- Data From Phase 3 Study Presented at ASCO -
COLLEGEVILLE, Pa., May 31 /PRNewswire-FirstCall/ -- Wyeth
Pharmaceuticals, a division of Wyeth (NYSE: WYE), today announced results
of a three-arm phase 3 clinical trial that show patients with relapsed
and/or refractory mantle cell lymphoma (MCL), a form of non-Hodgkin's
lymphoma, treated with the mTOR (mammalian target of rapamycin) inhibitor
TORISEL(R) (temsirolimus) experienced a statistically significant
improvement in median progression-free survival (PFS), compared with
single-agent therapy selected by the investigator (4.8 months vs. 1.9
months, P=0.0009). These results are being presented at the 44th Annual
Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
"Relapsed/refractory mantle cell lymphoma is extremely difficult to
treat, and this is the first comparative phase 3 study to show a
significant improvement in progression-free survival for these patients,"
says Georg Hess, M.D., Johannes Gutenberg-Universitat, Mainz, Germany.
"These data further support the antitumor activity seen in phase 2 studies
of temsirolimus in relapsed/refractory mantle cell lymphoma and indicate
that mTOR inhibition may be a viable approach in this disease area."
MCL accounts for approximately 6 percent of non-Hodgkin's lymphoma
cases.
"These findings reinforce the clinical potential of mTOR inhibition
with TORISEL. 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.
TORISEL was approved in May 2007 for the treatment of advanced renal
cell carcinoma (RCC) and is the only mTOR inhibitor approved to treat RCC.
TORISEL specifically inhibits the mTOR kinase, an important regulator of
cell proliferation, cell growth and cell survival and is the only renal
cancer therapy proven to extend median overall survival compared with
interferon-alpha in patients with advanced RCC.
Study Design and Results
This three-arm, open-label, randomized, phase 3 trial compared two
different dose regimens of TORISEL with investigators' choice of therapy
(IC) in patients with relapsed or refractory MCL who had received two to
seven prior therapies, which could include hematopoietic stem cell
transplantation. Patients were randomly assigned to receive intravenous
(IV) TORISEL at 175 mg for three successive weekly doses followed by 75 mg
IV weekly; TORISEL 175 mg IV for three successive weekly doses followed by
25 mg IV weekly; or investigators' choice of one of the following single
agents at predefined doses: gemcitabine, fludarabine, chlorambucil,
cladribine, etoposide, cyclophosphamide, thalidomide, vinblastine,
alemtuzumab or lenalinomide. The primary end point was PFS based on
independent review. Secondary end points were objective response rate and
overall survival.
Median PFS for patients treated with TORISEL 175 mg/75 mg was 4.8
months, compared with 1.9 months for patients treated with IC. In the
TORISEL 175 mg/25 mg arm, median PFS was 3.4 months, but this difference
was not statistically different from IC (P=0.0618).
Patients receiving TORISEL 175 mg/75 mg showed a nonsignificant trend
toward longer overall survival than those treated with IC (13.6 months vs.
9.7 months; HR=0.80). TORISEL 175 mg/75 mg led to a statistically
significant improvement over IC in objective response rates (22 percent vs.
2 percent, P=0.0019).
The most frequently occurring grade 3 or 4 adverse events among
patients treated with TORISEL 175 mg/75 mg, TORISEL 175 mg/25 mg, or IC
were thrombocytopenia (59 percent vs. 52 percent vs. 36 percent of
patients, respectively), anemia (20 percent vs. 11 percent vs. 17 percent),
neutropenia (15 percent vs. 22 percent vs. 26 percent) and asthenia (13
percent vs. 19 percent vs. 8 percent).
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.
An application for the use of TORISEL for the treatment of relapsed
and/or refractory MCL is currently under review with the European Medicines
Agency (EMEA). TORISEL received Orphan Medicinal Product designation for
the treatment of MCL in the European Union in November 2006.
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:
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CONTACT:
Media, Danielle Halstrom, +1-484-865-2020, or
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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