Collegeville, Pennsylvania (ots/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
"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
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
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
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
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
Please see TORISEL full U.S. prescribing information at
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
WARNINGS: MYLOTARG should be administered under the supervision of
physicians experienced in the treatment of acute leukemia and in
facilities equipped to monitor and treat leukemia patients. There are
no controlled trials demonstrating efficacy and safety using MYLOTARG
in combination with other chemotherapeutic agents. Therefore,
MYLOTARG should only be used as single agent chemotherapy and not in
combination chemotherapy regimens outside clinical trials. Severe
myelosuppression occurs when MYLOTARG is used at recommended doses.
HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS, INFUSION
REACTIONS, PULMONARY EVENTS: MYLOTARG administration can result in
severe hypersensitivity reactions (including anaphylaxis), and other
infusion-related reactions which may include severe pulmonary events.
Infrequently, hypersensitivity reactions and pulmonary events have
been fatal. In most cases, infusion-related symptoms occurred during
the infusion or within 24 hours of administration of MYLOTARG and
resolved. MYLOTARG infusion should be interrupted for patients
experiencing dyspnea or clinically significant hypotension. Patients
should be monitored until signs and symptoms completely resolve.
Discontinuation of MYLOTARG(R) (gemtuzumab ozogamicin) treatment
should be strongly considered for patients who develop anaphylaxis,
pulmonary edema, or acute respiratory distress syndrome. Since
patients with high peripheral blast counts may be at greater risk for
pulmonary events and tumor lysis syndrome, physicians should consider
leukoreduction with hydroxyurea or leukapheresis to reduce the
peripheral white count to below 30,000/microL prior to administration
of MYLOTARG. (See WARNINGS.)
HEPATOTOXICITY: Hepatotoxicity, including severe hepatic
veno-occlusive disease (VOD), has been reported in association with
the use of MYLOTARG as a single agent, as part of a combination
chemotherapy regimen, and in patients without a history of liver
disease or hematopoietic stem-cell transplant (HSCT). Patients who
receive MYLOTARG either before or after HSCT, patients with
underlying hepatic disease or abnormal liver function, and patients
receiving MYLOTARG in combinations with other chemotherapy are at
increased risk for developing VOD, including severe VOD. Death from
liver failure and from VOD has been reported in patients who received
MYLOTARG. Physicians should monitor their patients carefully for
symptoms of hepatotoxicity, particularly VOD. These symptoms can
include: rapid weight gain, right upper quadrant pain, hepatomegaly,
ascites, elevations in bilirubin and/or liver enzymes. However,
careful monitoring may not identify all patients at risk or prevent
the complications of hepatotoxicity. (See WARNINGS and ADVERSE
MYLOTARG(R) (gemtuzumab ozogamicin) is contraindicated in patients
with a known hypersensitivity to gemtuzumab ozogamicin or any of its
components and in lactating mothers. MYLOTARG may cause fetal harm
when administered to a pregnant woman. The reported rate of Grade 3
or 4 thrombocytopenia, neutropenia, anemia, and bleeding were 99%,
98%, 52%, and 13%, respectively. Thirty percent of patients
experienced severe infections, including sepsis (17%) and pneumonia
The most common adverse events (greater than or equal to 20%) were
fever (82%), nausea (68%), chills (66%), vomiting (58%),
thrombocytopenia (50%), leukopenia (47%), headache (37%), asthenia
(36%), abdominal pain (32%), diarrhea (32%), epistaxis (28%), dyspnea
(26%), hypokalemia (26%), sepsis (26%), anorexia (25%), stomatitis
(25%), liver function tests abnormal (24%), constipation (23%),
anemia (22%), local reaction (22%), herpes simplex (21%), and
MYLOTARG can produce a postinfusion symptom complex of fever and
chills, and less commonly hypotension and dyspnea during the first 24
hours after administration. Patients should receive diphenhydramine
50 mg po and acetaminophen 650-1000 mg po 1 hour before MYLOTARG
administration. Two additional doses of acetaminophen 650-1000 mg po
every 4 hours may be given. Fever and chills were commonly reported
despite premedication with diphenhydramine and acetaminophen. Vital
signs should be monitored during infusion and for 4 hours following
infusion. Methylprednisolone given prior to MYLOTARG(R) (gemtuzumab
ozogamicin) infusion may ameliorate infusion-related symptoms.
Severe myelosuppression will occur in all patients given the
recommended dose of this agent. Careful hematologic monitoring is
required. Systemic infections should be treated.
Please see MYLOTARG full U.S. prescribing information at
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
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 pharmaceutical, vaccines,
biotechnology products 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 based on current expectations of
future events and 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 the
inherent uncertainty of the timing and success of, and expense
associated with, research, development, regulatory approval and
commercialization of our products, including with respect to our
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; data generated on our 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." 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.
Web site: http://www.wyeth.com
ots Originaltext: Wyeth Pharmaceuticals
Im Internet recherchierbar: http://www.presseportal.ch
Media, Natalie de Vane of Wyeth Pharmaceuticals, +1-484-865-5139, or
Douglas Petkus of Wyeth, +1-973-660-5218; Investors, Justin Victoria
of Wyeth, +1-973-660-5340