FDA Approves Elitek(R) (rasburicase) for Management of Plasma Uric Acid Levels in Adults with Leukemia, Lymphoma, and Solid Tumors Receiving Anti-Cancer Therapy

FDA Approves Elitek(R) (rasburicase) for Management of Plasma Uric Acid Levels
in Adults with Leukemia, Lymphoma, and Solid Tumors Receiving Anti-Cancer
Therapy
- Elitek is now approved to manage a potentially life-threatening complication
associated with anti-cancer treatment in adults -

BRIDGEWATER, N.J., Oct. 16 /PRNewswire-FirstCall/ -- Sanofi-aventis U.S.
announced that the U.S. Food and Drug Administration (FDA) has granted
marketing approval for Elitek® (rasburicase) to be used for the initial
management of plasma uric acid (PUA) levels in adult patients with leukemia,
lymphoma, and solid tumor malignancies who are receiving anti-cancer therapy
expected to result in tumor lysis syndrome (TLS) and subsequent elevations of
plasma uric acid.

Today's FDA approval was based on pivotal Phase 3 trial results which
demonstrated that Elitek significantly reduced PUA levels when compared to the
current standard of care (oral allopurinol) in adults with hematologic cancers
at risk for the potentially life-threatening complication of TLS. Patients
considered at high risk for TLS either had an elevated level of PUA
(hyperuricemia) due to a malignancy, or were diagnosed with a very aggressive
hematologic malignancy (leukemia or lymphoma).

"The approval of Elitek in adult patients with cancer now provides physicians
with an important new option for managing elevated plasma uric acid which
could result in tumor lysis syndrome, a potentially life-threatening
complication that can develop from anti-cancer therapy," said principal
investigator Dr. Jorge Cortes, Professor of Medicine and Deputy Chair,
Department of Leukemia at The University of Texas, M.D. Anderson Cancer
Center, in Houston, Texas.

Clinical TLS was defined by changes in at least two or more laboratory
parameters, namely hyperuricemia, hyperkalemia, hyperphosphatemia and
hypocalcemia, along with at least one of the following clinical events
occurring within 7 days of treatment: renal failure/injury, need for dialysis,
and/or serum creatinine increase greater than 1.5 x ULN, arrhythmia or seizure
(according to the Cairo-Bishop criteria).

"We are very proud that Elitek - which has already been shown to bring
significant treatment benefits to pediatric patients at risk of developing
this complication - has now been approved by the U.S. Food and Drug
Administration to help adult patients as well," said Dr. Paul Chew, Senior
Vice President, U.S. Chief Science Officer/Chief Medical Officer of
sanofi-aventis U.S. "This approval is also an example of sanofi-aventis'
commitment to further exploring our existing compounds and the potential
benefit they bring to patients with serious diseases, such as in the areas of
oncology and hematology."

Study Background
The primary objective of the multi-center, open-label, randomized, parallel
group comparative study was to compare the safety and the effectiveness of
three treatments (intravenous Elitek (rasburicase) alone daily for 5 days,
intravenous Elitek daily for day 1 to day 3 followed by oral allopurinol daily
for day 3 to day 5, and oral allopurinol alone daily for 5 days) in achieving
uric acid response rate. The daily dose of Elitek was 0.20 mg/kg, while that
of allopurinol was 300 mg. The PUA response rate was defined as the
proportion of patients with PUA levels less than or equal to 7.5 mg/dL from
day 3 to day 7 after initiation of treatment.

Results showed that among patients treated with Elitek alone or followed by
oral allopurinol, uric acid levels were less than or equal to 2.0 mg/dL in 96%
of patients (at 4 hours of the day 1 dose). There were no patients in either
Elitek group with documented failure to control uric acid. In patients
treated with Elitek alone (n=92), the PUA response rate was 87%, which was
higher than that seen with patients treated with oral allopurinol alone (n=91)
at 66% (p=0.0009), a statistically significant difference, or those treated
with the Elitek/oral allopurinol combination (n=92) at 78%. The Elitek versus
Elitek/oral allopurinol combination difference in PUA response rate was not
statistically significant.

