Video: Afinitor(R) Approved in US as First Treatment for Patients With Advanced Kidney...

Video: Afinitor(R) Approved in US as First Treatment for Patients With
Advanced Kidney Cancer After Failure of Either Sunitinib or Sorafenib

- Afinitor more than doubled time without tumor growth and reduced the risk of
disease progression or death by 67% compared with placebo

- Only once-daily oral cancer treatment to directly target mTOR, a protein
inside the cell that controls tumor cell division and blood vessel growth

- Phase III trials underway to explore potential of Afinitor in multiple
additional cancers

EAST HANOVER, N.J., March 30 /PRNewswire/ -- Novartis announced today that
Afinitor(R) (everolimus) tablets has been approved by the US Food and Drug
Administration (FDA) for patients with advanced renal cell carcinoma (RCC)
after failure of treatment with Sutent(R) (sunitinib)* or Nexavar(R)
(sorafenib)**.

To view the Multimedia News Release, go to:
http://www.prnewswire.com/mnr/novartis/36142

Prior to Afinitor, no other therapy has been studied in a Phase III trial in
this patient population where there is an important unmet medical need(1).
Sutent and Nexavar are commonly used as initial treatments for advanced
RCC(2).

The approval is based on data that showed Afinitor, when compared with
placebo, more than doubled the time without tumor growth or death in patients
with advanced kidney cancer (4.9 vs. 1.9 months) and reduced the risk of
disease progression or death by 67% (hazard ratio=0.33 with 95% confidence
interval 0.25 to 0.43; P<0.0001)(3). Furthermore, additional data show that
after 10 months of treatment with Afinitor, approximately 25% of patients
still had no tumor growth(1) ***.

"This approval provides a new and useful tool for treating advanced renal cell
cancer, representing an important step forward in managing this disease," said
Robert J. Motzer, MD, attending physician, Memorial Sloan-Kettering Cancer
Center, New York and principal investigator of the RECORD-1 trial, the basis
for FDA approval of Afinitor. "New treatment options are vital to help us
continue to offer patients with advanced kidney cancer new ways to battle
their difficult-to-treat disease. Based on clinical trial data, this option
should be considered when sunitinib or sorafenib fail."

In 2008, the FDA granted priority review status to Afinitor, previously known
as RAD001, based on its potential to fill an unmet medical need for patients
with advanced kidney cancer. Novartis has filed regulatory submissions in the
European Union, Switzerland and Japan, as well as with other regulatory
agencies globally(1).

Afinitor inhibits mTOR, a protein in the cancer cell that controls tumor cell
division and blood vessel growth. Preclinical and clinical data have
established the important role of mTOR in the development and progression of
several types of tumors(1).

"With this approval, we can now offer patients a targeted therapy proven to
fulfill an important unmet need in the treatment of advanced kidney cancer,"
said David Epstein, President and CEO, Novartis Oncology, Novartis Molecular
Diagnostics. "We continue to study Afinitor in kidney cancer, and through a
broad clinical program to explore its potential in many other tumor types."

About renal cell carcinoma
Renal cell carcinoma is often referred to as kidney cancer. Kidney cancer
accounts for approximately 2% of all new cancers(4). RCC is the most common
type of kidney cancer, with occurrence rates rising steadily around the world
due in part to smoking and obesity(5,6). It is estimated that about 54,000 new
cases of RCC developed in the US in 2008 and more than 13,000 people died from
the disease(7).

In RCC, cancer cells develop in the lining of the kidney's tubes and grow into
a tumor(8). If left untreated, the tumor can spread to neighboring lymph nodes
and eventually other organs(9).

