Five years after approval, Gleevec underscores the promise of targeted therapy to provide sustained disease control

Posted by rob on May 12, 2006 under Uncategorized | Be the First to Comment

EDIA RELEASE

Five years after approval, Gleevec underscores the promise of targeted

therapy to provide sustained disease control

• Unprecedented 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, May 10, 2006 – Marking an important milestone since its first approval in

May 2001, Gleevec® (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

? Known as Glivec® (imatinib) outside the U.S.

1/5

2/5

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-?) 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-? 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.

3/5

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 Gleevec® 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.

* Gleevec® (imatinib mesylate) tablets prescribing information. East Hanover, NJ: Novartis

Pharmaceuticals Corporation; 2005.

4/5

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.

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 (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

* Gleevec® (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 Phpositive

CML and KIT-positive GIST. For more detailed study information, please see the full

prescribing information for Gleevec.

5/5

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.

# # #

Contacts

John Gilardi

Novartis Global Media Relations

Tel +41 61 324 3018

Mobile +41 79 596 1408

John.Gilardi@novartis.com

Geoff Cook

Novartis Oncology

Tel +1 862 778 2675 (direct)

Geoffrey.Cook@novartis.com