Pfizer announced today that the Committee for Human Medicinal Products (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion regarding the marketing authorization of axitinib in the European Union (EU), for the treatment of adult patients with advanced renal cell carcinoma (RCC), a type of advanced kidney cancer, after failure of prior treatment with sunitinib or a cytokine.
Axitinib, a kinase inhibitor, is an oral therapy that was designed to selectively inhibit tyrosine kinases, including vascular endothelial growth factor (VEGF) receptors 1, 2 and 3, which are receptors that can influence tumor growth, vascular angiogenesis, and progression of cancer.1
The CHMP's positive opinion will be reviewed by the European Commission, which has the authority to approve medicines for the EU. Pfizer anticipates a decision from the Commission in the coming months.
"Pfizer is very pleased that the CHMP has adopted a positive opinion for axitinib as a second-line treatment for advanced renal cell carcinoma, and we look forward to the decision of the European Commission," said Mace Rothenberg, MD, senior vice president of clinical development and medical affairs for Pfizer's Oncology Business Unit. "Despite recent advances in the treatment of advanced kidney cancer, there is a clear need for additional treatment options for patients whose disease has progressed following first-line medications."
Axitinib is an investigational agent, and has not been approved in the European Union. In January, axitinib was approved by the U.S. Food and Drug Administration (FDA) as INLYTA®. Following is the U.S. safety information.
Important INLYTA® (axitinib) U.S. Safety Information
Hypertension including hypertensive crisis has been observed. Blood pressure should be well controlled prior to initiating INLYTA. Monitor for hypertension and treat as needed. For persistent hypertension, despite use of antihypertensive medications, reduce the dose. Discontinue INLYTA if hypertension is severe and persistent despite use of antihypertensive therapy and dose reduction of INLYTA, and discontinuation should be considered if there is evidence of hypertensive crisis.
Arterial and venous thrombotic events have been observed and can be fatal. Use with caution in patients who are at increased risk or who have a history of these events.
Hemorrhagic events, including fatal events, have been reported. INLYTA has not been studied in patients with evidence of untreated brain metastasis or recent active gastrointestinal bleeding and should not be used in those patients. If any bleeding requires medical intervention, temporarily interrupt the INLYTA dose.
Gastrointestinal perforation and fistula, including death, have occurred. Use with caution in patients at risk for gastrointestinal perforation or fistula. Monitor for symptoms of gastrointestinal perforation or fistula periodically throughout treatment.
Hypothyroidism requiring thyroid hormone replacement has been reported. Monitor thyroid function before initiation of, and periodically throughout, treatment.
Stop INLYTA at least 24 hours prior to scheduled surgery.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has been observed. If signs or symptoms occur, permanently discontinue treatment.
Monitor for proteinuria before initiation of, and periodically throughout, treatment. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment.
Liver enzyme elevation has been observed during treatment with INLYTA. Monitor ALT, AST, and bilirubin before initiation of, and periodically throughout, treatment.
For patients with moderate hepatic impairment, the starting dose should be decreased. INLYTA has not been studied in patients with severe hepatic impairment.
Women of childbearing potential should be advised of potential hazard to the fetus and to avoid becoming pregnant while receiving INLYTA. Avoid strong CYP3A4/5 inhibitors. If unavoidable, reduce the dose. Grapefruit or grapefruit juice may also increase INLYTA plasma concentrations and should be avoided.
Avoid strong CYP3A4/5 inducers and, if possible, avoid moderate CYP3A4/5 inducers.
The most common (=20%) adverse events (AEs) occurring in patients receiving INLYTA (all grades, vs sorafenib) were diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome, weight decreased, vomiting, asthenia, and constipation.
The most common (=10%) grade 3/4 AEs occurring in patients receiving INLYTA (vs sorafenib) were hypertension, diarrhea, and fatigue.
The most common (=20%) lab abnormalities occurring in patients receiving INLYTA (all grades, vs sorafenib) included increased creatinine, decreased bicarbonate, hypocalcemia, decreased hemoglobin, decreased lymphocytes (absolute), increased ALP, hyperglycemia, increased lipase, increased amylase, increased ALT and increased AST.
About SUTENT® (sunitinib malate)
SUTENT is approved for gastrointestinal stromal tumors (GIST) after disease progression on or intolerance to imatinib mesylate, for advanced RCC, and for progressive, well-differentiated pancreatic neuroendocrine tumors (NET) in patients with unresectable locally advanced or metastatic disease.
SUTENT is an oral multi-kinase inhibitor that works by blocking multiple molecular targets implicated in the growth, proliferation and spread of cancer. Two important SUTENT targets, vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) are expressed by many types of solid tumors and are thought to play a crucial role in angiogenesis, the process by which tumors acquire blood vessels, oxygen and nutrients needed for growth. SUTENT also inhibits other targets important to tumor growth, including KIT, FLT3 and RET.
Important SUTENT® (sunitinib malate) Safety Information
Hepatotoxicity has been observed in clinical trials and post-marketing experience. This hepatotoxicity may be severe, and deaths have been reported. Monitor liver function tests before initiation of treatment, during each cycle of treatment, and as clinically indicated. SUTENT should be interrupted for Grade 3 or 4 drug-related hepatic adverse events and discontinued if there is no resolution. Do not restart SUTENT if patients subsequently experience severe changes in liver function tests or have other signs and symptoms of liver failure. Women of childbearing potential should be advised of the potential hazard to the fetus and to avoid becoming pregnant.