RECORD-1 trial
The FDA regulatory filing for Afinitor was based on data from RECORD-1 (REnal
Cell cancer treatment with Oral RAD001 given Daily), the largest Phase III
clinical trial to study the effects of an oral mTOR inhibitor in advanced RCC
patients whose cancer progressed despite prior treatment with sunitinib,
sorafenib or both sequentially. In February 2008, based on a recommendation
from an independent data monitoring committee, Novartis stopped the trial
after interim results showed that patients receiving Afinitor experienced a
significant delay in cancer progressing or death compared with patients
receiving placebo(1).

This international, multi-center, randomized, double-blind trial involved 416
patients with advanced RCC whose cancer progressed despite prior treatment
with sunitinib, sorafenib or both sequentially. In addition, prior therapy
with bevacizumab, interferon alfa and interleukin-2 was allowed. Patients were
randomized to receive Afinitor (10 mg) daily or placebo, in conjunction with
best supportive care. The primary endpoint of the study was progression-free
survival, which was assessed via a blinded independent, central radiological
review(10).

About Afinitor
Afinitor is the first oral, daily therapy (5 mg and 10 mg tablets) to treat
advanced kidney cancer after failure of treatment with sunitinib or sorafenib.
In cancer cells, Afinitor continuously targets mTOR, a protein that acts as a
central regulator of tumor cell division, blood vessel growth and cell
metabolism. Afinitor is also being studied in multiple cancer types, including
neuroendocrine, breast, gastric and hepatocellular carcinoma (HCC), as well as
tuberous sclerosis complex (TSC) and non-Hodgkin's lymphoma(11).

The active ingredient in Afinitor 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 for use in the
US(1).

For more information on Afinitor, visit www.afinitor.com or call
1-888-4-AFINITOR. US patients who may be eligible for financial assistance can
learn about the AfiniTRAC(TM) reimbursement support program by contacting
1-888-5AfiniTRAC or visiting the website for Afinitor.

Important safety information
Afinitor is contraindicated in patients with hypersensitivity to everolimus,
to other rapamycin derivatives or to any of the excipients. Potentially
serious adverse reactions include non-infectious pneumonitis and infections
for which patients should be monitored carefully and treated as needed. In
addition, non-infectious pneumonitis may require temporary dose reduction
and/or interruption or discontinuation. Patients with systemic invasive fungal
infections should not receive Afinitor. Oral ulceration is a common side
effect with Afinitor. Renal function, blood glucose, lipids and hematological
parameters should be evaluated prior to the start of therapy with Afinitor and
periodically thereafter. Strong or moderate CYP3A4 or P-glycoprotein
inhibitors should be avoided. An increase in the dose of Afinitor is
recommended when co-administered with a strong CYP3A4 inducer. Live
vaccinations and close contact with those who have received live vaccines
should be avoided. Afinitor should not be used in patients with severe hepatic
impairment. Afinitor may cause fetal harm in pregnant women.

The most common adverse reactions (incidence greater than or equal to 30%)
were stomatitis, infections, asthenia, fatigue, cough and diarrhea. The most
common grade 3/4 adverse reactions (incidence greater than or equal to 3%)
were infections, dyspnea, fatigue, stomatitis, dehydration, pneumonitis,
abdominal pain and asthenia. The most common laboratory abnormalities
(incidence greater than or equal to 50%) were anemia, hypercholesterolemia,
hypertriglyceridemia, hyperglycemia, lymphopenia and increased creatinine. The
most common grade 3/4 laboratory abnormalities (incidence greater than or
equal to 3%) were lymphopenia, hyperglycemia, anemia, hypophosphatemia and
hypercholesterolemia. Deaths due to acute respiratory failure (0.7%),
infection (0.7%) and acute renal failure (0.4%) were observed for patients
receiving Afinitor.

