Healthcare Industry News: Ph+ CML
News Release - May 10, 2006
Five years after approval, Gleevec underscores the promise of targeted therapy to provide sustained disease controlUnprecedented outcomes in Ph+ chronic myeloid leukemia (CML) patients validate the targeting of a specific cancer cause to create effective and well-tolerated therapies
First to show reduced annual progression rate with long-term use in newly diagnosed CML patients less than 1% progress to more advanced stages of disease in fourth treatment year
New data from the largest CML study ever conducted with Gleevec to be presented at ASCO
Nearly 15,500 patients in more than 80 countries have received Gleevec through patient assistance program
EAST HANOVER, N.J., May 10 (HSMN NewsFeed) -- Marking an important milestone since its first approval in May 2001, GleevecŪ (imatinib mesylate) tablets,* has become the first oncology drug to be validated as an effective and generally well-tolerated medicine that targets a specific cause of a cancer.
Gleevec was first approved in May 2001 by the US Food and Drug Administration (FDA) in an unprecedented 11 weeks -- the fastest FDA review period of any cancer drug at that time -- as a treatment for patients with advanced stage Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML).
Recent data marking 4.5 years of use showed that more than 90% of patients taking Gleevec continued to survive and were free from progressing to advanced disease. A five-year update from the IRIS study (International Randomized Interferon versus STI571), the largest clinical trial to date for newly diagnosed adult patients with Ph+ CML, will be presented at the American Society of Clinical Oncology meeting on June 3.
Before Gleevec was available, about 50% of patients progressed to the more advanced stages of Ph+ CML after only three to five years, and survival was generally short for those patients. Traditional, less-targeted treatments were associated with significant toxicities that often limited the ability of patients to stay on therapy long-term.
"Gleevec has an unprecedented record of efficacy and safety for the treatment of patients suffering from chronic myeloid leukemia, allowing many to resume their daily lives," said Dr. Daniel Vasella, Chairman and CEO of Novartis. "After more than a decade of research and clinical development as well as over 200,000 patient years of clinical treatment, we are moving forward with confidence in the principles of rational drug design pioneered with Gleevec. The success of Gleevec gives us confidence in the search for novel medicines that offer improved treatment outcomes."
No other drug for this disease has ever established such a proven and durable track record of efficacy and safety. Interim 54-month data from the IRIS study showed that approximately 93% of newly diagnosed patients with Ph+ CML treated with Gleevec had not progressed to the more advanced and terminal stages.
"What Gleevec tells us is that a precise understanding of what drives the growth of a particular cancer allows us to target those abnormalities specifically and develop an effective, durable and well-tolerated treatment," said Brian Druker, MD, JELD-WEN Chair of Leukemia Research at the Oregon Health and Science University Cancer Institute, Howard Hughes Medical Investigator and lead investigator of the key Gleevec clinical trials. "After five years, we know with certainty that going after the root cause of a cancer, and shutting it down, not only makes sense -- it works."
Gleevec is the first targeted therapy for patients with Ph+ CML since it has been proven to inhibit Bcr-Abl, the definitive cause of the disease. Following the rapid US approval on May 10, 2001, Gleevec was approved later that year in the European Union and subsequently in other countries worldwide. Gleevec has also been approved in the meantime for all phases of Ph+ CML.
After initial approval, Novartis led the industry in creating the Gleevec International Patient Assistance Program (GIPAP). Nearly 15,500 patients in more than 80 countries have received Gleevec under GIPAP and in the United States under the US Patient Assistance Program. These programs provide Gleevec, in accordance with the drug's specific approved use in countries, at no cost to qualified patients who are properly diagnosed, not insured, not reimbursed and have no other financial resources.
Novartis has continued to investigate Gleevec for use in treating patients with other types of cancer. In 2002, Gleevec was approved worldwide for the treatment of patients with unresectable and/or metastatic Kit (CD117)-positive gastrointestinal stromal tumors (GISTs).
In 2005, Gleevec was also submitted in the US and EU as a treatment for the solid tumor dermatofibrosarcoma protuberans and certain forms of myeloproliferative disorders as well as for the treatment of adult patients with Ph+ acute lymphoblastic leukemia (ALL). This year, Novartis submitted additional applications for the use of Gleevec in treating two rare hematologic malignancies: hypereosinophilic syndrome and systemic mastocytosis. All five of these diseases are considered rare but may be life threatening and often have no approved treatments.
About Gleevec Tablets
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-alpha) therapy. Gleevec tablets are also indicated for the treatment of pediatric patients with Ph+ chronic phase CML whose disease has recurred after stem cell transplant or who are resistant to IFN-alpha therapy. There are no controlled trials in pediatric patients demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival. Gleevec tablets are also indicated for the treatment of patients with KIT (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors. The effectiveness of Gleevec is based on objective response rate. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.
Important Safety Information**
Severe (NCI Grades 3/4) neutropenia (3%-48%), anemia (<1%-42%), thrombocytopenia (<1%-33%), hemorrhage (1%-19%), fluid retention (eg, pleural effusion, pulmonary edema, and ascites (<1%-8%) and superficial edema (1%-6%), musculoskeletal pain (1%-9%), and hepatotoxicity (3%-8%) were reported among GleevecŪ recipients. 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, 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 foreign 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 300mg/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 enclosed 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 of Gleevec Tablets**
The majority of the approximately 1700 adult patients who received Gleevec in clinical studies experienced adverse events at some time, but most were mild to moderate in severity. The most frequently reported adverse events were superficial edema (58%-81%), nausea (47%-74%), diarrhea (39%-70%), muscle cramps (28%-62%), vomiting (21%-58%), rash (36%-53%), fatigue (30%-53%), musculoskeletal pain (30%-49%), and abdominal pain (30%-40%).***
Supportive care may help management of most mild-to-moderate adverse events so that 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 "unprecedented outcomes," "promise," "durable," "long-term use," "survival," or similar expressions, or by express or implied discussions regarding potential new indications for Gleevec or potential future sales of Gleevec, or regarding the long-term impact of a patient's use of Gleevec. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Gleevec to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Gleevec will be approved for any additional indications in any market. Nor can there be any guarantee regarding potential future sales of Gleevec. Neither can there be any guarantee regarding the long-term impact of a patient's use of Gleevec. In particular, management's expectations regarding commercialization of Gleevec could be affected by, among other things, additional analysis of Gleevec 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.
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 (NYSE: NVS ) -- 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 GlivecŪ (imatinib) outside the U.S.
** GleevecŪ (imatinib mesylate) tablets prescribing information. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2005.
*** Numbers indicate the range of percentages in 5 studies among adult patients with Ph-positive CML and KIT-positive GIST. For more detailed study information, please see the full prescribing information for Gleevec.
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