Joe
05-31-2008, 07:46 AM
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</TD></TR><TR><TD class=body>Saturday, May 31, 2008
</TD></TR><TR><TD class=subHeader>
Second Phase III Study of Avastin Plus Chemotherapy Shows Improved Progression-Free Survival in Women With Advanced HER2-Negative Breast Cancer
</TD></TR><TR><TD class=subHeaderNews align=middle>
-- Positive AVADO Results Support Efficacy and Safety of Avastin in First-Line Metastatic Breast Cancer --
</TD></TR><TR><TD class=body>
Chicago -- May 31, 2008 -- Genentech, Inc. (NYSE: DNA) today announced that Avastin® (bevacizumab), in combination with docetaxel chemotherapy, significantly increased the time women with metastatic breast cancer receiving first-line therapy lived without their disease advancing, as defined by the primary endpoint of progression-free survival (PFS). In this Roche-sponsored, placebo-controlled Phase III trial (AVADO), two dose levels of Avastin in combination with docetaxel chemotherapy showed a statistically significant improvement in PFS compared to docetaxel chemotherapy alone, according to an investigator-assessed analysis. No new safety signals for Avastin were observed in the study.
The results were featured today during a press briefing at the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) and will be presented tomorrow by David Miles, M.D., medical oncologist, Mount Vernon Hospital, United Kingdom (Abstract # LBA1011 – June 1, 2008 at 8:30 a.m. CDT in E Hall D1).
"These results build upon previous data and expand our understanding of Avastin’s efficacy and safety when combined with another commonly used taxane chemotherapy," said Dr. David Miles, principal investigator of the study. "Importantly, this study supports that Avastin can be used with taxane-based chemotherapy to provide a meaningful benefit for patients with advanced HER2-negative breast cancer."
Genentech is required to submit to the U.S. Food and Drug Administration (FDA) by mid-2009 the results of AVADO and RIBBON I, a third Phase III study in first-line metastatic breast cancer. Results for the RIBBON I study are expected later this year.
The pre-specified analysis of AVADO for U.S. regulatory purposes showed that Avastin combined with chemotherapy improved PFS by up to 64 percent (hazard ratio of 0.61; p<0.0001) in the 15 mg/kg treatment arm and by up to 45 percent (hazard ratio of 0.69; p=0.0035) in the 7.5 mg/kg treatment arm, compared to chemotherapy alone. Overall response rate, a secondary endpoint, was also positive and supported the PFS benefit observed in this study. After one year, 83 percent and 78 percent of patients were alive in the 15 mg/kg and 7.5 mg/kg Avastin treatment arms, compared to 73 percent of patients receiving chemotherapy alone.
"The totality of the AVADO results, including positive primary and secondary endpoints and reassurances of safety, support the benefit of Avastin in extending the time women lived without their disease progressing when combined with chemotherapy as a first-line treatment," said Susan Desmond-Hellmann, M.D., M.P.H., president, Product Development. "We are committed to fully evaluating Avastin’s efficacy and safety in metastatic breast cancer and anticipate the results of a third Phase III trial later this year."
About AVADO
AVADO was an international, multicenter, randomized, double-blind, placebo-controlled clinical trial that enrolled 736 patients with locally recurrent or metastatic HER2-negative breast cancer who had not received chemotherapy for their metastatic disease. Patients were randomized to one of two doses of Avastin (15 mg/kg or 7.5 mg/kg) or placebo given every three weeks in combination with docetaxel chemotherapy for a maximum of nine cycles. Patients discontinuing docetaxel for toxicity or after nine cycles were to continue on Avastin only or placebo until disease progression. The AVADO study was not designed to compare the two dose levels of Avastin.
In the 15 mg/kg and 7.5 mg/kg Avastin treatment arms, the 64 percent and 45 percent improvements in PFS observed can also be referred to as 39 percent and 31 percent reductions in the risk of cancer progression or death. Median PFS was 8.8 months, 8.7 months and 8.0 months in the 15 mg/kg and 7.5 mg/kg Avastin plus chemotherapy arms and the chemotherapy alone arm, respectively. Overall response rates were 63 percent (p=0.0001) and 55 percent (p=0.0295) in the 15 mg/kg and 7.5 mg/kg Avastin plus chemotherapy arms, compared to 44 percent in the chemotherapy alone arm.
The study protocol specified analyses for overall survival at the time of primary endpoint analysis and 24 months after the last patient was enrolled. The final analysis for overall survival is expected in 2009. Hazard ratios for the preliminary analysis of overall survival are 0.68 and 0.92 for the 15 mg/kg and 7.5 mg/kg Avastin arms, respectively. These initial results for overall survival are not statistically significant and are based on early information.
