First Results of Major Study Show that Femara(R) Provides a Disease Fr

EAST HANOVER, N.J., Jan. 26 /PRNewswire-FirstCall/ -- Adjuvant use of Femara(R) (letrozole tablets) in postmenopausal women with hormone receptor- positive early breast cancer demonstrated a significant 19% reduction in risk of relapse (p=0.003); especially reducing the risk that the cancer would spread to other parts of the body (distant metastases) by 27%, compared with the reductions offered by tamoxifen (p=0.006) according to an independent, international study presented today by the International Breast Cancer Study Group. The data, from the Breast International Group (BIG) 1-98 trial, result from a head-to-head comparison of Femara with tamoxifen in more than 8,000 women treated at a median follow-up of 26 months.

The BIG 1-98 trial demonstrated a particularly strong disease free survival advantage for patients at the highest risk of breast cancer recurrence in the adjuvant (post-surgery) setting, such as those with node- positive early breast cancer (cancer that already spread to lymph nodes at the time of diagnosis), and those who have received prior chemotherapy. These women are more likely to develop distant metastases and, therefore, may be at greater risk of dying from their disease.

Disease free survival, the primary efficacy endpoint in this study, was defined as the time from randomization to recurrence (including recurrence restricted to the breast after breast conserving treatment, whichever occurred first), metastasis, appearance of a second primary tumor, or death from any cause.

"The biggest fear of women who have battled breast cancer is that their breast cancer might return," said PD Dr. Beat Thurlimann, MD, Scientific Secretary General, Therapy of Early Breast Cancer Senology Center of Eastern Switzerland, Kantonsspital, St. Gallen. "Convincing results from this very large study show that letrozole tablets help more women remain cancer free when compared to tamoxifen."

Study Details

Postmenopausal women with early breast cancer in 27 countries were enrolled in this Phase III, randomized, double-blind, controlled clinical trial, supported by Novartis.

There was a statistically significant reduction of 17% in the risk of systemic failure (the time from randomization to systemic recurrence, appearance of a second non-breast malignancy, or death without recurrence, whichever occurred first) (p=0.02). There was a 14% reduction in risk of death in favor of Femara that was not significant. Patients will continue to be monitored to track disease status, survival and long-term tolerability.

These positive data complement those of the landmark MA-17 trial for the use of Femara in the extended adjuvant setting. Femara is the only aromatase inhibitor shown to be effective in both the adjuvant and extended adjuvant settings. The term extended adjuvant describes the period following standard adjuvant treatment with tamoxifen. Femara is approved for extended adjuvant treatment of early breast cancer in 20 countries worldwide.

"This is exciting news for breast cancer patients and Novartis. Femara is the only hormonal therapy that has been shown to significantly reduce the risk of breast cancer recurrence in postmenopausal women with early breast cancer after standard tamoxifen therapy, known as the extended adjuvant setting. Now we have the first evidence that Femara also offers a significant disease free survival advantage over tamoxifen in the adjuvant setting in this population," said Diane Young, MD, Vice President and Global Head, Clinical Development, Novartis Oncology.

In this trial, patients treated with Femara had significant reductions in vaginal bleeding, hot flushes, and endometrial cancer when compared to tamoxifen. Hypercholesterolemia, grade 3-5 stroke and other cardiovascular events were more common in Femara. As expected with estrogen deprivation therapy, the number of women reporting new bone fractures to date was 5.8% on Femara and 4.1% on tamoxifen. Grade 3-5 thromboembolic events were more common in tamoxifen-treated patients. In patients whose breast cancer did not recur, more deaths due to stroke were reported in Femara treated patients than tamoxifen-treated patients (7 vs. 1) as were cardiac causes (26 vs. 13). These events, combined with all deaths from causes other than recurrence of breast cancer were not statistically significant. The median age of women who died without experiencing a previous cancer event was 70 years, compared with a median age of 61 years for all women in the study. Further analysis of these preliminary data is ongoing. In the interim, routine assessments of bone mineral density and cholesterol levels with active treatment when necessary should be considered. Overall, more patients in the study died on tamoxifen than Femara.

BIG 1-98 is the only clinical trial designed to incorporate both a head- to-head comparison of Femara with tamoxifen during the first five years following breast cancer surgery and a sequencing of both agents to determine the most effective approach to minimize the risk of recurrence. Patients were randomized to the following arms: tamoxifen for five years, Femara for five years, tamoxifen for two years followed by Femara for three years, and Femara for two years followed by tamoxifen for three years. Results from the ongoing arms of the study, which are expected to determine which treatment is more effective, monotherapy or sequential therapy, and if sequential therapy, which sequence is more effective, are expected in 2008.

About Femara

Femara, a leading, once-a-day oral aromatase inhibitor, is also indicated for first-line treatment of postmenopausal women with hormone receptor- positive or hormone receptor-unknown locally advanced or metastatic breast cancer and for the treatment of advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Novartis has filed in the European Union for the indication of extended adjuvant treatment of early breast cancer in postmenopausal women who have completed standard adjuvant (post-surgery) tamoxifen therapy. In addition to the U.S., this indication is now approved in the United Kingdom, Switzerland, Mexico, Korea and other countries around the world. Femara is currently available in more than 80 countries worldwide. Not all indications are available in every country.

Contraindications, warnings and adverse events

Side effects commonly reported with Femara are generally mild to moderate. In the extended adjuvant setting, those seen more often with Femara than with placebo are hot flashes (50% to 43%) arthralgia/arthritis (29% vs. 23%) and myalgia (7% vs. 5%). In a clinical trial, osteoporosis was reported more frequently with Femara than with placebo (7% vs. 6%). During treatment, both arms of the trial showed expected modest decreases in bone mineral density in the hip and spine.

Femara may cause fetal harm when administered to pregnant women. You should not take Femara if you are allergic to Femara or any of its ingredients.

The foregoing release contains forward-looking statements that can be identified by terminology such as "will file," "first," "only," "significant advantage," "helps," "benefit," or similar expressions, or by express or implied discussions regarding potential future sales of Femara. Such forward- looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Femara to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Femara will reach any particular sales levels. In particular, management's expectations regarding commercialization of Femara could be affected by, among other things, additional analysis of Femara 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; increased 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 U.S. 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 the information in this press release as of this date and does not undertake any obligation to update any forwardlooking statements contained in this press release as a result of new information, future events or otherwise.

For more information

Patients interested in more information regarding Femara can contact the Novartis toll-free number 1-866-4FEMARA or the websites, http://www.us.femara.com/ or http://www.us.novartisoncology.com/, please see full prescribing information.

Reporters interested in more information regarding Femara or Novartis Oncology can visit the Novartis Oncology Virtual Press Office at http://www.novartisoncologyvpo.com/. The site features background information on Novartis Oncology products.

About Novartis

Novartis Oncology is a business unit within Novartis AG , a world leader in pharmaceuticals and consumer health. In 2004, the Group's businesses achieved sales of USD 28.2 billion and a net income of USD 5.8 billion. The Group invested approximately USD 4.2 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 81,400 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com/.

Contacts Media Only: Investors Only: Kim Fox Jill Pozarek Novartis Oncology Novartis Corporation P: 973-960-7532 P: 1 212-830-2445 Dana Kahn Cooper P: 1 732-817-1800 F: 1 732-817-1834 Leslie Wheeler P: +1-646-331-4062 P: +1-917-254-0033