- Data Showed Overall Survival Benefit With TORISEL Regardless of Nephrectomy Status; Additional Analysis Examined Specific Side Effects - COLLEGEVILLE, Pa., May 31
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
