Basel, 23 April 2010
Genentech submits supplemental application to FDA for Herceptin in advanced HER2-positive stomach cancer
Application Based on Positive Results from International Phase III Study
Genentech, Inc., a wholly owned member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the company has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for Herceptin (trastuzumab) plus chemotherapy in people with advanced, HER2-positive adenocarcinoma of the stomach, including gastroesophageal junction cancer. The application is based on positive results from a Phase III study, known as ToGA, which showed that people receiving Herceptin plus chemotherapy lived longer compared to people who received chemotherapy alone.
“This application reflects our commitment to developing more personalized medicines for people with cancer. By using diagnostics to identify the right patients for our medicines, it is our hope that Herceptin used with chemotherapy will become the first targeted option for advanced HER2-positive stomach cancer,” said Hal Barron, M.D., executive vice president Global Development and chief medical officer. “We look forward to working with the FDA and the diagnostic company on this application.”
About the ToGA study
The international Phase III study enrolled 594 people with locally advanced or metastatic HER2-positive stomach cancer who were randomized to receive Herceptin plus chemotherapy (Xeloda [ capecitabine tablets] or intravenous 5-flourouracil and cisplatin) or chemotherapy alone. Overall survival (OS), the primary endpoint, was significantly improved in people who received Herceptin plus chemotherapy compared to those who received chemotherapy alone (HR=0.74, p=0.0046, median OS 13.8 vs. 11.1 months). No new or unexpected adverse events were seen in the Herceptin patient group, and no statistically significant difference in symptomatic congestive heart failure was seen between the two groups (one person in the Herceptin group and two people in the comparison group experienced heart failure). All people in this trial were tested for their HER2 status using diagnostics developed by Dako.
In 2009, the American Society of Clinical Oncology (ASCO) named the results of ToGA as one of the major cancer research advances of the year.
About Herceptin in stomach cancer outside the US
In January 2010, the European Commission approved Herceptin in combination with capecitabine or intravenous 5-fluorouracil and cisplatin for the treatment of patients with HER2-positive metastatic adenocarcinoma of the stomach or gastro-esophageal junction who have not received prior anti-cancer treatment for their metastatic disease. The approval was based on the results of the ToGA trial which showed that overall survival for patients with particularly high levels of HER2 was 16 months when treated with Herceptin versus 11.8 months (on average) for patients receiving chemotherapy alone. The EU label recommends Herceptin for patients expressing particularly high levels of HER2.
Herceptin has also been approved for use in HER2-positive stomach cancer in South Korea (combination with capecitabine or 5-fluorouracil and a platinum agent for the treatment of patients with HER2-positive metastatic adenocarcinoma of the stomach or gastro-esophageal junction who have not received prior anti-cancer treatment for their metastatic disease). Filing for approval took place in Russia, Turkey, Brazil, Mexico, India, Japan and Taiwan. Further filings will be made in the rest of the world.
Accurate and rapid HER2 testing is crucial to ensure appropriate treatment for advanced/metastatic stomach cancer. In the ToGA trial, Dako’s HER2 test (HercepTest) was used to identify HER2-positivity in stomach cancer patients. Roche also collaborates with Ventana, who provide validated assays for gastric cancer which will be used to test for HER2 status in stomach cancer. These validated assays used to detect HER2-positivity in breast and gastric cancer are the same, however, the interpretation of the results in gastric is different.
Herceptin is a humanised antibody, designed to target and block the function of HER2, a protein produced by a specific gene with cancer-causing potential. The mode of action of Herceptin is unique in that it activates the body’s immune system and suppresses HER2 to target and destroy the tumour. Herceptin has demonstrated unprecedented efficacy in treating both early and advanced (metastatic) HER2-positive breast cancer. Given on its own as monotherapy as well as in combination with or following standard chemotherapy, Herceptin has been shown to improve response rates, disease-free survival and overall survival while maintaining quality of life in women with HER2-positive breast cancer.
Herceptin is marketed in the United States by Genentech, in Japan by Chugai and internationally by Roche. Since 1998, Herceptin has been used to treat more than 740,000 patients with HER2-positive breast cancer worldwide.
Important Safety Information
Herceptin treatment can result in heart problems, including those without symptoms (reduced heart function) and those with symptoms (congestive heart failure). Some patients have had serious infusion reactions and lung problems; fatal infusion reactions have been reported. Worsening of low white blood cell counts associated with chemotherapy has also occurred. Herceptin can cause low amniotic fluid levels and harm to the fetus when taken by a pregnant woman. The most common side effects associated with Herceptin were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, shortness of breath, rash, low white and red blood cells, and muscle pain. Because everyone is different, it is not possible to predict what side effects any one person will have. Patients with questions or concerns about side effects should talk to their doctor.
