Thursday, May 15, 2008
South San Francisco, Calif -- May 15, 2008 --Genentech, Inc. (NYSE: DNA) today provided an overview of several clinical studies of Avastin® in multiple types of cancer that will be presented during the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) taking place May 30 to June 3 in Chicago. The company also provided an update regarding the availability of anticipated final results for an ongoing non-company sponsored Phase III study of Avastin in early-stage colon cancer (C-08).
Genentech has revised its timeline forecast for availability of final efficacy and safety results for the C-08 study from 2010 to 2009. The study, involving more than 2,700 patients, is being conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) and is sponsored by the National Cancer Institute (NCI). The new timeline forecast is based primarily on the rate of NSABP's data collection, rapid patient enrollment, and a higher than planned number of Stage III patients. These updates do not change Genentech's assessment of the study's probability of success. An independent data monitoring committee (DMC) for the study assesses safety and efficacy every six months and recommends whether adequate information is available to stop or continue the trial. Genentech has been informed that the last interim assessment took place in Q2 2008 and the DMC recommended that the trial continue as planned.
An early look at safety results from the C-08 study will be among the more than 185 scientific abstracts regarding Avastin that will be published or presented at the ASCO meeting. Avastin studies will be featured in 11 oral presentations, including a late-breaker presentation of AVADO, a Roche-sponsored Phase III study of Avastin plus chemotherapy as a first-line treatment for metastatic breast cancer. Analyses of data from the AVADO study will be available on May 31, 2008.
Encouraging results will also be presented from a Phase II study of Avastin in glioblastoma multiforme (GBM), an aggressive type of brain cancer. In addition, several studies will be presented that provide further support of Avastin's safety as a first-line treatment for patients with advanced, non-squamous, non-small cell lung cancer (NSCLC) and metastatic colorectal cancer.
"The Avastin development program represents one of the most comprehensive undertakings in cancer research since the development of chemotherapy," said Susan Desmond-Hellmann, M.D., M.P.H., president, Product Development. "The breadth of Avastin data to be presented at ASCO reflects our commitment to understand if Avastin can provide benefit in different types of cancer and in combination with other therapies, to ultimately provide physicians with more effective treatments for their patients."
Early-Stage Colon Cancer
Initial Safety Report of National Surgical Adjuvant Breast and Bowel Project (NSABP) C-08, a Randomized Phase III Study of Modified 5-Fluorouracil/Leucovorin and Oxaliplatin (mFOLFOX6) With or Without Bevacizumab in the Adjuvant Treatment of Patients With Stage II/III Colon Cancer (Abstract # 4006) - Saturday, May 31, 2008, 3:15 p.m. - 3:30 p.m. CDT; E Hall D1
A preliminary interim safety analysis of data from a randomized, multicenter Phase III clinical study (C-08) evaluating Avastin plus FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) chemotherapy compared to FOLFOX chemotherapy alone following surgery will be presented. The study includes more than 2,700 patients with early-stage (II and III) colon cancer.
The interim safety analysis showed no new or unexpected safety events in the Avastin arm and supports the National Surgical Adjuvant Breast and Bowel Project's (NSABP) decision to continue this study as planned. The incidence of non-cancer-related deaths was similar between the treatment arms and consistent with prior Phase III adjuvant colon cancer trials. No significant increases in gastrointestinal (GI) perforation, hemorrhage, arterial or venous thrombotic events or deaths were observed in the Avastin arm. At the time of abstract submission, analysis showed that Grade 3 or greater events that occurred more often in the Avastin plus chemotherapy arm included hypertension (12.7 percent vs. 1.8 percent), wound healing complications (1.7 percent vs. 0.3 percent) and pain (6.9 percent vs. 3.4 percent). The study is being conducted by the NSABP and is sponsored by the National Cancer Institute (NCI). Efficacy data are not yet available.
"We are pleased that no significant safety concerns have been observed to date in this important study of Avastin in early-stage colon cancer," said David Schenkein, M.D., senior vice president, Clinical Hematology and Oncology. "Due to the high cure rate for early-stage colon cancer, there is a lower acceptance of risk related to potential new therapies in the adjuvant treatment setting."
In addition to the C-08 safety study in early-stage colon cancer, results from a large observational study (Abstracts #4103, #4026) will be presented that provide information supporting Avastin's efficacy and safety in metastatic colorectal cancer.
