FDA Grants Accelerated Approval of Avastin for Brain Cancer (Glioblastoma) That Has Progressed Following Prior Therapy

SOUTH SAN FRANCISCO, Calif.--(Business Wire)--
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 AVF3708g

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).

About Avastin

Avastin is a biologic antibody designed to specifically inhibit the vascular
endothelial growth factor (VEGF) protein that plays an important role in the
development and maintenance of blood vessels, a process known as angiogenesis.
Glioblastomas express high levels of VEGF and develop an extensive network of
tumor blood vessels. VEGF is a potent activator of angiogenesis throughout the
lifecycle of a tumor and is thought to be critical to a tumor's ability to grow
and spread in the body (metastasize).

Avastin was the first anti-angiogenesis therapy approved by the FDA and is now
approved for the treatment of four tumor types. In addition to glioblastoma that
has progressed following prior therapy, Avastin is also indicated for the first-
and second-line treatment of metastatic colorectal cancer (mCRC) in combination
with intravenous 5-FU-based chemotherapy; 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; and for
previously untreated, metastatic or locally recurrent HER2-negative breast
cancer in combination with paclitaxel. The effectiveness of Avastin in
metastatic breast cancer is based on an improvement in progression-free
survival. Avastin is not indicated for patients with breast cancer that has
progressed following anthracycline and taxane chemotherapy administered for
metastatic disease. Currently, no data are available that demonstrate an
improvement in disease-related symptoms or increased survival with Avastin in
breast cancer.

BOXED WARNINGS and Additional Important Safety Information

Patients treated with Avastin may experience side effects. In clinical trials,
some patients treated with Avastin experienced serious side effects, including:

Gastrointestinal (GI) perforation:

Treatment with Avastin can result in the development of a serious side effect
called GI perforation, which is the development of a hole in the stomach, small
intestine, or large intestine. In clinical trials, this side effect occurred in
0.3 to 2.4 percent of patients and in some cases resulted in fatality. Avastin
therapy should be permanently stopped in people with GI perforation.

Surgery and wound healing problems:

Treatment with Avastin can lead to slow or incomplete wound healing (for
example, when a surgical incision has trouble healing or staying closed). In
some cases this event resulted in fatality. In a clinical trial, 15 percent of
patients with metastatic colorectal cancer who had surgery while receiving
Avastin treatment had serious and fatal complications. Avastin should not be
initiated for at least 28 days following surgery and until the surgical wound is
fully healed. Avastin therapy should be permanently stopped in patients with
wound healing problems that require medical treatment. The appropriate waiting
time between stopping treatment with Avastin and having surgery has not been
determined.

Severe bleeding:

Severe or fatal bleeding, including hemoptysis (coughing up of blood), GI
bleeding, hematemesis (bloody vomit), central nervous system (CNS) hemorrhage
(bleeding in the brain), epistaxis (nose bleeds), and vaginal bleeding has
occurred up to five-fold more frequently in patients receiving Avastin. Grade 3
or higher (severe or fatal) bleeding events have occurred in 1.2 to 4.6 percent
of patients receiving Avastin. In patients with previously treated glioblastoma,
intracranial hemorrhage (bleeding within the brain) occurred in eight of 163
patients and two people had Grade 3 to 4 (severe) bleeding. Some people
receiving Avastin with chemotherapy for lung cancer experienced hemoptysis. In
some cases, this event resulted in fatality. People with serious bleeding or
recent hemoptysis should not receive Avastin.

In clinical trials, additional serious side effects seen across different cancer
types, in some cases resulting in fatality, included the following: formation of
an abnormal passage from parts of the body to another part (non-GI fistula
formation - less than 0.3 percent), stroke or heart problems (arterial
thromboembolic events - 2.6 percent), high blood pressure (5 to 18 percent),
nervous system and vision disturbances known as reversible posterior
leukoencephalopathy syndrome or RPLS (less than 0.1 percent), severe infusion
reactions (0.2 percent), and too much protein in the urine (that may be a sign
of kidney problems) was increased.

The most common adverse reactions observed in Avastin patients at a rate of more
than 10 percent and at least twice the control arm rate were nose bleeds,
headache, high blood pressure, irritation of the nose (rhinitis), protein in the
urine, taste alteration, dry skin, rectal bleeding, tear production disorder
(lacrimation), and inflammation of the skin (exfoliative dermatitis).

Avastin may cause problems getting pregnant. Women who are pregnant or thinking
of becoming pregnant should talk with their doctor about the potential risks of
loss of pregnancy or the potential risk of Avastin to the fetus. Nursing mothers
should not breast-feed while receiving Avastin or for a short period of time
after treatment is finished.

For full Prescribing Information and Boxed WARNINGS on Avastin visit
http://www.avastin.com.

About Genentech Access Solutions

Genentech is committed to people having access to our medicines. Genentech
Access Solutions is a team of 350 Genentech employees who help those who need
Genentech medicines. This team works with patients and doctors to resolve
reimbursement and insurance issues and provides assistance to eligible patients
in the United States who do not have insurance coverage or who cannot afford
their out-of-pocket co-pay costs.

Since its first medicine was approved in 1985, Genentech has donated
approximately $1.3 billion in free Genentech medicine to the uninsured through
the Genentech® Access to Care Foundation (GATCF) and other product donation
programs. The household income limit to receive free medicine through GATCF is
$100,000 per year. Since 2005, Genentech has also donated approximately $250
million to various independent, non-profit organizations that provide financial
assistance to those who cannot access needed medical treatment due to co-pay
costs.

About Genentech

Founded more than 30 years ago, Genentech is a leading biotechnology company
that discovers, develops, manufactures and commercializes medicines to treat
patients with serious or life-threatening medical conditions. The company, a
wholly-owned member of the Roche Group, has headquarters in South San Francisco,
California. For additional information about the company, please visit
http://www.gene.com.

Genentech, Inc.
Media:
Charlotte Arnold, 650-467-6800
or
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Kathee Littrell, 650-225-1034
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or
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