Disclaimer
The foregoing release contains forward-looking statements that can be
identified by terminology such as "risk," "options," "potential," "continue to
study," "explore," "estimated," "can" or similar expressions, or by express or
implied discussions regarding potential new indications or labeling for
Afinitor, potential approvals of Afinitor in additional markets, or regarding
potential future revenues from Afinitor. You should not place undue reliance
on these statements. Such forward-looking statements reflect the current views
of the Company regarding future events, and involve known and unknown risks,
uncertainties and other factors that may cause actual results with Afinitor to
be materially different from any future results, performance or achievements
expressed or implied by such statements. There can be no guarantee that
Afinitor will be approved for sale in any additional markets. Neither can
there be any guarantee that Afinitor will be approved for any additional
indications or labeling in any market. Nor can there be any guarantee that
Afinitor will achieve any particular levels of revenue in the future. In
particular, management's expectations regarding Afinitor 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 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.

About Novartis
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, preventive vaccines, diagnostic tools, cost-saving generic
pharmaceuticals and consumer health products. Novartis is the only company
with leading positions in these areas. In 2008, the Group's continuing
operations achieved net sales of USD 41.5 billion and net income of USD 8.2
billion. Approximately USD 7.2 billion was invested in R&D activities
throughout the Group. Headquartered in Basel, Switzerland, Novartis Group
companies employ approximately 96,700 full-time-equivalent associates and
operate in more than 140 countries around the world. For more information,
please visit http://www.us.novartis.com.

References
1. Novartis data on file.
2. National Comprehensive Cancer Network. "NCCN Clinical Practice
Guidelines in Oncology: Kidney Cancer." Available at
http://www.nccn.org/professionals/physician_gls/PDF/kidney.pdf.
Accessed
March 2009.
3. Prescribing Information for Afinitor.
4. McLaughlin JK, et al. Epidemiologic aspects of renal cell carcinoma.
Semin Oncol. 2006;33(5):527-533.
5. American Cancer Society. "What Is Kidney Cancer (Adult) - Renal Cell
Carcinoma?" Available at

http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_is_kidney_cance
r_22.asp. Accessed March 2009.
6. Eisen, et. al. "Sorafenib for Older Patients with Renal Cell
Carcinoma." J. Natl Cancer Inst. 2008;100(20):1454-1463.
7. American Cancer Society. "What Are the Key Statistics for Kidney
Cancer?" Available at

http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_sta
tistics_for_kidney_cancer_22.asp?sitearea=. Accessed March 2009.
8. National Cancer Institute. "General Information About Renal Cell
Cancer." Available at
http://www.cancer.gov/cancertopics/pdq/treatment/renalcell/patient.
Accessed March 2009.
9. American Cancer Society. "How Is Kidney Cancer (Renal Cell
Carcinoma) Staged?" Available at
http://www.cancer.org/docroot/CRI/content/
CRI_2_4_3X_How_is_kidney_cancer_staged_22.asp?rnav=cri. Accessed March
2009.
10. Escudier, B. et al. Phase-3 randomized trial of everolimus (RAD001)
vs.
placebo in metastatic renal cell carcinoma. Presented at the European
Society for Medical Oncology (ESMO) 33rd Congress on September 16,
2008.

11. A service of the U.S. National Institutes of Health. Available at
http://clinicaltrials.gov/. Accessed March 2009.

Novartis Media Relations

Media only:

Denise Brashear
Novartis Oncology
P: +1 862 778 7336

Dana Kahn Cooper
P: +1 732 817 1800
F: +1 732 817 1834

Investors only:

Richard Jarvis
Novartis Corporation
P: +1 212 830 2433

* Sutent(R) is a registered trademark of Pfizer Inc.
** Nexavar(R) is a registered trademark of Bayer HealthCare Pharmaceuticals,
Inc. and Onyx Pharmaceuticals.
*** Data from RECORD-1 study findings presented at the 33rd European Society
for Medical Oncology Congress.

SOURCE Novartis Pharmaceuticals Corporation

Media only, Denise Brashear of Novartis Oncology, +1-862-778-7336, or Dana
Kahn Cooper, +1-732-817-1800, fax, +1-732-817-1834; or Investors only, Richard
Jarvis, Novartis Corporation, 1-212-830-2433