FDA Approves New Taxotere® (docetaxel) Injection Concentrate Formulation

- 1-vial Taxotere offers simplified preparation -

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Aug 05, 2010, 08:00 ET

BRIDGEWATER, N.J., Aug. 5 /PRNewswire/ -- Sanofi-aventis U.S. announced today that the U.S. Food and Drug Administration (FDA) has approved a new one-vial formulation of its chemotherapeutic agent Taxotere® (docetaxel) Injection Concentrate. The 1-vial Taxotere is anticipated to become available to cancer treatment clinics and hospitals nationwide in the fall in both 80 mg and 20 mg dosages.

Introduced more than 14 years ago, Taxotere is approved by the FDA for use in treating patients at specific stages of 5 types of cancer: metastatic and adjuvant breast cancer, metastatic androgen independent prostate cancer, advanced non-small cell lung cancer, advanced gastric adenocarcinoma and locally advanced squamous cell carcinoma of the head and neck.

"This new formulation underscores the commitment sanofi-aventis has made to Taxotere and to healthcare professionals. We look forward to adding this formulation of Taxotere to the arsenal of oncology products sanofi-aventis offers to the cancer community," said Paul Hawthorne, Vice President and Head of the Oncology Business Unit at sanofi-aventis U.S.

The most common adverse reactions across all Taxotere® indications are infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions and myalgia.

Previously, Taxotere was available to health care professionals in a two vial formulation – one vial containing docetaxel concentrate and the other with the diluent. The 1-vial Taxotere eliminates the need for the initial dilution step with the diluent. The 1-vial Taxotere, now at 20mg/ml concentration, is ready to be added directly into the infusion solution. The new 1-vial Taxotere is expected to help simplify preparation by eliminating the dilution step.

With 1-vial Taxotere, the pharmaceutical ingredients of Taxotere and the one hour IV infusion administration to the patient remain the same.

Taxotere has been used worldwide to treat more than 1.5 million patients, 100,000 of whom were participants in clinical trials.

Important Safety Information for Taxotere (docetaxel) Injection Concentrate

WARNING

The incidence of treatment-related mortality associated with Taxotere® therapy is increased in patients
with abnormal liver function, in patients receiving higher doses, and in patients with non-small cell lung
carcinoma and a history of prior treatment with platinum-based chemotherapy who receive Taxotere® as
a single agent at a dose of 100 mg/m(2)
Taxotere® should not be given to patients with bilirubin > upper limit of normal (ULN), or to patients with
AST and/or ALT > 1.5 X ULN concomitant with alkaline phosphatase > 2.5 X ULN
- Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline
  phosphatase are at increased risk for the development of grade 4 neutropenia, febrile neutropenia,
  infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death
- Patients with isolated elevations of transaminase > 1.5 X ULN also had a higher rate of febrile
  neutropenia grade 4 but did not have an increased incidence of toxic death
- Bilirubin, AST or ALT, and alkaline phosphatase values should be obtained prior to each cycle of
  Taxotere® therapy
Taxotere® therapy should not be given to patients with neutrophil counts of < 1500 cells/mm(3)
- In order to monitor the occurrence of neutropenia, which may be severe and result in infection,
  frequent blood-cell counts should be performed on all patients receiving Taxotere®
Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or
bronchospasm, or very rarely fatal anaphylaxis, have been reported in patients who received a 3-day
dexamethasone premedication
- Hypersensitivity reactions require immediate discontinuation of Taxotere® infusion and
  administration of appropriate therapy
Taxotere® must not be given to patients who have a history of severe hypersensitivity reactions to
Taxotere® or to other drugs formulated with polysorbate 80
Severe fluid retention occurred in 6.5% (6/92) of patients despite use of a 3-day dexamethasone
premedication regimen. It was characterized by one or more of the following events: poorly tolerated
peripheral edema, generalized edema, pleural effusion requiring urgent drainage, dyspnea at rest,
cardiac tamponade, or pronounced abdominal distention (due to ascites).

