BRIDGEWATER, N.J., Oct. 1 /PRNewswire-FirstCall/ -- Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced today that data from the Phase III TROPIC study, which was the basis for the June 2010 U.S. Food and Drug Administration (FDA) approval of Jevtana® (cabazitaxel) Injection, was published in the October 2, 2010 print edition of The Lancet in an article titled "Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial." The data demonstrated that Jevtana in combination with prednisone reduced the risk of death by 30% in men with metastatic castration-resistant prostate cancer (also known as metastatic hormone refractory prostate cancer, or mHRPC) whose disease progressed following treatment with a docetaxel-containing treatment regimen.
"Jevtana is the first approved therapy to fill a critical gap among patients with the most advanced stage of prostate cancer and is the first therapeutic option for these patients shown to prolong survival," said Oliver Sartor, M.D., Piltz Professor for Cancer Research at Tulane Medical School, New Orleans, and North American principal investigator for the pivotal TROPIC trial.
"Sanofi-aventis Oncology is tackling cancer on all fronts to provide new solutions that make a difference in patients' lives," said Debasish Roychowdhury, M.D., Senior Vice President, Head of Global Oncology, sanofi-aventis. "The publication of this pivotal trial in The Lancet underscores the importance of the study, which is the first to demonstrate an overall survival advantage in patients with metastatic hormone refractory prostate cancer whose disease has progressed following treatment with a docetaxel-containing treatment regimen."
Results of the TROPIC study showed that the combination of Jevtana and prednisone significantly reduced the risk of death by 30% [HR=0.70 (95% CI: 0.59-0.83); P<0.0001], with an improvement in median overall survival of 15.1 months versus 12.7 months in the mitoxantrone combination arm. In addition, patients in the Jevtana combination arm showed a significantly higher rate of investigator-assessed tumor response (14.4 [95% CI: 9.6-19.3; P<0.001]) compared with those in the mitoxantrone combination arm (4.4 [95% CI: 1.6-7.2; P<0.001]).
In the TROPIC study, the most common (greater than or equal to 10%) adverse reactions (grade 1-4) were neutropenia, anemia, leukopenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysguesia, cough, arthralgia, and alopecia.
The most common (greater than or equal to 5%) grade 3-4 adverse reactions in patients who received Jevtana were neutropenia, leukopenia, anemia, febrile neutropenia, diarrhea, fatigue, and asthenia. The most common adverse reactions leading to treatment discontinuation in the Jevtana group were neutropenia and renal failure. Treatment discontinuations due to adverse drug reactions occurred in 18% of patients who received Jevtana and 8% of patients who received mitoxantrone. Deaths due to causes other than disease progression within 30 days of last study drug dose were reported in 18 (5%) Jevtana patients and 3 (less than 1%) mitoxantrone-treated patients. The most common fatal adverse reactions in Jevtana patients were infections (n=5) and renal failure (n=4). One death was due to diarrhea-induced dehydration and electrolyte imbalance.
About the TROPIC Trial
TROPIC was conducted in 146 trial sites in 26 countries, including the U.S. This multicenter, Phase III, randomized registrational trial assessed 755 mCRPC patients whose disease had progressed following treatment with docetaxel-based chemotherapy.
Patients were randomly assigned to receive cabazitaxel plus prednisone/prednisolone or mitoxantrone plus prednisone/prednisolone (378 and 377 patients, respectively), for up to a maximum of 10 cycles. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, tumor response rate, tumor progression, prostate-specific antigen (PSA) response, PSA progression, pain response, and pain progression. Disease progression was defined as tumor progression, PSA progression or pain progression. Other secondary endpoints were overall safety of cabazitaxel in combination with prednisone, pharmacokinetics of cabazitaxel and its metabolite in this patient population, and the effect of prednisone on the pharmacokinetics of cabazitaxel.