Avastin and Biomarkers in Colorectal Cancer
Data regarding Avastin and biomarkers will not be presented at ASCO. Previously-published analyses suggest that Avastin's benefit in advanced colorectal cancer is not affected by mutations in genes such as K-ras, p53 and b-raf. An analysis from Avastin's pivotal study in metastatic colorectal cancer showed an improvement in median survival for patients with both mutant and wild-type K-ras genes (HR=0.69 and HR=0.58, respectively) (Ince et al. 2005, J Natl Cancer Inst, 97:981-9).
Avastin is designed to inhibit the vascular endothelial growth factor (VEGF) protein, the only angiogenic growth factor known to be present throughout the entire tumor life cycle.
Recurrent Glioblastoma Multiforme
A Phase II, Randomized, Non-Comparative Clinical Trial of the Effect of Bevacizumab Alone or in Combination With Irinotecan on Six-Month Progression-Free Survival in Recurrent, Treatment-Refractory Glioblastoma (Abstract #2010b) - Monday, June 2, 2008, 9:30 a.m. - 9:45 a.m. CDT; S406 (Vista Room)
Data from a Phase II randomized clinical study of Avastin administered alone or in combination with irinotecan chemotherapy showed encouraging median survival, six-month progression-free survival and objective response rates in patients with relapsed glioblastoma multiforme (GBM), the most common and aggressive type of brain cancer. This will be the first presentation of median survival results from the study.
"Avastin, both as a single agent and in combination with irinotecan chemotherapy, may improve survival compared to what would be normally expected for this devastating disease," said Timothy Cloughesy, M.D., director, Neuro-Oncology Program of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles. "According to historical estimates, only 15 percent of patients with relapsed glioblastoma multiforme would be expected to live without their cancer advancing within six months."
Results to be presented at the meeting show that median survival was 9.2 months in the Avastin-only arm and 8.7 months in the Avastin and irinotecan arm. As assessed by independent radiological review, 43 percent of GBM patients treated with Avastin alone and 50 percent of patients treated with Avastin in combination with chemotherapy lived without the disease advancing within six months. Tumor response was observed in 28 percent (24/85) of patients treated with Avastin alone and 38 percent (31/82) of patients treated with Avastin in combination with chemotherapy.
Most adverse events related to Avastin in this trial appeared to be similar to those previously reported in other studies of Avastin. The most common severe (Grade 3 or greater) toxicities in the Avastin-only arm were hypertension (8 percent, 7/84) and convulsion (6 percent, 5/84). The most common severe adverse events in the Avastin plus chemotherapy arm were convulsion (14 percent, 11/79), fatigue (9 percent, 7/79) and neutropenia (9 percent, 7/79). One patient in the Avastin plus chemotherapy arm experienced a Grade 4 intracranial hemorrhage. There were two deaths associated with adverse events in the Avastin-only arm and one death associated with an adverse event in the Avastin plus chemotherapy arm.
Genentech plans to submit a supplemental biologics license application for Avastin to the U.S. Food and Drug Administration (FDA) for the treatment of relapsed GBM in the second half of 2008. The company also expects to initiate a global Phase III study of Avastin in the first-line treatment of GBM in 2008.
Key Studies About Avastin Safety in Advanced NSCLC
Preliminary Treatment Patterns and Safety Outcomes for Non-Small Cell Lung Cancer From ARIES, a Bevacizumab Treatment Observational Cohort Study (Abstract #8077) - Sunday, June 1, 2008, 2:00 p.m. - 6:00 p.m. CDT; S Hall A1
Safety of Bevacizumab-Based Therapy as First-Line Treatment of Patients With Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer (SAiL) (Abstract #8085) - Sunday, June 1, 2008, 2:00 p.m. - 6:00 p.m. CDT; S Hall A1
Safety of First-Line Bevacizumab-Based Therapy With Concomitant Cardiovascular or Anticoagulation Medication in Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer in MO19390 (SAiL) (Abstract #8049) - Sunday, June 1, 2008, 2:00 p.m. - 6:00 p.m. CDT; S Hall A1
Analyses will be presented from two observational studies involving more than 2,000 patients that support Avastin safety in patients with advanced, non-squamous, non-small cell lung cancer (NSCLC). Importantly, the studies provide Avastin safety data from lung cancer patients with brain metastases, the elderly or patients who are being treated with anti-hypertensive agents or blood thinning medications, who are often excluded from clinical trials.
Safety results from 1,031 patients in the ARIES study (Abstract #8077) showed no new or unexpected adverse events were observed in this "real-world" patient population and a low incidence of targeted serious adverse events. Analysis to be presented at the meeting show that blood clots in the veins (venous thrombotic events) and Grade 3/4 bleeding (non-pulmonary) were reported in 2.4 percent (25/1031) and 1.2 percent (12/1031) of patients, respectively. Severe pulmonary hemorrhage occurred in less than 1 percent (5/1031) of patients.
