Positive results from Genentech Avastin plus temozolomide Phase III study on glioblastoma

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced results from the positive Phase III AVAglio study. The study showed Avastin^® (bevacizumab) in combination with radiation and temozolomide chemotherapy reduced the risk of cancer worsening or death (progression-free survival; PFS) by 36 percent compared to radiation and temozolomide chemotherapy plus placebo (HR=0.64; p<0.0001) in people with newly diagnosed glioblastoma, the most common and aggressive form of primary brain cancer. PFS assessed by trial investigators was a co-primary endpoint for the study. The interim results for overall survival (OS), the other co-primary endpoint, did not reach statistical significance (HR=0.89; p=0.2135). Final data on OS are expected in 2013. The data were presented today at the 17^th Annual Meeting of the Society for Neuro-Oncology in Washington, D.C.

No new safety findings were observed in the AVAglio study and adverse events were consistent with those seen in previous trials of Avastin across tumor types for approved indications. Adverse events of special interest (all Grades) that occurred more often in the Avastin arm compared to the radiation and chemotherapy arm (>2 percent increased incidence) were bleeding in mucous/skin linings (26.7 percent vs. 8.9 percent) or other regions of the body excluding the brain (11.6 percent vs. 8.1 percent), high blood pressure (37.5 percent vs. 13 percent), too much protein in the urine (proteinuria; 14 percent vs. 4 percent) and blood clots (arterial thromboembolic; 5.0 percent vs. 1.6 percent).

Avastin is currently approved in the United States under the U.S. Food and Drug Administration's (FDA) accelerated approval program for the treatment of adults with glioblastoma who have progressive disease following prior therapy. In glioblastoma, it is approved for use as a single therapy and not in combination with other therapies. The effectiveness of Avastin is based on improvement in objective response rate. Currently, no data are available from randomized controlled trials demonstrating improvement in disease-related symptoms or increased survival with Avastin in glioblastoma.

"People with newly diagnosed glioblastoma have few treatment options and need new medicines," said Hal Barron M.D., chief medical officer and head of Global Product Development. "An important outcome from the AVAglio study was that patients who received Avastin plus radiation and chemotherapy lived significantly longer without their disease getting worse, and we plan to discuss these data with regulatory authorities."

The results of the Phase III AVAglio trial were presented in Plenary Session 5 by Professor Olivier Chinot, AVAglio principal investigator, President of Association des Neuro-Oncologue d'Expression Française (ANOEF), and head of the neuro-oncology department, University Hospital Timone, Marseille, France.

AVAglio Study Results

Primary endpoints:

• The 36 percent reduction in the risk of disease worsening or death can also be referred to as a 56 percent improvement in PFS (HR=0.64; p<0.0001).
• A 4.4 month improvement in median PFS was observed when people with newly diagnosed glioblastoma received Avastin in combination with radiation and chemotherapy compared to those who received radiation and chemotherapy plus placebo (10.6 months vs. 6.2 months, respectively).
• Interim results for OS did not reach statistical significance (HR=0.89; p=0.2135). Final data on OS are expected in 2013.

Secondary endpoints:

• An independent review committee assessment of PFS showed a 39 percent reduction in the risk of disease worsening or death, which can also be referred to as a 64 percent improvement in PFS (HR=0.61; p<0.0001). This was consistent with the magnitude of benefit assessed by the trial investigators.
• The one-year survival rate was 66 percent for the placebo arm versus 72 percent in the Avastin arm (p=0.052).
• Adverse events (Grade 3-5) of special interest occurred in 28.7 percent of patients in the Avastin arm compared to 15.2 percent of patients in the radiation and chemotherapy plus placebo arm. Adverse events (Grade 3-5) of special interest that occurred more often (>2 percent increased incidence) in the Avastin arm compared to the control arm were high blood pressure (10.3 percent vs. 2.0 percent) and too much protein in the urine (proteinuria; 3.7 percent vs. 0 percent).