Actualizado 20/09/2007 22:05 CET
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European Committee Issues Positive Opinion on Wyeth's TORISEL(TM) for Advanced Renal Cell Carcinoma (1)

COLLEGEVILLE, Pennsylvania, September 20 /PRNewswire/ --

-- European Committee Issues Negative Opinion on MYLOTARG(R) for Acute Myeloid Leukemia; Wyeth Plans to Appeal

Wyeth Pharmaceuticals, a division of Wyeth (NYSE: WYE), announced today that it has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Evaluation Agency (EMEA) for the approval of TORISEL(TM) (temsirolimus) as a first-line therapy for patients with advanced renal cell carcinoma (RCC) who have at least three of six prognostic risk factors. The CHMP's opinion for TORISEL will now be forwarded to the European Commission for final approval, anticipated in November 2007.

"The CHMP's positive opinion underscores the importance of TORISEL, which has been shown to extend median overall survival in patients with advanced kidney cancer when compared with interferon-alpha," says Robert R. Ruffolo, Ph.D., President, Wyeth Research. The expected European Commission approval for TORISEL will be its second major approval. The United States Food and Drug Administration granted TORISEL its first approval in May 2007.

TORISEL has an Orphan Medicinal Product designation in the European Union for the treatment of renal cell carcinoma. About 85,700 new cases of kidney cancer were diagnosed in Europe in 2002, according to estimates from the International Agency for Research on Cancer, and renal cell carcinoma accounts for about 85 percent of all kidney cancers.

The CHMP issued a negative opinion regarding the marketing authorization for MYLOTARG(R) (gemtuzumab ozogamicin) for re-induction treatment of CD33-positive acute myeloid leukemia (AML) adult patients in first relapse who are not candidates for other intensive re-induction chemotherapy regimens (e.g., high-dose ARA-C). Among reasons cited for its opinion, the CHMP said the three main clinical studies for MYLOTARG only showed a modest activity, since only a small proportion of the 277 patients enrolled achieved complete remission (where leukemia cells are no longer detected in the blood and are at very low levels in the bone marrow). In addition, the CHMP noted that there was no available information comparing the efficacy of MYLOTARG to other treatments. The CHMP also said it was difficult to judge the length of remission and effect on survival. Wyeth plans to request a re-examination of the negative opinion, in accordance with current European regulatory legislation.

"We believe that MYLOTARG is an important drug treatment for acute myeloid leukemia, and we will continue to work with the CHMP to address the committee's concerns and pursue a way forward," Dr. Ruffolo says. About 27,000 cases of AML will be diagnosed in the United Kingdom, France, Germany, Spain, Italy, the United States and Japan in 2008.

About TORISEL(TM) (temsirolimus)

TORISEL was approved by the U.S. Food and Drug Administration (FDA) in May 2007 for the treatment of advanced RCC.

TORISEL specifically inhibits the mTOR (mammalian target of rapamycin) kinase, an important regulator of cell proliferation, cell growth and cell survival. Inhibition of mTOR in treated cancer cells blocked the translation of genes that regulate the cell cycle. In in vitro studies using renal cancer cell lines, TORISEL inhibited the activity of mTOR and resulted in reduced levels of certain cell growth factors involved in the development of new blood vessels, such as vascular endothelial growth factor.

TORISEL U.S. Important Safety Information

Hypersensitivity reactions manifested by symptoms, including, but not limited to anaphylaxis, dyspnea, flushing, and chest pain have been observed with TORISEL.

Serum glucose, serum cholesterol, and triglycerides should be tested before and during treatment with TORISEL(TM) (temsirolimus).

The use of TORISEL is likely to result in hyperglycemia and hyperlipemia. This may result in the need for an increase in the dose of, or initiation of, insulin and/or oral hypoglycemic agent therapy and/or lipid-lowering agents, respectively.

The use of TORISEL may result in immunosuppression. Patients should be carefully observed for the occurrence of infections, including opportunistic infections.

Cases of interstitial lung disease, some resulting in death, have occurred. Some patients were asymptomatic and others presented with symptoms. Some patients required discontinuation of TORISEL and/or treatment with corticosteroids and/or antibiotics.

Cases of fatal bowel perforation occurred with TORISEL. These patients presented with fever, abdominal pain, metabolic acidosis, bloody stools, diarrhea, and/or acute abdomen.

Cases of rapidly progressive and sometimes fatal acute renal failure not clearly related to disease progression occurred in patients who received TORISEL.

Due to abnormal wound healing, use TORISEL with caution in the perioperative period.

Patients with central nervous system tumors (primary CNS tumor or metastases) and/or receiving anticoagulation therapy may be at an increased risk of developing intracerebral bleeding (including fatal outcomes) while receiving TORISEL(TM) (temsirolimus).

Live vaccinations and close contact with those who received live vaccines should be avoided.

Patients and their partners should be advised to avoid pregnancy throughout treatment and for 3 months after TORISEL therapy has stopped.

The most common (incidence greater than or equal to 30%) adverse reactions observed with TORISEL are: rash (47%), asthenia (51%), mucositis (41%), nausea (37%), edema (35%), and anorexia (32%). The most common laboratory abnormalities (incidence greater than or equal to 30%) are anemia (94%), hyperglycemia (89%), hyperlipemia (87%), hypertriglyceridemia (83%), elevated alkaline phosphatase (68%), elevated serum creatinine (57%), lymphopenia (53%), hypophosphatemia (49%), thrombocytopenia (40%), elevated AST (38%), and leukopenia (32%).

Most common grades 3/4 adverse events included asthenia (11%), dyspnea (9%), hemoglobin decreased (20%), lymphocytes decreased (16%), glucose increased (16%), phosphorus decreased (18%), and triglycerides increased (44%).

Strong inducers of CYP3A4/5 (eg, dexamethasone, rifampin) and strong inhibitors of CYP3A4 (eg, ketoconazole, atazanavir) may decrease and increase concentrations of the major metabolite of TORISEL, respectively. If alternatives cannot be used, dose modifications of TORISEL(TM) (temsirolimus) are recommended.

St. John's Wort may decrease TORISEL plasma concentrations, and grapefruit juice may increase plasma concentrations of the major metabolite of TORISEL, and therefore both should be avoided.

The combination of TORISEL and sunitinib resulted in dose-limiting toxicity.

Please see TORISEL full U.S. prescribing information at http://www.TORISEL.com.

About MYLOTARG

MYLOTARG is indicated in the United States for the treatment of patients with CD33-positive acute myeloid leukemia in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy. The safety and efficacy of MYLOTARG in patients with poor performance status and organ dysfunction has not been established.

The effectiveness of MYLOTARG is based on overall response rates. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival, compared to any other treatment.

MYLOTARG U.S. Important Safety Information

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