Sunday, Apr 20, 2008
South San Francisco, Calif. -- April 20, 2008 --Genentech, Inc. (NYSE: DNA) today announced an update for the previously reported Roche-sponsored international Phase III clinical study (AVAiL) of Avastin® (bevacizumab) in combination with gemcitabine and cisplatin chemotherapy, in patients with advanced, non-squamous, non-small cell lung cancer (NSCLC). The update confirmed the clinically and statistically significant improvement in the primary endpoint of progression free survival (PFS) for the two different doses of Avastin studied in the trial (15 mg/kg and 7.5 mg/kg) compared to chemotherapy alone. The study did not demonstrate a statistically significant prolongation of overall survival, a secondary endpoint, for either dose in combination with gemcitabine and cisplatin chemotherapy compared to chemotherapy alone. Median survival of patients in all arms of the study exceeded one year, longer than previously reported survival times in this indication.
Importantly, the Genentech pivotal Phase III U.S. study (E4599) of Avastin plus carboplatin and paclitaxel chemotherapy showed a statistically significant improvement in overall survival for patients with advanced lung cancer compared to chemotherapy alone (25 percent improvement, hazard ratio 0.80).
In 2006, the Food and Drug Administration (FDA) approved Avastin for the first-line treatment of unresectable, locally advanced, recurrent metastatic, non-squamous, NSCLC on the basis of E4599. The study had a primary endpoint of overall survival and tested 15 mg/kg of Avastin with a different chemotherapy regimen (carboplatin and paclitaxel) than the AVAiL study.
"The statistically significant improvement in overall survival observed in E4599, as well as the safety and improvement in progression-free survival in AVAiL and E4599, give us confidence in Avastin's safety and efficacy for patients with advanced, non-squamous, non-small cell lung cancer. These studies reinforce our belief that Avastin is an important treatment option for patients with this most common form of lung cancer," said Hal Barron, M.D., senior vice president, Development and chief medical officer.
No new safety signals for Avastin were observed in the study, and there were no clinically meaningful differences in safety between the two doses of Avastin.
AVAiL is an international study, conducted outside of the U.S., that enrolled 1,043 patients with previously untreated, advanced, non-squamous, NSCLC. The study met its primary endpoint of progression-free survival, defined as the time from randomization to the first event of progression or death, and was presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in 2007. Secondary endpoints included overall survival, response rate, time to treatment failure and safety. Patients were randomized to receive cisplatin (80 mg/m2 on Day 1) and gemcitabine (1,250 mg/m2 on Day 1 and Day 8) chemotherapy every three weeks for up to six cycles plus either Avastin 15 mg/kg or Avastin 7.5 mg/kg every three weeks (until disease progression), or placebo. Physicians and patients in the study were blinded to treatment with Avastin but not dose.
E4599 was 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. 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).
Avastin is a therapeutic antibody designed to specifically inhibit the vascular endothelial growth factor (VEGF) protein, a potent source of angiogenesis. Angiogenesis is a process that connects tumors to the blood supply. 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).
Avastin is indicated for the first- and second-line treatment of metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy, and for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel. Avastin is being studied worldwide in more than 450 clinical trials and in more than 30 different tumor types. For more information on angiogenesis, visit http://www.gene.com. For full Prescribing Information and Boxed Warnings on Avastin, visit http://www.avastin.com.
Avastin has a well-characterized safety profile in its approved indications. The most serious adverse events associated with Avastin across all trials were gastrointestinal perforation, wound healing complications, hemorrhage, non-GI fistula formation, arterial thromboembolic events, hypertensive crisis, reversible posterior leukoencephalopathy syndrome (RPLS), neutropenia and infection, nephrotic syndrome and congestive heart failure. The most common severe adverse reactions (NCI-CTC Grade 3-5) across clinical trials in metastatic colorectal cancer, NSCLC, and metastatic breast cancer that occurred at a higher incidence (greater than or equal to 2 percent higher rate v. controls) were hypertension, proteinuria, and headache.
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with significant unmet medical needs. The company has headquarters in South San Francisco, California 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 as a treatment option for patients with non-small cell lung cancer and Avastin's safety and efficacy. Such statements are predictions and involve risks and uncertainties such that actual results may differ materially. Actual results may be affected by a number of factors including, but not limited to, unexpected safety, efficacy or manufacturing issues, the need for additional data, data analysis or clinical studies, FDA actions or delays, failure to maintain FDA approval, competition, pricing, reimbursement, the ability to supply product, product withdrawals and new product approvals and launches, and intellectual property or contract rights. Please also refer to the risk factors described in 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 statement in this press release.