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 (AVAiL) demonstrated that Avastin® (bevacizumab), studied at two different doses in combination with gemcitabine and cisplatin chemotherapy, significantly increased the time patients with advanced non-small cell lung cancer (NSCLC) lived without their disease advancing, as defined by progression-free survival (PFS). The investigator-assessed analysis showed similar improvements in PFS among patients in the two Avastin plus gemcitabine and cisplatin chemotherapy arms compared to the chemotherapy alone arm.
Patients receiving 15 mg/kg of Avastin plus gemcitabine and cisplatin chemotherapy experienced a 22 percent improvement in PFS (based on a hazard ratio of 0.82) (p-value = 0.0301) compared to patients receiving chemotherapy alone, and patients receiving 7.5 mg/kg of Avastin plus gemcitabine and cisplatin chemotherapy experienced a 33 percent improvement in PFS (based on a hazard ratio of 0.75) (p-value = 0.0026) compared to patients receiving chemotherapy alone. Broadly overlapping confidence intervals (the range of plausible values that would likely contain the real effect) in the Avastin treatment arms compared to chemotherapy alone suggest the two Avastin arms had a similar treatment effect on PFS when compared with the control arm. No new safety signals for Avastin were observed in the study, and there were no clinically meaningful differences in safety between the two dose arms.
These results were presented today at the American Society of Clinical Oncology (ASCO) 43rd Annual Meeting in Chicago during an oral symposium by Christian Manegold, M.D., professor of Medicine, Heidelberg University, University Medical Center, Mannheim, Germany (Abstract # LBA7514 — Saturday, June 2, 2:45 p.m. CDT). Results for overall survival data, a secondary endpoint of the trial, are not yet mature and will be submitted for presentation at a future medical meeting.
"The data showed an increase in the time patients lived without their cancer growing or spreading when Avastin was administered with cisplatin and gemcitabine chemotherapy, a standard regimen used to treat advanced lung cancer," said Professor Manegold, principal investigator of the study. "The positive AVAiL results add to the body of evidence to support Avastin's use in the most common form of lung cancer."
The U.S. Food and Drug Administration (FDA) approved Avastin for the first-line treatment of unresectable, locally advanced, recurrent or metastatic, non-squamous, NSCLC in October 2006. The approval was based on the positive results of a pivotal U.S. Phase III trial (E4599) that studied a 15 mg/kg dose of Avastin administered every three weeks in combination with carboplatin and paclitaxel, the most commonly used chemotherapy regimen to treat first-line NSCLC in the U.S. The trial showed a 25 percent improvement in overall survival for Avastin plus chemotherapy compared to chemotherapy alone and an investigator-assessed 52 percent improvement in PFS (hazard ratio = 0.66). Avastin is the first FDA-approved therapy to extend survival beyond one year in patients with advanced NSCLC in a Phase III trial and the first therapy in a decade to improve on standard first-line treatment for advanced lung cancer.
"We believe some U.S. physicians will consider these new data when making decisions about how to use Avastin in their practices, while others will prescribe Avastin based on the dose and chemotherapy combination that showed improved overall survival in the U.S. pivotal study," said Hal Barron, M.D., senior vice president, Development and chief medical officer. "This study is important for patients and physicians because it provides information about Avastin's potential efficacy with a second chemotherapy combination in lung cancer."
According to the American Cancer Society (ACS), lung cancer is the single largest cause of cancer death among men and women in the U.S. and is responsible for nearly 30 percent of cancer deaths each year. The ACS estimates that more than 213,000 Americans will be diagnosed with lung cancer and 160,000 Americans will die of the disease in 2007.
The 22 and 33 percent improvements in PFS respectively in the 15 mg/kg and 7.5 mg/kg Avastin treatment arms can also be referred to as 18 and 25 percent reductions in risk of cancer progression or death, as calculated by the hazard ratios. Median PFS was 6.5 months in the 15 mg/kg Avastin plus chemotherapy arm, 6.7 months in the 7.5 mg/kg Avastin plus chemotherapy arm and 6.1 months in the gemcitabine/cisplatin chemotherapy alone arm. The tumor response rates in patients with measurable disease at baseline were 30 percent (101/332) in the 15 mg/kg Avastin plus chemotherapy arm and 34 percent (110/323) in the 7.5 mg/kg Avastin plus chemotherapy arm, compared to 20 percent (65/324) in the chemotherapy alone arm. Duration of tumor response was 6.1 months in both Avastin-containing arms compared to 4.7 months in the chemotherapy alone arm.
Safety was similar to previous studies of Avastin in NSCLC. In AVAiL, the most common severe adverse events were neutropenia, thrombocytopenia and anemia. Severe (Grade 3 or greater) neutropenia occurred at 36 and 40 percent respectively in the 15 mg/kg and 7.5 mg/kg Avastin arms, compared to 32 percent in the chemotherapy alone arm. Severe thrombocytopenia occurred at 23 and 27 percent respectively in the 15 mg/kg and 7.5 mg/kg Avastin arms, compared to 23 percent in the chemotherapy alone arm. Grade 3 or greater anemia was 10 percent in both Avastin arms, compared to 14 percent in the chemotherapy alone arm.
Grade 3 or greater pulmonary hemorrhage occurred at 0.9 percent in the 15 mg/kg Avastin arm and 1.5 percent in the 7.5mg/kg Avastin arm, compared to 0.6 percent in the chemotherapy alone arm. Bleeding occurred at 4 percent in both Avastin arms, compared to 2 percent in the chemotherapy alone arm. Severe venous thromboembolic events occurred in 7 percent of patients in both Avastin arms, compared to 6 percent of patients in the chemotherapy alone arm. Severe ischemic events occurred at 3 and 2 percent respectively in 15 mg/kg and 7.5 mg/kg Avastin arms, compared to 5 percent in the chemotherapy alone arm. Severe hypertension occurred at 9 and 6 percent respectively in the 15 mg/kg and 7.5 mg/kg Avastin arms, compared to 2 percent in the chemotherapy alone arm.
AVAiL was an international study that enrolled 1,044 patients with previously untreated, advanced, non-squamous, NSCLC. 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. The primary endpoint was PFS, defined as the time from randomization to the first event of progression or death. Secondary endpoints included overall survival, time to treatment failure and safety.
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 first approved Avastin on February 26, 2004, as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy. In addition to the supplemental indication in advanced NSCLC, 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.
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 physician practices with respect to Avastin dosing. Such statements are predictions and involve risks and uncertainties such that actual results may differ materially. Among other things, physician practices with respect to Avastin dosing may be affected by a number of factors, including unexpected safety, efficacy or manufacturing issues, regulatory developments, pricing, reimbursement, competition, the ability to supply product or new product approvals and launches. 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.