Wednesday, Oct 11, 2006
South San Francisco, Calif. -- October 11, 2006 --Genentech, Inc. (NYSE: DNA) announced today that the U.S. Food and Drug Administration (FDA) has approved Avastin® (bevacizumab) to be used in combination with carboplatin and paclitaxel chemotherapy for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer (NSCLC), the most common type of lung cancer. The approval is based on a Phase III study (E4599) that showed Avastin in combination with chemotherapy resulted in a 25 percent improvement in overall survival compared to chemotherapy alone (based on a hazard ratio of 0.80).
"Bevacizumab, in combination with chemotherapy, is the first therapy in 10 years to improve on standard first-line treatment for advanced lung cancer and the first FDA-approved therapy ever to extend survival for these patients beyond one year in a large, randomized clinical study," said Alan Sandler, M.D., director of Medical Thoracic Oncology at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., and lead investigator on the E4599 trial. "With this survival benefit, bevacizumab represents an important therapy for many advanced lung cancer patients fighting this difficult disease."
"Lung cancer is responsible for more than one-third of all U.S. cancer deaths, killing more people than breast, prostate, colon, liver and kidney cancers combined," said Laurie Fenton, president of the Lung Cancer Alliance in Washington, D.C. "The approval of Avastin plus chemotherapy is a significant stride in the right direction, and we are pleased that Genentech continues to make lung cancer a priority."
The FDA approval for this new indication was based on results from E4599, a randomized, controlled, multi-center trial that enrolled 878 patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC. Patients with mixed histology were excluded if the predominant cell type was squamous. Results showed that patients receiving Avastin plus paclitaxel and carboplatin chemotherapy had a 25 percent improvement in overall survival, the trial's primary endpoint, compared to patients who received paclitaxel and carboplatin alone (based on a hazard ratio of 0.80). One-year survival was 51 percent in the Avastin plus chemotherapy arm versus 44 percent in the chemotherapy-alone arm. Median survival of patients treated with Avastin plus chemotherapy was 12.3 months, compared to 10.3 months for patients treated with chemotherapy alone.
The E4599 trial was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, under a Cooperative Research and Development Agreement between NCI and Genentech. The trial was conducted by a network of researchers led by the Eastern Cooperative Oncology Group (ECOG).
E4599 Safety Analysis
The most common Grade 3-5 (severe) adverse events in Study E4599 seen in Avastin-treated patients were neutropenia (low white blood cell count), fatigue, hypertension (high blood pressure), infection and hemorrhage.
In Study E4599, the rate of pulmonary hemorrhage requiring medical intervention for the paclitaxel and carboplatin plus Avastin arm was 2.3 percent (10/427), compared to 0.5 percent (2/441) for the paclitaxel and carboplatin-alone arm. There were seven deaths due to pulmonary hemorrhage reported by investigators in the paclitaxel and carboplatin-plus Avastin arm, as compared to one in the paclitaxel and carboplatin-alone arm.
In previous clinical experience with Avastin in combination with paclitaxel and carboplatin in NSCLC, patients with a specific type of NSCLC called squamous cell carcinoma had a higher risk of experiencing life-threatening or fatal pulmonary bleeding. Squamous cells are a particular kind of cell that form in the lining of the air ducts in the lung. Because of the risk of bleeding attributed to this population, patients with NSCLC classified as predominantly squamous histology were not included in the E4599 trial.
About the New Avastin Annual Expenditure Cap and Genentech's Access to Care Programs
Genentech also announced today that the company plans to initiate a first-of-its-kind program to cap the overall expense of Avastin to $55,000 per year per eligible patient for any FDA-approved indication. The program will be available for eligible patients regardless of whether they are insured. The company plans to launch the new program in January 2007. In addition, the company announced that it has doubled its contribution to independent charities that provide co-pay assistance to a total of $50 million.
"The clinical development program that led to Avastin's three FDA approvals suggested dose and duration vary depending on tumor type," said Arthur D. Levinson, Ph.D., Genentech's chairman and chief executive officer. "The new expenditure cap on Avastin is a step Genentech is taking to address this variability in current and future FDA-approved indications. This new program, along with the increased contribution to independent charities that provide co-pay assistance to patients, continues our 20-year history of commitment to patient access."
The price of Avastin was established in February 2004 upon the FDA approval of the drug for the treatment of first-line colorectal cancer in combination with 5-FU based chemotherapy. At that time, the monthly price of Avastin was set below the standard of care chemotherapy for metastatic colorectal cancer at approximately $4,400.
In advanced lung cancer, a higher dose of Avastin is indicated. This dose was based on clinical data from a randomized dose-ranging Phase II study of Avastin in combination with chemotherapy. Based on this trial, ECOG and NCI selected the higher dose for the pivotal Phase III trial in NSCLC. The typical monthly cost of Avastin at this dose is approximately $8,800 and, based on median progression-free survival as measured in the E4599 trial, the average cost per course of therapy in NSCLC is approximately $56,000.
