RAD001 Phase II Trial Results Positive in Patients with Advanced Gastric Cancer After Failure of One or More Prior Treatments

EAST HANOVER, N.J., January 13, 2009 /PRNewswire/ -- Data released today show RAD001 (also known as everolimus; proposed brand name Afinitor(R)) halted tumor growth in 55% of patients with advanced gastric cancer, a condition for which there are limited treatment options. In addition, 45% of patients in the study demonstrated some tumor shrinkage(1).

The data will be presented at the American Society of Clinical Oncology's 2009 Gastrointestinal Cancers Symposium on January 15.

The open label, single arm, multi-center Phase II study of 54 patients conducted in Japan, is designed to assess the efficacy and safety of RAD001 in patients with advanced gastric cancer whose disease progressed despite prior treatment. Patients enrolled in the trial were heavily pre-treated. All trial participants were from Japan and of Asian descent (1).

"There are very limited treatment options for patients who progressed despite the standard treatment for this aggressive cancer," said Atsushi Ohtsu, MD, PhD, Director, Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba, Japan. "The results from this study demonstrate that RAD001 has the potential to provide an effective new option for these patients."

A global Phase III clinical trial program to evaluate the efficacy and safety of RAD001 monotherapy in approximately 500 advanced gastric cancer patients will begin enrollment this year.

"Most advanced gastric cancer patients eventually stop responding to current therapies, demonstrating a considerable need for new treatment options," said Alessandro Riva, MD, Executive Vice President & Global Head of Development, Novartis Oncology. "Early data show RAD001 may benefit these patients and provides the rationale for additional studies. Novartis is committed to further exploring the potential of RAD001 for this hard to treat cancer, as well as studying its role in treating other tumor types."

Gastric cancer, commonly referred to as stomach cancer, was diagnosed in 21,500 Americans in 2008 and claimed the lives of more than 10,000 in the same time period(2). This cancer is highly prevalent among people of Asian descent, with more than half of all new cases occurring in East Asia(3). It is believed that the incidence is high among this population due in part to Helicobacter pylori infection and a diet high in smoked, salted or pickled foods. Among ethnicities in the US, Asians and Pacific Islanders have the highest mortality rates(4).

The proof-of-concept, Phase II study is designed to assess the efficacy and safety of RAD001 (10 mg) daily in patients with advanced gastric cancer (inoperable, recurrent or metastatic gastric cancer) whose disease progressed despite prior treatment. The primary endpoint of the study is to assess disease control rate (DCR). Secondary endpoints included assessment of objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), and to describe the safety profile of RAD001.

The average duration of therapy was 57 days. There was a DCR (complete response/partial response/stable disease) of 55% at eight weeks (95% Confidence Interval: 40.4 - 68.4%). Of the 53 patients evaluated for the study's primary endpoint, 29 patients (55%) had stable disease, 22 (41%) had progressive disease and 2 (4%) had an unknown response. The ORR was zero. The median PFS was 83 days (95% Confidence Interval: 50 - 91 days), with 29.6% of patients estimated to still be progression-free at four months. Median overall survival was not attained at the time of evaluation.

The most commonly reported adverse events (all grades; >10% patients) in the study included, stomatitis, anorexia, fatigue, rash, nausea, edema peripheral, thrombocytopenia, diarrhea, pruritus, anemia, dysgeusia, vomiting, pyrexia, pneumonitis, constipation and insomnia. Serious adverse events (grade 3 or 4; >3% of patients) included anemia, hyponatremia, raised liver function, fatigue, stomatitis, anorexia, hyperglycemia, hypophosphatemia, ileus and lymphopenia.

RAD001, an oral once-daily inhibitor of mTOR, is an investigational drug being studied in multiple tumor types. In cancer cells, RAD001 provides daily inhibition of mTOR, a protein that acts as a central regulator of tumor cell division, cell metabolism and blood vessel growth.

RAD001 is being studied in multiple cancer types including advanced kidney, breast and neuroendocrine tumors and lymphoma.Currently, RAD001 is under regulatory review in the US and Europe for the treatment of advanced renal cell carcinoma.

The safety and efficacy profile of RAD001 has not yet been established in oncologyand there is no guarantee that RAD001 will become commercially available for oncology indications. The active ingredient in RAD001 is everolimus, which is available in different dosage strengths under the trade name Certican(R) for the prevention of organ rejection in heart and kidney transplant recipients. Certican was first approved in the EU in 2003. Certican is not approved in the US.

The foregoing release contains forward-looking statements that can be identified by terminology such as "promising," "will," "potential," "may," "committed," "exploring," "believed," "estimated," "anticipated," or similar expressions, or by express or implied discussions regarding potential regulatory filings or marketing approvals for RAD001 or regarding potential future revenues from RAD001. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with RAD001 to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that RAD001 will be approved for sale for any oncology indication in any market. Nor can there be any guarantee that RAD001 will achieve any particular levels of revenue in the future. In particular, management's expectations regarding RAD001 could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; 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; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG'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 the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release 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 those in the cardiovascular, metabolic, cancer, organ transplantation, central nervous system, dermatological, GI and respiratory areas. 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 which provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs, innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas. In 2007, the Group's continuing operations (excluding divestments in 2007) achieved net sales of USD 38.1 billion and net income of USD 6.5 billion. Approximately USD 6.4 billion was invested in R&D activities throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 97,000 full-time associates and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com.

(1) Ohtsu, A et al. Multicenter phase II study of RAD001 for previously treated metastatic gastric cancer. Presented at the American Society of Clinical Oncology's 2009 Gastrointestinal Cancers Symposium, January 15, 2008.

(2) American Cancer Society. Detailed Guide: Stomach Cancer. Available at : http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_stomach_cancer_40.asp?rnav=cri. Accessed on December 23, 2008.

(3) Ohtsu, A. Chemotherapy for metastatic gastric cancer: past, present, and future. J Gastroenterol 2008; 43:256-264.

(4) American Cancer Society. Overview: Stomach Cancer. Available at: http://www.cancer.org/docroot/CRI/content/CRI_2_2_2X_What_causes_stomach_cancer_40.asp?sitearea=. Accessed on December 23, 2008.

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    Novartis Oncology                         Novartis Corporation
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    Dana Kahn Cooper
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CONTACT: Media only, Denise Brashear of Novartis Oncology,+1-862-778-7336, Fax, +1-917-453-2665 Dana Kahn Cooper for NovartisOncology, +1-732-817-1800, fax, +1-732-817-1834; Investors only, JillPozarek of Novartis Corporation, +1-212-830-2445

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Posted: January 2009

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