<TABLE cellSpacing=0 cellPadding=5 width=550 border=1><TBODY><TR><TD align=middle>Efficacy Results</TD><TD align=middle>15 mg/kg Avastin + docetaxel<SUP>1</SUP></TD><TD align=middle>7.5 mg/kg Avastin + docetaxel<SUP>1</SUP></TD><TD align=middle>Placebo +
docetaxel<SUP>1</SUP></TD></TR><TR vAlign=top><TD vAlign=top>Progression-Free Survival (PFS)<SUP>2</SUP>
Overall PFS
Improvement
Risk Reduction
Hazard Ratio
p-value</TD><TD vAlign=top align=middle>
64%
39%
0.61
p<0.0001</TD><TD vAlign=top align=middle>
45%
31%
0.69
p=0.0035</TD><TD vAlign=top align=middle>
N/A</TD></TR><TR vAlign=top><TD>Median PFS (months)</TD><TD align=middle>8.8</TD><TD align=middle>8.7</TD><TD align=middle>8.0</TD></TR><TR vAlign=top><TD>Overall Response Rate (%)<SUP>3
</SUP>p-value</TD><TD align=middle>63
p=0.0001</TD><TD align=middle>55
p=0.0295</TD><TD align=middle>44
</TD></TR><TR><TD>1-Year Survival Rate (%)</TD><TD align=middle>83</TD><TD align=middle>78</TD><TD align=middle>73</TD></TR><TR><TD>Overall Survival (not mature)
Hazard Ratio</TD><TD align=middle>
0.68</TD><TD align=middle>
0.92</TD><TD align=middle>
N/A</TD></TR></TBODY></TABLE>
<SUP>1</SUP> Each Avastin + docetaxel arm was studied against placebo + docetaxel. The study was not designed to compare the two Avastin arms.
<SUP>2</SUP> Pre-specified primary endpoint analysis for U.S. regulatory purposes.
<SUP>3</SUP> Among patients with measurable disease at baseline.
The AVADO study provided a comprehensive safety assessment of the Avastin and docetaxel combination by using a placebo control arm and collecting Grade 1 to 5 adverse events in all arms of the study. The most common severe adverse events were generally consistent with those observed in a previous Phase III study of Avastin in metastatic breast cancer.
<TABLE cellPadding=5 width="100%" border=1><TBODY><TR><TD width="28%">Safety Results
% (n)</TD><TD align=middle width="24%">15 mg/kg Avastin
+ docetaxel</TD><TD align=middle width="24%">7.5 mg/kg Avastin
+ docetaxel</TD><TD align=middle width="24%">Placebo
+ docetaxel</TD></TR><TR><TD>Grade 3-5 Adverse Events (AEs)</TD><TD align=middle>74% (183/247)</TD><TD align=middle>75% (187/250)</TD><TD align=middle>67% (156/233)</TD></TR><TR><TD>≥Grade 3 Hypertension</TD><TD align=middle>3.2% (8/247)</TD><TD align=middle>0.4% (1/250)</TD><TD align=middle>1.3% (3/233)</TD></TR><TR><TD>≥Grade 3 Febrile neutropenia</TD><TD align=middle>16.6% (41/247)</TD><TD align=middle>15.2% (38/250)</TD><TD align=middle>12.0% (28/233)</TD></TR><TR><TD>≥Grade 3 Skin exfoliation</TD><TD align=middle>1.2% (3/247)</TD><TD align=middle>2.4% (6/250)</TD><TD align=middle>0% (0/233)</TD></TR><TR><TD>≥Grade 3 Mucosal inflammation</TD><TD align=middle>4.9% (12/247)</TD><TD align=middle>4.0% (10/250)</TD><TD align=middle>0.4% (1/233)</TD></TR><TR><TD>Grade 5 AEs (deaths during blinded study treatment not due to breast cancer)</TD><TD align=middle>1.6% (4/247)</TD><TD align=middle>1.6% (4/250)</TD><TD align=middle>2.6% (6/233)</TD></TR></TBODY></TABLE>
About Breast Cancer
Breast cancer is the second most common form of cancer and second leading cause of cancer deaths among American women. According to the American Cancer Society, an estimated 182,000 women will be diagnosed with breast cancer and approximately 40,000 will die from the disease in the U.S. in 2008. Genentech estimates that 75 percent of women with newly diagnosed metastatic breast cancer are HER2-negative.
About Avastin
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).
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. For more information on angiogenesis, visit http://www.gene.com (http://www.gene.com/). For full Prescribing Information and Boxed Warnings on Avastin, visit http://www.avastin.com (http://www.avastin.com/).
Avastin Safety
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 vs. controls) were hypertension, proteinuria and headache.
About Genentech
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines for 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 (http://www.gene.com/). <CENTER>###</CENTER>This press release contains forward-looking statements regarding the safety and efficacy of Avastin, the benefit of Avastin for patients, and the timing of data availability. 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.