At the time of abstract submission, an analysis of data from 1,065 patients in the SAiL study (Abstracts #8085, #8049) showed a low incidence of serious adverse events related to Avastin (6 percent, 64/1065), and the majority of all serious adverse events in the study (76 percent, 299/396) resolved or improved. Grade 3/4 hypertension was reported in 2.7 percent (29/1065) of patients, and the management of hypertension was not impaired in patients receiving Avastin. In the study, treatment with Avastin was not associated with central nervous system hemorrhages in patients with brain metastases. Updated data from SAiL will be presented at the meeting.
All Oral Presentations of Avastin Studies
Initial Safety Report of NSABP C-08, a Randomized Phase III Study of Modified 5-Fluorouracil/Leucovorin and Oxaliplatin (mFOLFOX6) With or Without Bevacizumab in the Adjuvant Treatment of Patients With Stage II/III Colon Cancer (Abstract #4006) - Saturday, May 31, 3:15 p.m. - 3:30 p.m. CDT; E Hall D1
Update on AVOREN Trial in Metastatic Renal Cell Carcinoma: Efficacy and Safety in Subgroups of Patients and Pharmacokinetic Analysis (Abstract #5025) - Saturday, May 31, 4:15 p.m. - 4:30 p.m. CDT; W375e
Intermittent Oxaliplatin Administration and Time-to-Treatment-Failure in Metastatic Colorectal Cancer: Final Results of the Phase III CONcePT Trial (Abstract #4010) - Saturday, May 31, 4:30 p.m. - 4:45 p.m. CDT; E Hall D1
Randomized Phase III Study of Capecitabine, Oxaliplatin, and Bevacizumab With or Without Cetuximab in Advanced Colorectal Cancer, the CAIRO2 Study of the Dutch Colorectal Cancer Group (Abstract #LBA4011) - Saturday, May 31, 4:45 p.m. - 5:00 p.m. CDT; E Hall D1
Radiofrequency Ablation Combined With Chemotherapy for Unresectable Colorectal Liver Metastases: Interim Results of a Randomized Phase II Study of the EORTC-NCRI CCSG-ALM Intergroup 40004 (Abstract #4012) - Saturday, May 31, 5:15 p.m. - 5:30 p.m. CDT; E Hall D1
Combination Therapy With Temozolomide and Bevacizumab in the Treatment of Hemangiopericytoma/Malignant Solitary Fibrous Tumor (Abstract #10512) - Saturday, May 31, 5:25 p.m. - 5:40 p.m. CDT; W375b
Randomized, Double-Blind, Placebo-Controlled, Phase III Study of Bevacizumab With Docetaxel or Docetaxel With Placebo as First-Line Therapy for Patients With Locally Recurrent or Metastatic Breast Cancer: AVADO (Abstract #LBA1011) - Sunday, June 1, 8:30 a.m. - 8:45 a.m. CDT; E Hall D1
WNK1 Haplotypes and Bevacizumab-Induced Hypertension (Abstract #11003) - Monday, June 2, 8:00 a.m. - 8:15 a.m. CDT; W375b
Role of a Second Chemotherapy in Recurrent Malignant Glioma Patients who Progress on a Bevacizumab-Containing Regimen (Abstract #2008) - Monday, June 2, 9:00 a.m. - 9:15 a.m. CDT; S406 (Vista Room)
A Phase II, Randomized, Non-Comparative Clinical Trial of the Effect of Bevacizumab Alone or in Combination With Irinotecan on Six-Month Progression-Free Survival in Recurrent, Treatment-Refractory Glioblastoma (Abstract #2010b) - Monday, June 2, 9:30 a.m. - 9:45 a.m. CDT; S406 (Vista Room)
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase III Trial to Evaluate the Efficacy and Safety of Adding Bevacizumab to Erlotinib and Gemcitabine in Patients With Metastatic Pancreatic Cancer (AVITA) (Abstract #4507) - Monday, June 2, 3:45 p.m. - 4:00 p.m. CDT; E Hall D2
This press release contains forward-looking statements regarding the timing of data availability and probability of success for clinical studies of Avastin, the submission of a biologics license application (BLA) for Avastin, the initiation of a clinical study of Avastin, Avastin's efficacy and safety in metastatic colorectal cancer, and the potential of Avastin to treat different types of cancer. 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, difficulty enrolling patients in clinical trials, the need for additional data, data analysis or clinical studies, BLA preparation, 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.