Antihyperuricemic treatment was extended beyond five days in 4.4% of patients
treated with oral allopurinol alone and 6.5% of patients treated with the
Elitek/oral allopurinol combination, versus 0% of patients receiving Elitek
alone. Clinical TLS occurred in 3% of Elitek-treated patients, 3% of
Elitek/oral allopurinol-treated patients, and 4% of oral allopurinol-treated
patients.

Hypersensitivity reactions occurred in 4.3% of patients treated with Elitek
alone and 1.1% of patients treated with the Elitek/oral allopurinol
combination. Hypersensitivity reactions included arthralgia, injection site
irritation, peripheral edema, and rash. The most common Grade 3/4 related
adverse reactions regardless of relationship to study drug were sepsis (5.4% /
6.5% / 4.4%), hypophosphatemia (4.3% / 6.5% / 6.6%), anxiety (3.3% / 0% / 0%),
abdominal pain (3.3% / 4.3% / 2.2%), hyperbilirubinemia (3.3% / 2.2% / 4.4%)
and increased alanine aminotransferase (3.3% / 4.3% / 2.2%) in the Elitek,
Elitek/oral allopurinol and oral allopurinol arms, respectively. Of note, all
patients were receiving anti-cancer chemotherapy and/or biologic anti-cancer
agents for their primary disease. The following serious adverse reactions
occurred with a difference in incidence of greater than or equal to 2% in
patients receiving Elitek compared to patients receiving oral allopurinol:
pulmonary hemorrhage, respiratory failure, supraventricular arrhythmias,
ischemic coronary artery disorders, and abdominal and gastrointestinal
infections.

Based on the results of the above study, Elitek is now indicated at a daily
dose of 0.20 mg/kg intravenously for up to 5 days for the initial management
of plasma uric acid levels in adults with leukemia, lymphoma and solid tumors
receiving anti-cancer therapy expected to result in tumor lysis syndrome and
subsequent elevation of plasma uric acid.

About Elitek®
A recombinant urate oxidase enzyme, Elitek is the first recombinant uricolytic
agent approved in the U.S. to maintain PUA levels in patients receiving
anti-cancer therapy. Elitek rapidly catabolizes circulating uric acid into
allantoin, a highly soluble by-product that is easily excreted by the kidneys.
Elitek reduces circulating uric acid levels as soon as 4 hours after the
first dose. Elitek was initially approved by the U.S. FDA in 2002 to manage
PUA levels in pediatric patients receiving anti-cancer treatment and at risk
for TLS. Visit www.elitekinfo.com for more information about Elitek. Elitek®
is also commercially available under the brand name of Fasturtec® outside the
United States.

Elitek is indicated for the initial management of plasma uric acid levels in
pediatric and adult patients with leukemia, lymphoma, and solid tumor
malignancies who are receiving anti-cancer therapy expected to result in tumor
lysis syndrome and subsequent elevation of plasma uric acid. Elitek is
indicated for only a single course of treatment.

IMPORTANT SAFETY INFORMATION

Anaphylaxis: ELITEK can cause severe hypersensitivity reactions including
anaphylaxis. Immediately and permanently discontinue ELITEK in patients who
experience a serious hypersensitivity reaction.

Hemolysis: Do not administer ELITEK to patients with glucose-6-phosphate
dehydrogenase (G6PD) deficiency. Immediately and permanently discontinue
ELITEK in patients developing hemolysis. Screen patients at higher risk for
G6PD deficiency (e.g., patients of African or Mediterranean ancestry) prior to
starting ELITEK.

Methemoglobinemia: ELITEK can result in methemoglobinemia in some patients.
Immediately and permanently discontinue ELITEK in patients developing
methemoglobinemia.

Interference with Uric Acid Measurements: ELITEK enzymatically degrades uric
acid in blood samples left at room temperature. Collect blood samples in
pre-chilled tubes containing heparin and immediately immerse and maintain
sample in an ice water bath. Assay plasma samples within 4 hours of
collection.