Avastin is covered by most insurers and Medicare for its approved indications. Genentech's donation to independent co-pay charities helps provide assistance to eligible patients with higher co-pay burdens. For eligible uninsured patients, the Genentech Access to Care Foundation (GATCF) provides Avastin for free.
Genentech has provided more than $850 million in free drug to patients since 1990. In 2005 alone, GATCF supported over 18,000 patients by providing approximately $200 million of free product. To learn more about the GATCF, independent charities that provide co-pay assistance to patients and potential financial assistance options, patients can speak with an Alternative Funding Specialist from Genentech's Single Point of Contact (SPOC) group by calling 888-249-4918 or visiting http://www.SPOConline.com.
About Lung Cancer
According to the American Cancer Society, lung cancer is the single largest cause of cancer deaths among men and women in the U.S. and is responsible for nearly 30 percent of cancer deaths in this country. The American Cancer Society estimates that more than 170,000 Americans will be diagnosed with lung cancer this year, and 162,000 Americans will die of the disease this year. NSCLC is the most common type of lung cancer.
Avastin, in combination with intravenous 5-fluorouracil (FU)-based chemotherapy, is indicated for first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum; and 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 (NSCLC). For full prescribing information and boxed warnings on Avastin and information about angiogenesis, visit http://www.gene.com. For more information on Avastin, visit http://www.avastin.com.
The FDA first approved Avastin on February 26, 2004, as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy. The National Comprehensive Cancer Network recommends Avastin plus chemotherapy as a standard treatment for the first- and second-line treatment of metastatic colorectal cancer and as a first-line treatment of advanced non-squamous NSCLC.
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.
About the Avastin Development Program
Based on data showing that VEGF may play a broad role in a range of cancers, Genentech is pursuing a broad development program for Avastin that currently includes 130 clinical trials across 25 different types of cancer. Avastin is being evaluated in Phase III clinical trials for its potential use in adjuvant and metastatic colorectal, renal cell (kidney), breast, non-small cell lung, prostate and ovarian cancers. Avastin is also being evaluated in earlier stage trials as a potential therapy in a variety of solid tumor cancers and hematologic malignancies. For further information about Avastin clinical trials, please call 888-662-6728.
About VEGF and Tumor Angiogenesis
Genentech is a leader in research and product development in the area of angiogenesis, the process by which new blood vessels are formed. The link between angiogenesis and cancer growth has been discussed by many researchers for decades; however it was not until 1989 that a key growth factor influencing the process, vascular endothelial growth factor (VEGF), was discovered by Napoleone Ferrara, M.D., a staff scientist at Genentech. Ferrara and his team at Genentech cloned VEGF, providing some of the first evidence that a specific angiogenic growth factor existed. This research was published in the journal Science in 1989. Ferrara then created a mouse antibody to this protein.
In 1993, in a study published in the journal Nature, Ferrara and his team demonstrated that the antibody directed against VEGF could suppress angiogenesis and tumor growth in preclinical models, providing compelling evidence that VEGF can play an important role in tumor growth. Clinical studies with a humanized version of the antibody, Avastin, began in 1997.
About Genentech BioOncology
Genentech is committed to changing the way cancer is treated by establishing a broad oncology portfolio of innovative, targeted therapies with the goal of improving patients' lives. The company is the leading provider of anti-tumor therapeutics in the United States. Genentech is conducting clinical development programs for Rituxan® (Rituximab), Herceptin® (Trastuzumab), Avastin® (bevacizumab), and Tarceva® (erlotinib), and markets all four products in the United States, either alone (Avastin and Herceptin) or with Biogen Idec Inc. (Rituxan) or OSI Pharmaceuticals, Inc. (Tarceva).
The company has a robust pipeline of potential oncology therapies with a focus on four key areas: angiogenesis, apoptosis (i.e., programmed cell death), the HER pathway, and B-cell biology. An investigational antibody directed at the HER pathway is currently in Phase II trials. In early development are a small molecule directed at the hedgehog pathway and an investigational agent targeting apoptosis.
Founded 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.
For the full prescribing information for Tarceva and the full prescribing information and Boxed Warnings for Rituxan, Herceptin, and Avastin, please visit http://www.gene.com.
This press release contains forward-looking statements regarding the timeframe for launching the Avastin Annual Expenditure Cap Program and Avastin as a potential therapy for cancer. Such statements are predictions and involve risks and uncertainties such that actual results may differ materially. Among other things, the timeframe for launch of the Avastin program could be affected by the regulatory, reimbursement and pricing environment; and Avastin's potential as a cancer therapy could be affected by the foregoing and by unexpected safety, efficacy or manufacturing issues, additional time requirements for data analysis, BLA preparation or decision-making, need for additional clinical studies, FDA actions or delays, failure to obtain or maintain FDA approval, competition, intellectual property or contract rights, the ability to supply product, or product withdrawal. 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 the forward-looking statements in this press release.