- Data Showed Overall Survival Benefit With TORISEL Regardless of
Nephrectomy Status; Additional Analysis Examined Specific Side Effects -
COLLEGEVILLE, Pa., May 31 /PRNewswire-FirstCall/ -- Wyeth
Pharmaceuticals, a division of Wyeth (NYSE: WYE), today announced results
of two new analyses of the pivotal study of the mTOR (mammalian target of
rapamycin) inhibitor TORISEL(R) (temsirolimus), the only renal cancer
therapy proven to extend median overall survival compared with
interferon-alpha in patients with advanced renal cell carcinoma (RCC).
These analyses, which are being presented at the 44th Annual Meeting of the
American Society of Clinical Oncology (ASCO) in Chicago, reaffirm the
efficacy and safety of TORISEL for the treatment of advanced RCC. TORISEL
is the only approved cancer therapy that specifically inhibits the mTOR
kinase, an important regulator of cell proliferation, cell growth and cell
survival.
RCC will account for approximately 85 percent of renal cancers. There
are an estimated 54,390 new cases of kidney and renal pelvis cancer
diagnosed in the United States each year, and about 40 percent of patients
have advanced disease at the time of diagnosis.
TORISEL was studied in a three-arm, phase 3 clinical trial of 626
patients with advanced RCC with three or more of six preselected prognostic
risk factors who had received no prior systemic therapy. Results of this
study demonstrated that TORISEL significantly increased median overall
survival by 49 percent compared with interferon-alpha (10.9 months [95% CI:
8.6, 12.7] vs. 7.3 months [6.1, 8.8], P=0.0078) (Hazard Ratio [95% CI] =
0.73 [0.58, 0.92]).
"In summary, these analyses provide clinicians with additional
information about the efficacy and safety of TORISEL for the treatment of
advanced RCC patients. Wyeth is committed to the continued exploration of
mTOR inhibition with TORISEL for the treatment of a variety of cancers,"
says Joseph S. Camardo, M.D., Senior Vice President, Global Medical
Affairs, Wyeth Pharmaceuticals.
Abstract 5050: Exploratory Analysis of the Influence of Nephrectomy
Status on Temsirolimus Efficacy in Patients With Advanced Renal Cell
Carcinoma and Poor-Risk Features
This retrospective subgroup analysis evaluated whether the nephrectomy
status (whether or not patients had undergone surgery for removal of the
affected kidney) of patients with advanced RCC enrolled in the pivotal
phase 3 study had an effect on the observed overall survival benefit of
TORISEL compared with interferon-alpha. Investigators determined that both
overall survival and progression-free survival were longer for patients
treated with TORISEL compared with those treated with interferon-alpha,
regardless of whether they had undergone nephrectomy. In addition, among
patients who had not undergone nephrectomy, more patients treated with
TORISEL showed reductions in the size of their primary kidney tumor than
those treated with interferon-alpha (58% vs. 31%).
Abstract 5116: Characterization of Hyperglycemia, Hypercholesterolemia
and Hyperlipidemia in Patients With Advanced Renal Cell Carcinoma Treated
With Temsirolimus or Interferon-Alpha
Another analysis presented at the ASCO meeting examined specific side
effects seen in the pivotal phase 3 study of TORISEL for advanced RCC,
including high levels of blood glucose (hyperglycemia), cholesterol
(hypercholesterolemia), and lipids (hyperlipidemia). More patients treated
with TORISEL, either with or without diabetes, developed hyperglycemia of
grade 2 or higher (P=0.002 for diabetic patients, P=0.001 for non-diabetic
patients), compared with those treated with interferon-alpha. TORISEL also
was associated with the development of hypercholesterolemia of grade 2 or
higher, compared with interferon-alpha (P=0.001), but there was not a
significant increase in hyperlipidemia versus interferon-alpha (P=0.675).
However, the development of hyperglycemia or hypercholesterolemia did not
have affect on overall survival or progression-free survival in this study.
The clinical data for TORISEL presented at the meeting represent only a
portion of the totality of the safety and efficacy data from the ongoing
clinical development of TORISEL.
About TORISEL
TORISEL is an mTOR inhibitor. 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 is approved for the treatment of advanced RCC in the United
States, European Union and other markets, based on results of a phase 3
clinical study that demonstrated that TORISEL improves overall survival for
patients with advanced RCC compared with interferon-alpha.
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.
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.
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 (e.g., dexamethasone, rifampin) and strong
inhibitors of CYP3A4 (e.g., ketoconazole, atazanavir) may decrease and
increase concentrations of the major metabolite of TORISEL, respectively.
If alternatives cannot be used, dose modifications of TORISEL 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 (Grade 3/4 erythematous maculopapular rash, and gout/cellulitis
requiring hospitalization).
Please see TORISEL full Prescribing Information at
http://www.TORISEL.com.
Wyeth Pharmaceuticals
Wyeth Pharmaceuticals, a division of Wyeth, has leading products in the
areas of women's health care, infectious disease, gastrointestinal health,
central nervous system, inflammation, transplantation, hemophilia,
oncology, vaccines and nutritional products.
Wyeth is one of the world's largest research-driven pharmaceutical and
health care products companies. It is a leader in the discovery,
development, manufacturing and marketing of pharmaceuticals, vaccines,
biotechnology products, nutritionals and non-prescription medicines that
improve the quality of life for people worldwide. The Company's major
divisions include Wyeth Pharmaceuticals, Wyeth Consumer Healthcare and Fort
Dodge Animal Health.
The statements in this press release that are not historical facts are
forward-looking statements that are subject to risks and uncertainties that
could cause actual results to differ materially from those expressed or
implied by such statements. These risks and uncertainties include, without
limitation, the inherent uncertainty of the timing and success of, and
expense associated with, research, development, regulatory approval and
commercialization of our products and pipeline products; government cost-
containment initiatives; restrictions on third-party payments for our
products; substantial competition in our industry, including from branded
and generic products; emerging data on our products and pipeline products;
the importance of strong performance from our principal products and our
anticipated new product introductions; the highly regulated nature of our
business; product liability, intellectual property and other litigation
risks and environmental liabilities; uncertainty regarding our intellectual
property rights and those of others; difficulties associated with, and
regulatory compliance with respect to, manufacturing of our products; risks
associated with our strategic relationships; economic conditions including
interest and currency exchange rate fluctuations; changes in generally
accepted accounting principles; trade buying patterns; the impact of
legislation and regulatory compliance; risks and uncertainties associated
with global operations and sales; and other risks and uncertainties,
including those detailed from time to time in our periodic reports filed
with the Securities and Exchange Commission, including our current reports
on Form 8-K, quarterly reports on Form 10-Q and annual report on Form 10-K,
particularly the discussion under the caption "Item 1A, Risk Factors" in
our Annual Report on Form 10-K for the year ended December 31, 2007, which
was filed with the Securities and Exchange Commission on February 29, 2008.
The forward-looking statements in this press release are qualified by these
risk factors. We assume no obligation to publicly update any
forward-looking statements, whether as a result of new information, future
developments or otherwise.
SOURCE Wyeth Pharmaceuticals
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Related links:
http://www.wyeth.com
http://www.TORISEL.com
CONTACT:
Media, Danielle Halstrom, +1-484-865-2020,
Mobile, +1-215-280-3898, or Doug Petkus, +1-973-660-5218, both of
Wyeth Pharmaceuticals, or Investors, Justin Victoria of Wyeth,
+1-973-660-5340
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