Among the 347 (265 pediatric; 82 adult) patients for whom all adverse
reactions regardless of severity were assessed in Studies 1, 2 and 3, as well
as an uncontrolled safety trial, the most frequently observed adverse
reactions (incidence greater than or equal to 10%) were vomiting (50%), fever
(46%), nausea (27%), headache (26%), abdominal pain (20%), constipation (20%),
diarrhea (20%), mucositis (15%), and rash (13%).

Among the 275 adult patients in Study 4, hypersensitivity reactions occurred
in 4.3% of patients treated with ELITEK alone and 1.1% of patients treated
with the ELITEK/oral allopurinol combination. Hypersensitivity reactions
included arthralgia, injection site irritation, peripheral edema, and rash.
The most common Grade 3 or 4 adverse reactions regardless of relationship to
study drug in the 3 arms of Study 4 (ELITEK alone; ELITEK combined with oral
allopurinol; oral allopurinol alone) were sepsis (5.4%; 6.5%; 4.4%),
hypophosphatemia (4.3%; 6.5%; 6.6%), anxiety (3.3%; 0%; 0%), abdominal pain
(3.3%; 4.3%; 2.2%), hyperbilirubinemia (3.3%; 2.2%; 4.4%), and increased
alanine aminotransferase (3.3%; 4.3%; 2.2%), respectively.

The following serious adverse reactions occurred with a difference in
incidence of greater than or equal to 2% in patients receiving ELITEK compared
to patients receiving oral allopurinol in randomized studies (Study 1 and
Study 4): pulmonary hemorrhage, respiratory failure, supraventricular
arrhythmias, ischemic coronary artery disorders, and abdominal and
gastrointestinal infections.

For full prescribing information, including boxed WARNING, please visit
http://products.sanofi-aventis.us/elitek/elitek.html.

About Tumor Lysis Syndrome
Tumor lysis syndrome (TLS) is a metabolic complication that can result either
spontaneously or following treatment of certain types of rapidly-growing
cancers, particularly leukemia or lymphoma. The syndrome develops when a
particularly large volume of tumor cells are rapidly destroyed by treatment,
releasing their contents - including nucleic acids, which are then eventually
catabolized into uric acid - into the bloodstream. Elevated levels of plasma
uric acid (hyperuricemia) is a serious condition that can lead to kidney
impairment if not controlled. Prevalence of TLS varies among patients with
different types of cancer, but occurs more often with malignancies that are
particularly sensitive to anti-cancer therapy.

About sanofi-aventis
Sanofi-aventis U.S. is an affiliate of sanofi-aventis, a leading global
pharmaceutical company that discovers, develops and distributes therapeutic
solutions to help improve the lives of patients. Sanofi-aventis is listed in
Paris (EURONEXT: SAN) and in New York (NYSE: SNY). For more information,
visit: www.sanofi-aventis.us or www.sanofi-aventis.com.

Forward Looking Statements
This press release contains forward-looking statements as defined in the
Private Securities Litigation Reform Act of 1995, as amended. Forward-looking
statements are statements that are not historical facts. These statements
include financial projections and estimates and their underlying assumptions,
statements regarding plans, objectives, intentions and expectations with
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"estimates," "plans" and similar expressions. Although sanofi-aventis'
management believes that the expectations reflected in such forward-looking
statements are reasonable, investors are cautioned that forward-looking
information and statements are subject to various risks and uncertainties,
many of which are difficult to predict and generally beyond the control of
sanofi-aventis, that could cause actual results and developments to differ
materially from those expressed in, or implied or projected by, the
forward-looking information and statements. These risks and uncertainties
include those discussed or identified in the public filings with the SEC and
the AMF made by sanofi-aventis, including those listed under "Risk Factors"
and "Cautionary Statement Regarding Forward-Looking Statements" in
sanofi-aventis' annual report on Form 20-F for the year ended December 31,
2008. Other than as required by applicable law, sanofi-aventis does not
undertake any obligation to update or revise any forward-looking information
or statements.

US.RAS.09.09.009

Contact: Madeline Malia, sanofi-aventis U.S., (908) 981-5687,
madeline.malia@sanofi-aventis.com

SOURCE sanofi-aventis

Madeline Malia, sanofi-aventis U.S., +1-908-981-5687,
madeline.malia@sanofi-aventis.com