia.
This program is available to eligible patients in all phases of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) who are either resistant to or intolerant of treatment with Gleevec(R) (imatinib mesylate)* tablets. 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 Gleevec, Novartis launched a wide-ranging access program that enabled more than 9,000 patients around the world to obtain Gleevec 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 Gleevec."
Information about ENACT can be found on the clinical trial website of the US National Institutes of Health, http://www.clinicaltrials.gov/. Information is also available by calling 1-800-340-6843 or by visiting http://www.novartisclinicaltrials.com/. Physicians can access information at http://www.amn107.com/.
About nilotinib
Nilotinib represents the next generation targeted, oral therapy specifically designed to be the most selective inhibitor of Bcr-Abl, the definitive cause of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (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 Hematology (ASH) showed complete hematologic responses in 92% of patients in chronic phase, as well as hematologic responses in 76% of patients in accelerated phase and in 42% of patients in myeloid blast crisis. Cytogenetic responses were also seen in 53% of patients in chronic phase, 55% in accelerated phase and 29% 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.
About Gleevec
Gleevec (imatinib mesylate) tablets are indicated for the treatment of newly diagnosed adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. Follow-up is limited. Gleevec tablets are also indicated for the treatment of patients with Ph+ CML in blast crisis, in accelerated phase, or in chronic phase after failure of interferon- alpha (IFN-a) therapy.
Important Safety Information(1)
Severe (NCI Grades 3/4) lab abnormalities-including neutropenia (3%-48%), anemia (<1%-42%), thrombocytopenia (<1%-33%), and hepatotoxicity (3%-6%)-and severe adverse experiences (NCI Grades 3/4), including severe fluid retention (eg, pleural effusion, pulmonary edema, and ascites) and superficial edema (1.8%-11%), hemorrhage (1%-19%) and musculoskeletal pain (2%-9%), were reported among Gleevec patients. Severe fluid retention appears to be dose related, was more common in the advanced phase studies (where the dosage was 600mg/day), and is more common in the elderly. Patients should be weighed and monitored regularly for signs and symptoms of edema, which can be serious or life-threatening. There have also been reports, including fatalities, of cardiac tamponade, cerebral edema, increased intracranial pressure, and papilledema and gastrointestinal perforation.
Bullous dermatologic reactions (eg, erythema multiforme and Stevens- Johnson syndrome) have also been reported. In some cases, the reaction recurred upon rechallenge. Several postmarketing cases note a resolution or improvement of bullous reaction following dose reduction with or without supportive care.
Dose adjustments may be necessary due to hepatotoxicity, other nonhematologic adverse events, or hematologic adverse events. Therapy with Gleevec was discontinued for adverse events in 3% to 5% of patients.
Patients with severe hepatic impairment should be treated at a starting dose of 300 mg/day and should be closely monitored.
Gleevec is metabolized by the CYP3A4 isoenzyme and is an inhibitor of CYP3A4, CYP2D6, and CYP2C9. Dosage of Gleevec tablets should increase by at least 50% and clinical response should be carefully monitored in patients receiving Gleevec tablets with a potent CYP3A4 inducer such as rifampin or phenytoin. Examples of commonly used drugs that may significantly interact with Gleevec include acetaminophen, warfarin, erythromycin, and phenytoin. (Please see full prescribing information for other potential drug interactions).
For daily dosing of 800mg and above, dosing should be accomplished using the 400mg tablets to reduce exposure to iron.
Use of Gleevec tablets is contraindicated in patients with hypersensitivity to imatinib or to any other component of Gleevec tablets.
Women of childbearing potential should be advised to avoid becoming pregnant while taking Gleevec tablets.
Because of the potential for serious adverse reactions in nursing infants, women should be advised to avoid breast-feeding while taking Gleevec tablets.
Common Side Effects(1)
The majority adult patients who received Gleevec in clinical studies experienced adverse events at some time. Most adverse events were mild to moderate in severity. The most frequently reported adverse events (all Grades) were superficial edema (58%-74%), nausea (47%-73%), muscle cramps (28%-62%), vomiting (21%-58%), diarrhea (39%-57%), musculoskeletal pain (38%-49%), and rash with related terms (26%-47%).**
Supportive care may help the management of most mild to moderate adverse events so that the prescribed dose can be maintained whenever possible.
Gleevec tablets should be taken with food and a large glass of water to minimize gastrointestinal (GI) irritation. Gleevec tablets should not be taken with grapefruit juice.
The foregoing release contains forward-looking statements that can be identified by terminology such as "planned," "planning," "will," or similar expressions, or by express or implied discussions regarding potential new indications for nilotinib or potential future sales of nilotinib, or regarding the long-term impact of a patient's use of nilotinib. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with nilotinib to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that nilotinib will be approved for any additional indications in any market. Nor can there be any guarantee regarding potential future sales of nilotinib. Neither can there be any guarantee regarding the long-term impact of a patient's use of nilotinib. In particular, management's expectations regarding commercialization of nilotinib could be affected by, among other things, additional analysis of nilotinib clinical data; new clinical data; unexpected clinical trial results; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry, and general public pricing pressures; and other risks and factors referred to in the Company's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
About Novartis
Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including central nervous system disorders, organ transplantation, cardiovascular diseases, dermatological diseases, respiratory disorders, cancer and arthritis. The company's mission is to improve people's lives by pioneering novel healthcare solutions.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG -- a world leader in pharmaceuticals and consumer health. In 2005, the Group's businesses achieved sales of USD 32.2 billion and pro forma net income of USD 6.1 billion. The Group invested approximately USD 4.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 91,000 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com/.
* Known as Glivec(R) (imatinib) outside the US
** Numbers indicate the range of percentages in 4 studies among adult
patients with Ph+ CML in blast crisis, accelerated phase, and chronic
phase.
1. Gleevec(R) (imatinib mesylate) tablets prescribing information. East
Hanover, NJ: Novartis Pharmaceuticals Corporation; 2005.
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