Neutropenia (<2,000 neutrophils/mm(3)) occurs in virtually all patients given 60-100 mg/m(2) of Taxotere® and grade 4 neutropenia (<500 cells/mm(3)) occurs in 85% of patients given 100 mg/m(2) and 75% of patients given 60 mg/m(2)

Patients should be premedicated with oral corticosteroids prior to each Taxotere® administration to reduce the incidence and severity of fluid retention. Patients with pre-existing effusions should be closely monitored from the first dose for possible exacerbation of the effusions

Treatment-related acute myeloid leukemia (AML) or myelodysplasia has occurred in patients given anthracyclines and/or cyclophosphamide, including use with Taxotere® in adjuvant therapy of breast cancer

Localized erythema of the extremities with edema followed by desquamation has been observed

In case of severe skin toxicity, an adjustment in dosage is recommended

Severe neurosensory symptoms (e.g. paresthesia, dysesthesia, pain) were observed in 5.5% (53/965) of metastatic breast cancer patients, and resulted in treatment discontinuation in 6.1%

When these symptoms occur, dosage must be adjusted; if symptoms persist, treatment should be discontinued

Severe asthenia was reported in 14.9% (144/965) of metastatic breast cancer patients, but led to treatment discontinuation in only 1.8%

Symptoms of fatigue and weakness may last a few days up to several weeks and may be associated with deterioration of performance status in patients with progressive disease

Taxotere® can cause fetal harm when administered to pregnant women. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Taxotere®

The most common adverse reactions across all Taxotere® indications are infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions and myalgia

In patients treated with TCF for gastric cancer, the incidence of serious adverse events was higher in patients greater than or equal to 65 years than in younger patients. Adverse events (all grades) occurring at rates greater than or equal to 10% higher in elderly patients included lethargy, stomatitis, diarrhea, dizziness, edema, and febrile neutropenia/neutropenic infection

Taxotere® should be administered in a facility equipped to manage possible complications (e.g. anaphylaxis)

About Taxotere

Taxotere is approved for the following indications:

Breast Cancer	TAXOTERE is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy TAXOTERE in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer
Non-Small Cell Lung Cancer	TAXOTERE as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy TAXOTERE in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer who have not previously received treatment
Prostate Cancer	TAXOTERE in combination with prednisone is indicated for the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer
Gastric Adenocarcinoma	TAXOTERE in combination with cisplatin and fluorouracil is indicated for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior treatment
Head and Neck Cancer	TAXOTERE in combination with cisplatin and fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)

For more information about Taxotere, including full prescribing information and product boxed WARNING, visit: http://products.sanofi-aventis.us/taxotere/taxotere_1Vial.pdf

Sanofi-aventis Oncology

Formed in March 2010, sanofi-aventis Oncology is targeting cancer on all fronts in an effort to address unmet medical needs for a broad range of patients. Starting with a deep understanding of the mechanisms by which cancer develops, grows and spreads as well as identifying the right science early in the discovery process, the company employs innovative approaches to bring the right medicines to the right patients.

There are currently more than 10 compounds in development across a broad scientific platform, including cytotoxic, antimitotic, anti-angiogenic agents, antivascular agents, monoclonal antibodies and cancer vaccines, as well as supportive care therapies. Four of these compounds are now being investigated in phase 3 clinical studies aimed at multiple solid and hematologic tumors.

About sanofi-aventis

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

Sanofi-aventis U.S. offers reimbursement support services and patient assistance programs through our PACT+ program to help provide eligible patients in financial need with access to therapies prescribed by their healthcare professionals. For more information, please call 1-800-996-6626.

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 projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words "expects," "anticipates," "believes," "intends," "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 among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such products candidates, the absence of guarantee that the products candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives, the Group's ability to benefit from external growth opportunities as well as 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, 2009. Other than as required by applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.

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