Given the potential for serious adverse reactions (ARs) in nursing infants, a decision should be made whether to discontinue nursing or SUTENT.
Cardiovascular events, including heart failure, myocardial disorders, and cardiomyopathy, some of which were fatal, have been reported. Monitor patients for signs and symptoms of congestive heart failure (CHF) and, in the presence of clinical manifestations, discontinuation is recommended. Patients who presented with cardiac events, pulmonary embolism, or cerebrovascular events within the previous 12 months were excluded from clinical studies.
SUTENT has been shown to prolong QT interval in a dose-dependent manner, which may lead to an increased risk for ventricular arrhythmias including torsades de pointes, which has been seen in <0.1% of patients. Monitoring with on-treatment electrocardiograms and electrolytes should be considered.
Hypertension may occur. Monitor blood pressure and treat as needed with standard antihypertensive therapy. In cases of severe hypertension, temporary suspension of SUTENT is recommended until hypertension is controlled.
There have been rare (<1%) nonfatal reports of subjects presenting with seizures and radiological evidence of reversible posterior leukoencephalopathy syndrome (RPLS).
Hemorrhagic events, including tumor-related hemorrhage such as pulmonary hemorrhage, have occurred. Some of these events were fatal. Perform serial complete blood counts (CBCs) and physical examinations. Osteonecrosis of the jaw (ONJ) has been reported. Consider preventive dentistry prior to treatment with SUTENT. If possible, avoid invasive dental procedures, particularly in patients receiving bisphosphonates. Cases of tumor lysis syndrome (TLS) have been reported primarily in patients with high tumor burden. Monitor these patients closely and treat as clinically indicated.
Thyroid dysfunction may occur. Monitor thyroid function in patients with signs and/or symptoms of hypothyroidism or hyperthyroidism and treat per standard medical practice.
Cases of impaired wound healing have been reported. Temporary interruption of therapy with SUTENT is recommended in patients undergoing major surgical procedures.
Adrenal hemorrhage was observed in animal studies. Monitor adrenal function in case of stress such as surgery, trauma, or severe infection.
CBCs with platelet count and serum chemistries including phosphate should be performed at the beginning of each treatment cycle for patients receiving treatment with SUTENT.
Dose adjustments are recommended when administered with CYP3A4 inhibitors or inducers.
The most common ARs occurring in =20% of patients receiving SUTENT for treatment-naïve metastatic RCC (all grades, vs IFNa) were diarrhea, fatigue, nausea, anorexia, altered taste, mucositis/stomatitis, pain in extremity/limb discomfort, vomiting, bleeding, all sites, hypertension, dyspepsia, arthralgia, abdominal pain, rash, hand-foot syndrome, back pain, cough, asthenia, dyspnea, skin discoloration/yellow skin, peripheral edema, headache, constipation, dry skin, fever, and hair color changes. The most common grade 3/4 ARs (occurring in =5% of patients with RCC receiving SUTENT vs IFNa) were fatigue, hypertension, asthenia, diarrhea, hand-foot syndrome, dyspnea, nausea, back pain, pain in extremity/limb discomfort, vomiting, and abdominal pain.
The most common grade 3/4 lab abnormalities (occurring in =5% of patients with RCC receiving SUTENT vs IFNa) included lymphocytes, lipase, neutrophils, uric acid, platelets, hemoglobin, sodium decreased, leukocytes, glucose increased, phosphorus, and amylase. For more information on INLYTA (axitinib) and SUTENT (sunitinib malate), including full prescribing information, please visit www.pfizer.com.
About Pfizer Oncology
Pfizer Oncology is committed to the discovery, investigation and development of innovative treatment options to improve the outlook for cancer patients worldwide. Our strong pipeline of biologics and small molecules, one of the most robust in the industry, is studied with precise focus on identifying and translating the best scientific breakthroughs into clinical application for patients across a wide range of cancers. By working collaboratively with academic institutions, individual researchers, cooperative research groups, governments, and licensing partners, Pfizer Oncology strives to cure or control cancer with breakthrough medicines, to deliver the right drug for each patient at the right time.
As a leader in the treatment of advanced RCC, Pfizer Oncology is dedicated to offering multiple treatments and investigating new agents in different populations and stages of disease. Pfizer Oncology has helped transform treatment expectations for advanced kidney cancer, providing confidence and options to physicians, allowing them to better tailor treatment for different patient populations.
For more information please visit www.pfizer.com
The information contained in this release is as of May 25, 2012. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information that involves substantial risks and uncertainties about a product candidate, axitinib, including its potential benefits, that is under review by the European Commission. Such risks and uncertainties include, among other things, the uncertainties inherent in research and development; whether and when the European Commission and regulatory authorities in other jurisdictions in which applications have been or may be filed will approveapplications for axitinib as well as their decisions regarding labeling and other matters that could affect its availability or commercial potential; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer's Annual Report on Form 10-K for the fiscal year ended December 31, 2011 and in its reports on Form 10-Q and Form 8-K.
1 Axitinib Summary of Product Characteristics.
Jenifer Antonacci, +1-610-427-0369
Jennifer Davis, +1-212-733-0717