(1) U.S. FDA Grants Priority Review for Femara For New Indication as First Ever Post-Tamoxifen Treatment

U.S. FDA Grants Priority Review for Femara For New Indication as First Ever Post-Tamoxifen Treatment for Early Breast Cancer in Postmenopausal Women

- Agency expected to give decision before end of year

BASEL, Switzerland, June 29/PRNewswire-FirstCall/ --

Novartis Oncology announced today that itssupplementary New Drug Application for Femara(R) (letrozole) has been grantedpriority review by the U.S. Food and Drug Administration (FDA) for anindication in the extended adjuvant treatment of early breast cancer inpostmenopausal women who have completed standard adjuvant (post-surgery)tamoxifen therapy.

The FDA grants priority review to productsthat appear to represent a significant advance for serious orlife-threatening diseases. The application was filed at the end of April2004. The priority review establishes an action date no later than six monthsafter the filing date. Femara received its first approval for this newindication from the Mexican health authorities earlier this month. NovartisOncology has also submitted marketing applications for this new indication inthe European Union, Canada and Switzerland among other countries.

"We are pleased the FDA recognizes thepotential for Femara to fulfill an important unmet medical need ofpostmenopausal women to reduce their risk of recurrence of breast cancerfollowing completion of therapy with tamoxifen," said Diane Young, MD, vicepresident, global head, Clinical Development, Novartis Oncology.

In women with early breast cancer, adjuvant therapywith tamoxifen has not been shown to provide additional benefit after fiveyears and, traditionally, most women have not received treatment aftercompletion of adjuvant tamoxifen therapy. More than half of the recurrencesof breast cancer occur after the completion of standard adjuvant therapy withtamoxifen. Recurrence of breast cancer after initial treatment placespatients at greater risk of developing distant metastases and of dying of thedisease.

There is currently no post-tamoxifen therapy availablefor the approximately 100,000 women who complete tamoxifen therapy in theUnited States each year. Upon completion of tamoxifen therapy, many of thesewomen are potential candidates for treatment with Femara.

The filing for this new indication was basedon data from the landmark MA-17 trial. MA-17 is the first study that hasprovided clinical evidence to support the use of a medication, Femara, toreduce the risk of breast cancer recurrence during this extended adjuvant(post-tamoxifen) period. Coordinated by the National Cancer Institute ofCanada Clinical Trials Group at Queens University in Kingston, Ontario andsupported by Novartis, the MA-17 study evaluated extended adjuvant treatmentwith Femara vs. placebo in over 5,100 postmenopausal women with early breastcancer. Interim results from MA-17 received an expedited review from the NewEngland Journal of Medicine and were published in October 2003. Updatedresults of the study were presented earlier this month at the annual meetingof the American Society of Clinical Oncology held in New Orleans.

About Femara

Femara, an aromatase inhibitor, is an oral once-a-dayfirst-line treatment for postmenopausal women with hormone receptor positiveor hormone receptor unknown locally advanced or metastatic breast cancer. Itis also approved for the treatment of advanced breast cancer inpostmenopausal women with disease progression following antiestrogen therapy,and as neo-adjuvant (pre-operative) therapy. Femara is currently available inmore than 80 countries worldwide. Not all indications are available in everycountry.

Femara Contraindications and Adverse Events

In the interim MA-17 analysis, the most common adverse events were hotflashes, sweating, edema, hypercholesterolemia, headache, arthralgia,myalgia, fatigue, constipation and dizziness, in greater than 10% of patientsin either arm of the study. Of these, hot flashes, arthralgia, and myalgiawere more common in those receiving Femara than placebo (P<0.05). Vaginalbleeding was more common in those taking placebo (P=0.01). The MA-17researchers noted a trend toward newly diagnosed cases of osteoporosis inwomen taking Femara vs. placebo (5.7 vs. 4.5%; P=0.07) and, at two yearsthere was a mean decrease in bone mineral density in the hip from baseline ascompared to placebo (3.0 vs. 0.4%; P=0.048).

Femara is contraindicated in patients with knownhypersensitivity to Femara or any of its excipients. Femara is generally welltolerated and adverse reaction rates in the first-line study in which Femarawas compared with tamoxifen were similar with those seen in second-linestudies. The most commonly reported adverse events for Femara vs. tamoxifenwere bone pain (22% vs. 21%), hot flashes (19% vs. 16%), back pain (18% vs.

19%), nausea (17% vs. 17%), dyspnea or labored breathing (18% vs. 17%),arthralgia (16% vs. 15%), fatigue (13% vs. 13%), coughing (13% vs. 13%),constipation (10% vs. 11%), chest pain (6% vs. 6%) and headache (8% vs. 6%).

Femara may cause fetal harm when administered to pregnant women. Theincidence of peripheral thromboembolic events, cardiovascular events, andcerebrovascular events was 3-4% in each treatment arm.