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</TD></TR><TR><TD class=body>Saturday, May 31, 2008
</TD></TR><TR><TD class=subHeader>
Second Phase III Study of Avastin Plus Chemotherapy Shows Improved Progression-Free Survival in Women With Advanced HER2-Negative Breast Cancer
</TD></TR><TR><TD class=subHeaderNews align=middle>
-- Positive AVADO Results Support Efficacy and Safety of Avastin in First-Line Metastatic Breast Cancer --
</TD></TR><TR><TD class=body>
Chicago -- May 31, 2008 -- Genentech, Inc. (NYSE: DNA) today announced that Avastin® (bevacizumab), in combination with docetaxel chemotherapy, significantly increased the time women with metastatic breast cancer receiving first-line therapy lived without their disease advancing, as defined by the primary endpoint of progression-free survival (PFS). In this Roche-sponsored, placebo-controlled Phase III trial (AVADO), two dose levels of Avastin in combination with docetaxel chemotherapy showed a statistically significant improvement in PFS compared to docetaxel chemotherapy alone, according to an investigator-assessed analysis. No new safety signals for Avastin were observed in the study.
The results were featured today during a press briefing at the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) and will be presented tomorrow by David Miles, M.D., medical oncologist, Mount Vernon Hospital, United Kingdom (Abstract # LBA1011 – June 1, 2008 at 8:30 a.m. CDT in E Hall D1).
"These results build upon previous data and expand our understanding of Avastin’s efficacy and safety when combined with another commonly used taxane chemotherapy," said Dr. David Miles, principal investigator of the study. "Importantly, this study supports that Avastin can be used with taxane-based chemotherapy to provide a meaningful benefit for patients with advanced HER2-negative breast cancer."
Genentech is required to submit to the U.S. Food and Drug Administration (FDA) by mid-2009 the results of AVADO and RIBBON I, a third Phase III study in first-line metastatic breast cancer. Results for the RIBBON I study are expected later this year.
The pre-specified analysis of AVADO for U.S. regulatory purposes showed that Avastin combined with chemotherapy improved PFS by up to 64 percent (hazard ratio of 0.61; p<0.0001) in the 15 mg/kg treatment arm and by up to 45 percent (hazard ratio of 0.69; p=0.0035) in the 7.5 mg/kg treatment arm, compared to chemotherapy alone. Overall response rate, a secondary endpoint, was also positive and supported the PFS benefit observed in this study. After one year, 83 percent and 78 percent of patients were alive in the 15 mg/kg and 7.5 mg/kg Avastin treatment arms, compared to 73 percent of patients receiving chemotherapy alone.
"The totality of the AVADO results, including positive primary and secondary endpoints and reassurances of safety, support the benefit of Avastin in extending the time women lived without their disease progressing when combined with chemotherapy as a first-line treatment," said Susan Desmond-Hellmann, M.D., M.P.H., president, Product Development. "We are committed to fully evaluating Avastin’s efficacy and safety in metastatic breast cancer and anticipate the results of a third Phase III trial later this year."
About AVADO
AVADO was an international, multicenter, randomized, double-blind, placebo-controlled clinical trial that enrolled 736 patients with locally recurrent or metastatic HER2-negative breast cancer who had not received chemotherapy for their metastatic disease. Patients were randomized to one of two doses of Avastin (15 mg/kg or 7.5 mg/kg) or placebo given every three weeks in combination with docetaxel chemotherapy for a maximum of nine cycles. Patients discontinuing docetaxel for toxicity or after nine cycles were to continue on Avastin only or placebo until disease progression. The AVADO study was not designed to compare the two dose levels of Avastin.
In the 15 mg/kg and 7.5 mg/kg Avastin treatment arms, the 64 percent and 45 percent improvements in PFS observed can also be referred to as 39 percent and 31 percent reductions in the risk of cancer progression or death. Median PFS was 8.8 months, 8.7 months and 8.0 months in the 15 mg/kg and 7.5 mg/kg Avastin plus chemotherapy arms and the chemotherapy alone arm, respectively. Overall response rates were 63 percent (p=0.0001) and 55 percent (p=0.0295) in the 15 mg/kg and 7.5 mg/kg Avastin plus chemotherapy arms, compared to 44 percent in the chemotherapy alone arm.
The study protocol specified analyses for overall survival at the time of primary endpoint analysis and 24 months after the last patient was enrolled. The final analysis for overall survival is expected in 2009. Hazard ratios for the preliminary analysis of overall survival are 0.68 and 0.92 for the 15 mg/kg and 7.5 mg/kg Avastin arms, respectively. These initial results for overall survival are not statistically significant and are based on early information.