About Jevtana® (cabazitaxel) Injection
Jevtana, a microtubule inhibitor, is approved in combination with prednisone for the treatment of patients with metastatic hormone refractory prostate cancer (mHRPC) previously treated with a docetaxel-based treatment regimen. Jevtana is to be administered intravenously. Jevtana was granted fast track designation by the FDA in November 2009. The rolling new drug application (NDA) submission was completed in March 2010 and was granted priority review in April 2010; Jevtana was approved by the FDA less than three months later. A registration dossier of Jevtana is also under regulatory review by other regulatory authorities, including the European Medicines Agency.
Important Safety Information for Jevtana
WARNING
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CONTRAINDICATIONS
- JEVTANA should not be used in patients with neutrophil counts of less than or equal to 1,500/mm(3).
- JEVTANA is contraindicated in patients who have a history of severe hypersensitivity reactions to cabazitaxel or to other drugs formulated with polysorbate 80.
WARNINGS AND PRECAUTIONS
- Neutropenic deaths have been reported
- Monitor blood counts frequently to determine if initiation of G-CSF and/or dosage modification is needed
- Primary prophylaxis with G-CSF should be considered in patients with high-risk clinical features
- Severe hypersensitivity reactions can occur
- Premedicate with corticosteroids and H2 antagonists
- Discontinue infusion immediately if hypersensitivity is observed and treat as indicated
- Mortality related to diarrhea has been reported
- Rehydrate and treat with anti-emetics and anti-diarrheals as needed
- If experiencing grade greater than or equal to 3 diarrhea, dosage should be modified
- Renal failure, including cases with fatal outcomes, has been reported. Identify cause and manage aggressively.
- Patients greater than or equal to 65 years of age were more likely to experience fatal outcomes not related to disease progression and certain adverse reactions, including neutropenia and febrile neutropenia. Monitor closely.
- Patients with impaired hepatic function were excluded from the randomized clinical trial
- Hepatic impairment is likely to increase the JEVTANA® concentrations
- JEVTANA® should not be given to patients with hepatic impairment
- JEVTANA® can cause fetal harm when administered to a pregnant woman
- There are no adequate and well-controlled studies in pregnant women using JEVTANA®
ADVERSE REACTIONS
- Deaths due to causes other than disease progression within 30 days of last study drug dose were reported in 18 (5%) JEVTANA®-treated patients. The most common fatal adverse reactions in JEVTANA®-treated patients were infections (n=5) and renal failure (n=4)
- The most common (greater than or equal to 10%) grade 1–4 adverse reactions were anemia, leukopenia, neutropenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysgeusia, cough, arthralgia, and alopecia
- The most common (greater than or equal to 5%) grade 3–4 adverse reactions in patients who received JEVTANA® were neutropenia, leukopenia, anemia, febrile neutropenia, diarrhea, fatigue, and asthenia
Please see the accompanying full prescribing information for Jevtana, including boxed WARNING, or visit http://products.sanofi-aventis.us/jevtana/jevtana.pdf
The Incidence of Prostate Cancer
Worldwide, prostate cancer ranks third in cancer incidence and sixth in cancer mortality in men. In the U.S., prostate cancer remains the second most common cause of cancer death among men after lung cancer. In 2009, an estimated 192,000 new cases were anticipated in the U.S., while 27,000 men were expected to have died from the disease. For many patients with prostate cancer, their disease continues to progress despite prior treatment – including surgical and/or hormonal castration followed by chemotherapy. Metastatic prostate cancer indicates that the cancer has spread to the lymph nodes or other parts of the body, particularly the bones. Castration resistant/hormone-refractory prostate cancer means that the cancer has continued to grow despite the suppression of male hormones that fuel the growth of prostate cancer cells. An estimated 10-20% of patients with prostate cancer are diagnosed when the cancer has already metastasized.
About 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 III clinical studies aimed at multiple solid and hematologic tumors.
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 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.
US.CAB.10.09.022
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