Saturday, Jun 2, 2007
Chicago -- June 2, 2007 --Genentech, Inc. (NYSE: DNA) today announced that a Roche-sponsored, randomized placebo-controlled Phase III clinical study of Avastin®(bevacizumab) in combination with interferon alfa-2a therapy increased the median time patients with first-line metastatic renal cell carcinoma (mRCC) lived without their cancer growing or spreading as defined by progression-free survival (PFS). Patients receiving Avastin plus interferon alfa-2a therapy experienced a 59 percent improvement in PFS (based on a hazard ratio of 0.63) compared to those receiving interferon alfa-2a therapy alone.
The American Society of Clinical Oncology (ASCO) today featured the results of the trial, known as AVOREN, in a press briefing at its 43rd Annual Meeting in Chicago. These data were also highlighted in a plenary session by Bernard Escudier, M.D., head of the immunotherapy and innovative therapy unit at the Gustave-Roussy Institute, Paris, France (Abstract #3 — Monday, June 4, 2:30 p.m. CDT).
"Patients with metastatic renal cell carcinoma often express elevated levels of vascular endothelial growth factor, or VEGF,"said Dr. Escudier. "These data suggest that specifically blocking VEGF with Avastin may provide important clinical benefit for patients with this difficult-to-treat disease."
"These Phase III results were significant because kidney cancer remains a disease where new and better treatments are needed,"said Hal Barron, M.D., Genentech's senior vice president, Development and chief medical officer. "This is the fourth kind of cancer in which Avastin has demonstrated positive results in a Phase III study, reinforcing our belief in the potential of specifically targeting VEGF in a broad spectrum of solid tumor types."
The 59 percent improvement in PFS can also be referred to as a 37 percent reduction in the risk of cancer progression or death, as calculated by the hazard ratio (HR) of 0.63. Patients who received Avastin plus interferon had a median PFS of 10.2 months compared to 5.4 months for patients who received interferon alone (p less than 0.0001). The tumor response rate was 31 percent (95/306) in the Avastin plus interferon arm, compared to 13 percent (37/289) in the patients who received interferon alone.
Adverse events in this study appeared to be similar to those previously reported for interferon and for Avastin. The most common adverse events that occurred more often in the Avastin plus interferon arm included bleeding, hypertension and proteinuria. Severe (Grade 3 or greater) fatigue occurred in 23 percent in the Avastin arm compared to 15 percent in the interferon alone arm. Other Grade 3 or greater events that occurred more often in the Avastin plus interferon arm included proteinuria (22 percent vs. 0 percent), hypertension (4 percent vs. 1 percent), hemorrhage (3 percent vs. 0 percent), venous thromboembolism (2 percent vs. 1 percent), gastrointestinal perforations (2 percent vs. 0 percent) and arterial ischemia (1 percent vs. 0 percent).
About the Trial Design
The study, which included 649 patients worldwide, was originally designed to measure an improvement in overall survival. However, in prior consultation with the U.S. Food and Drug Administration and European regulatory authorities, the primary analysis endpoint was revised to assess improvement in PFS, defined as the length of time the tumor did not grow or patient death did not occur. Secondary endpoints of the study included overall survival, time to progression, time to treatment failure, overall response rate and safety profile. The study protocol specified an interim overall survival analysis be performed at approximately 50 percent of events. That interim analysis showed a trend toward an increase in overall survival. However, the final survival data are not yet mature and will be submitted for presentation at a future medical meeting.
Another Phase III study of Avastin in combination with interferon in first-line mRCC is being conducted in the U.S. by the Cancer and Leukemia Group B, a national clinical research group sponsored by the National Cancer Institute. The results of this trial have not yet been reported. In addition, Genentech is planning a randomized study of Avastin in combination with other targeted agents in mRCC.
Renal cell carcinoma is the most common type of kidney cancer, accounting for nine out of 10 cases, and fewer than 10 percent of late-stage kidney cancer patients live five years following diagnosis. According to the American Cancer Society, there will be 51,190 new cases of kidney cancer and 12,890 kidney cancer deaths in 2007 in the U.S.
Avastin is a therapeutic antibody designed to specifically inhibit vascular endothelial growth factor (VEGF), a protein that plays an important role in angiogenesis and the maintenance of existing blood vessels throughout the lifecycle of a tumor. By inhibiting VEGF, Avastin is designed to interfere with the blood supply to a tumor, which is thought to be critical to a tumor's ability to grow and spread in the body (metastasize). For more information on angiogenesis, visit http://www.gene.com. For full prescribing information and Boxed Warnings on Avastin, visit http://www.avastin.com.
The FDA approved Avastin on February 26, 2004, as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy. Avastin is also indicated in combination with intravenous 5-FU-based chemotherapy for second-line treatment of patients with metastatic carcinoma of the colon or rectum. On October 11, 2006, the FDA approved Avastin in combination with carboplatin and paclitaxel for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer.
Avastin has a well-characterized safety profile in its approved indications with more than 200,000 patients treated to date. The most serious adverse events associated with Avastin across all trials were gastrointestinal perforation, wound healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome (RPLS), neutropenia and infection, nephrotic syndrome and congestive heart failure. The most common adverse events in patients receiving Avastin were asthenia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermatitis and proteinuria.
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. A considerable number of the currently approved biotechnology products originated from or are based on Genentech science. Genentech manufactures and commercializes multiple biotechnology products and licenses several additional products to other companies. The company has headquarters in South San Francisco, Calif., and is listed on the New York Stock Exchange under the symbol DNA. For additional information about the company, please visit http://www.gene.com.
This press release contains forward-looking statements regarding the potential of Avastin. Such statements are predictions and involve risks and uncertainties such that actual results may differ materially. Among other things, the potential of Avastin may be affected by a number of factors, including unexpected safety, efficacy or manufacturing issues, additional time requirements for data analysis, BLA preparation and decision making, FDA actions or delays, failure to obtain or maintain FDA approval, competition, pricing, reimbursement, the ability to supply product, product withdrawals and new product approvals and launches, intellectual property or contract rights, or higher than anticipated costs of sales or other expenses. Please also refer to Genentech's periodic reports filed with the Securities and Exchange Commission. Genentech disclaims, and does not undertake any obligation to, update or revise any forward-looking statements in this press release.