Xeloda (capecitabine) is a highly effective targeted oral chemotherapy offering patients a survival advantage when taken on its own or in combination with other anticancer drugs. Xeloda uniquely activates the cancer-killing agent 5-FU (5-fluorouracil) directly inside the cancer cells. Xeloda tablets can be taken by patients in their own home, reducing the number of hospital or clinic visits.
Licensed and marketed by Roche in more than 100 countries worldwide, Xeloda has over 11 years proven clinical experience providing an effective and flexible treatment option to over 1.8 million people with cancer. Xeloda is currently approved in:
Metastatic Colorectal Cancer
- Monotherapy first-line (US , EU and ROW) - 2001
- In combination with any chemotherapy in all lines of treatment with or without Avastin (EU/RoW) - 2008
- In combination with oxaliplatin for the treatment of patients with advanced or refractory colorectal cancer who are not candidates for curative surgery (Japan) - 2009
Adjuvant Colon Cancer
- Monotherapy (US & EU) – 2005
- Monotherapy (Japan) - 2007
Advanced Gastric Cancer
- First-line treatment (South Korea) - 2002
- In combination with platinum-based chemotherapy first-line (EU and ROW) - 2007
Metastatic Breast Cancer
- Monotherapy first-line in patients with tumours resistant to taxanes and anthracyclines - (US) 1998 and (EU) 2002
- In combination with docetaxel in patients whose disease has progressed following iv chemotherapy with anthracyclines - (US) 2001 and (EU) 2002
- In patients with inoperable or recurrent breast cancer - (Japan) 2003
Xeloda Boxed WARNINGS and Additional Important Safety Information
Xeloda may increase the effect of blood thinning medicines, such as warfarin and other coumarin derivatives, and could lead to serious side effects if taken at the same time as these medicines. It is very important that doctors closely monitor patients who are taking blood thinning medicines and Xeloda, checking more often how quickly their patients' blood clots and, if needed, changing the dose of the blood thinning medicine.
The most common side effects of Xeloda are: diarrhea, nausea, vomiting, sores in the mouth and throat (stomatitis), stomach area (abdominal) pain, upset stomach, constipation, loss of appetite, and too much water loss from the body (dehydration). These side effects are more common in patients age 80 and older. Other common side effects are hand-and-foot syndrome (tingling, numbness, pain, swelling or redness in the palms of the hands or soles of the feet); rash; dry, itchy or discolored skin; nail problems; hair loss; tiredness; weakness; dizziness; headache; fever; pain (including chest, back, joint and muscle pain); trouble sleeping; and taste problems. Patients should tell their doctor if they have heart problems because they could have more side effects related to their heart.
These side effects may differ when taking Xeloda with docetaxel. Patients should consult their doctor for possible side effects that may be caused by taking Xeloda with other therapies.
Women should not become pregnant while taking Xeloda and should not take Xeloda while nursing a baby.
For full Prescribing Information, including Boxed WARNINGS and important safety information on Xeloda please visit http://www.xeloda.com.
About Stomach Cancer
According to the American Cancer Society (ACS), an estimated 21,130 Americans were diagnosed with stomach cancer and more than 10,600 Americans died from the disease in 2009. More than 64,000 Americans are currently living with the disease. Early diagnosis is challenging because many people do not have symptoms until the disease has advanced into late stages when the tumor cannot be surgically removed or has spread to other parts of the body.
Cancer of the stomach or the area where the stomach and esophagus join (gastroesophageal junction) can be further divided into categories based on the genetics of the tumor, such as human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative (sometimes referred to as “HER2-normal”). In ToGA, about 22 percent of stomach cancers were HER2-positive.
Worldwide, stomach cancer is the second most common cause of cancer related death in the world and is the fourth most commonly diagnosed cancer, with over 1,000,000 cases of stomach cancer diagnosed each year. Advanced stomach cancer is associated with a poor prognosis; the median survival time after diagnosis is approximately 10-11 months with currently available therapies. Approximately 15-18% of stomach tumours show high levels of HER2. , Early diagnosis of this disease is challenging because most patients do not show symptoms in the early stage.
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2009, Roche had over 80,000 employees worldwide and invested almost 10 billion Swiss francs in R&D. The Group posted sales of 49.1 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines for patients with serious or life-threatening medical conditions. The company, a wholly owned member of the Roche Groups, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com
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