<TABLE cellSpacing=0 cellPadding=5 width=550 border=1><TBODY><TR><TD align=middle>Efficacy Results</TD><TD align=middle>15 mg/kg Avastin + docetaxel<SUP>1</SUP></TD><TD align=middle>7.5 mg/kg Avastin + docetaxel<SUP>1</SUP></TD><TD align=middle>Placebo +
docetaxel<SUP>1</SUP></TD></TR><TR vAlign=top><TD vAlign=top>Progression-Free Survival (PFS)<SUP>2</SUP>
Overall PFS
Improvement
Risk Reduction
Hazard Ratio
p-value</TD><TD vAlign=top align=middle>
64%
39%
0.61
p<0.0001</TD><TD vAlign=top align=middle>
45%
31%
0.69
p=0.0035</TD><TD vAlign=top align=middle>
N/A</TD></TR><TR vAlign=top><TD>Median PFS (months)</TD><TD align=middle>8.8</TD><TD align=middle>8.7</TD><TD align=middle>8.0</TD></TR><TR vAlign=top><TD>Overall Response Rate (%)<SUP>3
</SUP>p-value</TD><TD align=middle>63
p=0.0001</TD><TD align=middle>55
p=0.0295</TD><TD align=middle>44
</TD></TR><TR><TD>1-Year Survival Rate (%)</TD><TD align=middle>83</TD><TD align=middle>78</TD><TD align=middle>73</TD></TR><TR><TD>Overall Survival (not mature)
Hazard Ratio</TD><TD align=middle>
0.68</TD><TD align=middle>
0.92</TD><TD align=middle>
N/A</TD></TR></TBODY></TABLE>
<SUP>1</SUP> Each Avastin + docetaxel arm was studied against placebo + docetaxel. The study was not designed to compare the two Avastin arms.
<SUP>2</SUP> Pre-specified primary endpoint analysis for U.S. regulatory purposes.
<SUP>3</SUP> Among patients with measurable disease at baseline.
The AVADO study provided a comprehensive safety assessment of the Avastin and docetaxel combination by using a placebo control arm and collecting Grade 1 to 5 adverse events in all arms of the study. The most common severe adverse events were generally consistent with those observed in a previous Phase III study of Avastin in metastatic breast cancer.
<TABLE cellPadding=5 width="100%" border=1><TBODY><TR><TD width="28%">Safety Results
% (n)</TD><TD align=middle width="24%">15 mg/kg Avastin
+ docetaxel</TD><TD align=middle width="24%">7.5 mg/kg Avastin
+ docetaxel</TD><TD align=middle width="24%">Placebo
+ docetaxel</TD></TR><TR><TD>Grade 3-5 Adverse Events (AEs)</TD><TD align=middle>74% (183/247)</TD><TD align=middle>75% (187/250)</TD><TD align=middle>67% (156/233)</TD></TR><TR><TD>≥Grade 3 Hypertension</TD><TD align=middle>3.2% (8/247)</TD><TD align=middle>0.4% (1/250)</TD><TD align=middle>1.3% (3/233)</TD></TR><TR><TD>≥Grade 3 Febrile neutropenia</TD><TD align=middle>16.6% (41/247)</TD><TD align=middle>15.2% (38/250)</TD><TD align=middle>12.0% (28/233)</TD></TR><TR><TD>≥Grade 3 Skin exfoliation</TD><TD align=middle>1.2% (3/247)</TD><TD align=middle>2.4% (6/250)</TD><TD align=middle>0% (0/233)</TD></TR><TR><TD>≥Grade 3 Mucosal inflammation</TD><TD align=middle>4.9% (12/247)</TD><TD align=middle>4.0% (10/250)</TD><TD align=middle>0.4% (1/233)</TD></TR><TR><TD>Grade 5 AEs (deaths during blinded study treatment not due to breast cancer)</TD><TD align=middle>1.6% (4/247)</TD><TD align=middle>1.6% (4/250)</TD><TD align=middle>2.6% (6/233)</TD></TR></TBODY></TABLE>
About Breast Cancer
Breast cancer is the second most common form of cancer and second leading cause of cancer deaths among American women. According to the American Cancer Society, an estimated 182,000 women will be diagnosed with breast cancer and approximately 40,000 will die from the disease in the U.S. in 2008. Genentech estimates that 75 percent of women with newly diagnosed metastatic breast cancer are HER2-negative.
About Avastin
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).
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. For more information on angiogenesis, visit http://www.gene.com (http://www.gene.com/). For full Prescribing Information and Boxed Warnings on Avastin, visit http://www.avastin.com (http://www.avastin.com/).
Avastin Safety
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 vs. controls) were hypertension, proteinuria and headache.
About Genentech
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines for 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 (http://www.gene.com/). <CENTER>###</CENTER>This press release contains forward-looking statements regarding the safety and efficacy of Avastin, the benefit of Avastin for patients, and the timing of data availability. 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.
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