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FDA Grants Accelerated Approval of Bevacizumab for Glioblastoma

South San Francisco, Calif. -- May 5, 2009 -- Genentech, Inc. announced today that the U.S. Food and Drug Administration (FDA) granted accelerated approval of Avastin® (bevacizumab) for people with glioblastoma with progressive disease following prior therapy. The effectiveness of Avastin in this aggressive form of brain cancer is based on an improvement in objective response rate. Currently, no data are available from randomized controlled trials demonstrating an improvement in disease-related symptoms or increased survival with Avastin in glioblastoma.

The new indication for Avastin was granted under the FDA's accelerated approval program that allows provisional approval of medicines for cancer or other life-threatening diseases.

"People with this type of brain cancer have had no new treatments in more than a decade," said Timothy Cloughesy, M.D., director, Neuro-Oncology Program of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles. "After so many years with little progress in this field, Avastin was associated with a durable tumor response and doctors now have a new medicine to offer patients."

"Today's approval would not have been possible without the dedication of physicians, patient advocates, the FDA and most importantly the people who participated in the clinical trials and their families who had the courage to support them," said Hal Barron, M.D., executive vice president, Global Development and chief medical officer, Genentech. "A global Phase III trial in patients with newly diagnosed glioblastoma will soon begin enrollment to further evaluate Avastin in this setting."

Glioblastoma affects approximately 10,000 people per year in the United States and glioblastoma tumors nearly always return following initial treatment.

Avastin Efficacy in Glioblastoma
Study AVF3708g
The accelerated approval is based on independently reviewed data from an open-label, multicenter, non-comparative Phase II study that included 167 patients with glioblastoma that had progressed following initial treatment with temozolomide and radiation. Patients were randomized into two arms: Avastin alone or Avastin in combination with irinotecan. A primary endpoint of the study was objective response rate. Response was assessed by magnetic resonance imaging (MRI) and measured using World Health Organization radiographic criteria along with decreased or stable corticosteroid use. MRI does not necessarily distinguish between the tumor, swelling (edema), or tissue death (necrosis) caused by prior radiation therapy.

According to an FDA analysis of the study, tumor responses were observed in 26 percent (95% confidence interval: 17.0%, 36.1%) of the 85 patients treated with Avastin alone, and the median duration of response in these patients was 4.2 months (95% confidence interval: 3.0 months, 5.7 months).

The median age of the patients treated with Avastin alone was 54 years. Additionally, 32 percent were female, 81 percent were in first relapse, 45 percent had a Karnofsky performance status (KPS) of 90 to 100 and 55 percent had a KPS of 70 to 80. Patients with active brain hemorrhage were excluded from the study.

Study NCI 06-C-0064E
The efficacy of Avastin in glioblastoma that has progressed following prior therapy is supported by another study that used the same response assessment criteria as AVF3708g. In this single-arm study, 56 patients were treated with Avastin alone. Responses were observed in 20 percent of patients (95% confidence interval: 10.9%, 31.3%), and the median duration of response was 3.9 months (95% confidence interval: 2.4 months, 17.4 months).

Avastin Safety in Glioblastoma
In study AVF3708g, safety in patients with glioblastoma that had progressed following prior therapy was consistent with Avastin experience in other tumor types.

Safety in Patients Treated with Avastin Alone in AVF3708
Avastin was discontinued due to adverse events in 5 percent of patients. The most frequently reported adverse events were infection (55 percent), fatigue (45 percent), headache (37 percent), high blood pressure (30 percent), diarrhea (21 percent) and nose bleeds (19 percent). Grade 3 or higher adverse events were infection (10 percent), high blood pressure (8 percent), fatigue (4 percent), headache (4 percent) and diarrhea (1 percent). There were two deaths possibly associated with adverse events including one retroperitoneal hemorrhage and one neutropenic infection.

Safety in All Patients in AVF3708g (Avastin Alone and Avastin Plus Irinotecan)
Avastin-related adverse events (Grades 1 to 4) across both arms of the study were bleeding/hemorrhage (40 percent), high blood pressure (32 percent), nose bleeds (26 percent), blood clots in the veins (8 percent), blood clots in the arteries (6 percent), wound-healing complications (6 percent), bleeding in the brain (5 percent), protein in the urine (4 percent), gastrointestinal (GI) perforation (2 percent), nervous system and vision disturbances known as reversible posterior leukoencephalopathy syndrome or RPLS (1 percent). Grade 3 to 5 adverse events across both arms of the study were blood clots in the veins (7 percent), high blood pressure (5 percent), blood clots in the arteries (3 percent), wound-healing complications (3 percent), GI perforation (2 percent), bleeding/hemorrhage (2 percent), bleeding in the brain (1 percent) and protein in the urine (1 percent).

Source: Genentech

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