FDA Approves Genentech’s Avastin® (Bevacizumab) Plus Chemotherapy for a Specific Type of Advanced Ovarian Cancer

– Approval based on two large Phase III studies including GOG-0213
that showed a five month overall survival difference for women with
platinum-sensitive recurrent ovarian cancer on Avastin plus chemotherapy
compared to chemotherapy alone

– In the United States, Avastin is now approved for nine distinct
uses across six different types of cancer –

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),
today announced that the U.S. Food and Drug Administration (FDA) has
approved Avastin® (bevacizumab), either in combination with
carboplatin and paclitaxel or in combination with carboplatin and
gemcitabine chemotherapy, followed by Avastin alone, for the treatment
of patients with platinum-sensitive recurrent epithelial ovarian,
fallopian tube or primary peritoneal cancer. Women are said to have a
‘platinum-sensitive’ form of the disease if a relapse occurs six months
or longer following the last treatment with a platinum-based
chemotherapy.

“With today’s approval of Avastin plus chemotherapy, women in the U.S.
with recurrent, platinum-sensitive ovarian cancer now have a treatment
option that showed a survival difference of more than five months
compared to chemotherapy alone in a clinical trial,” said Sandra
Horning, M.D., chief medical officer and head of Global Product
Development. “This approval was based in part on a Gynecologic Oncology
Group cooperative clinical trial and reinforces the importance of
partnerships with study groups to identify new treatment options for
people in need.”

“In the United States, ovarian cancer causes more deaths annually than
any other gynecologic cancer,” said David Barley, chief executive
officer, National Ovarian Cancer Coalition (NOCC). “This approval
demonstrates Genentech’s commitment to women with ovarian cancer, a
disease with signs and symptoms that too often go unrecognized.”

Avastin in combination with chemotherapy for platinum-sensitive
recurrent epithelial ovarian, fallopian tube or primary peritoneal
cancer was granted priority review, and today’s approval is based on
results from two randomized, controlled Phase III studies, GOG-0213 and
OCEANS. The GOG-0213 study demonstrated that adding Avastin to
chemotherapy showed an overall survival difference of five months
compared to chemotherapy alone (median OS: 42.6 months vs. 37.3 months;
Hazard Ratio (HR)=0.84, 95% CI: 0.69-1.01 and HR=0.82, 95% CI:
0.68-0.996, depending on stratification factor*). Both the GOG-0213 and
OCEANS studies demonstrated a significant improvement in the time women
lived without their disease getting worse (progression-free survival,
PFS). The GOG-0213 study showed that women lived a median of 3.4 months
longer without disease progression with the addition of Avastin to
chemotherapy compared to chemotherapy alone (median PFS: 13.8 months vs.
10.4 months; HR=0.61, 95% CI: 0.51-0.72). The OCEANS study showed that
Avastin in combination with chemotherapy significantly improved PFS
compared to placebo plus chemotherapy (median PFS: 12.4 months vs. 8.4
months; HR=0.46, 95% CI: 0.37-0.58; p<0.0001). Overall survival, one of
the secondary endpoints in the OCEANS study, was not significantly
improved with the addition of Avastin to chemotherapy (HR=0.95, 95% CI:
0.77-1.17). Adverse events in both studies were consistent with those
seen in previous trials of Avastin across tumor types for approved
indications, but also included fatigue, low white blood cell count with
fever, low sodium level in the blood, pain in extremity, low platelet
count, too much protein in the urine, high blood pressure and headache. (*refer
to details under GOG-0213 data table)

In November 2014, Avastin was approved in the United States for the
treatment of women with platinum-resistant recurrent epithelial ovarian,
fallopian tube or primary peritoneal cancer in combination with
paclitaxel, pegylated liposomal doxorubicin or topotecan chemotherapy.
Women are considered to have a ‘platinum-resistant’ form of the disease
if a relapse occurs less than six months after the last treatment with a
platinum-based chemotherapy.

About the GOG-0213 and OCEANS Studies

GOG-0213 is an independent Phase III study sponsored by the National
Cancer Institute (NCI) and conducted by the Gynecologic Oncology Group
(GOG) that enrolled 673 women with platinum-sensitive recurrent
epithelial ovarian, fallopian tube or primary peritoneal cancer. The
primary endpoint of the study was to assess whether the addition of
Avastin to chemotherapy (carboplatin and paclitaxel) followed by
continued use of Avastin alone increased overall survival (OS) compared
to chemotherapy alone. Progression-free survival (PFS) and objective
response rate (ORR) were secondary endpoints in the GOG-0213 study.

 
GOG-0213 Study Results
Treatment Arm  

Avastin +
chemotherapy
(n=337)

 

Chemotherapy alone
(n=336)

Primary Endpoint: Overall Survival (OS)
Median OS   42.6 months   37.3 months
Hazard Ratio (95% CI) (IVRS)1   0.84 (0.69, 1.01)
Hazard Ratio (95% CI) (eCRF)2   0.82 (0.68, 0.996)
Secondary Endpoint: Progression-Free Survival (PFS)
Median PFS   13.8 months   10.4 months
Hazard Ratio (95% CI)   0.61 (0.51, 0.72)
Secondary Endpoint: Objective Response Rate (ORR)
ORR %   78%   56%

Number of patients with
measurable disease at
baseline

  274   286
Safety Profile
Grade 3 or 4 adverse events occurring at a higher incidence (≥2%)
in 325 patients treated with Avastin plus chemotherapy compared to
332 patients treated with chemotherapy alone were hypertension
(11.1% vs. 0.6%), fatigue (7.7% vs. 2.7%), febrile neutropenia (6.2%
vs. 2.7%), proteinuria (8.0% vs. 0.0%), abdominal pain (5.8% vs.
0.9%), hyponatremia (3.7% vs. 0.9%), headache (3.1% vs. 0.9%) and
pain in extremity (3.4% vs. 0.0%). No Grade ≥ 3 adverse events
occurred with a ≥ 2% higher frequency in the chemotherapy alone arm
compared to the Avastin plus chemotherapy arm. There were no Grade 5
adverse events occurring at a higher incidence (≥ 2%) in the Avastin
plus chemotherapy arm compared to the chemotherapy alone arm.

1 Hazard ratio was estimated from Cox proportional hazards
models stratified by the duration of treatment free-interval prior to
enrolling onto this study per IVRS (interactive voice response system)
and secondary surgical debulking status.

2 Hazard ratio was estimated from Cox proportional hazards
models stratified by the duration of platinum free-interval prior to
enrolling onto this study per eCRF (electronic case report form) and
secondary surgical debulking status.

OCEANS, a company sponsored trial, is a placebo-controlled, randomized,
multicenter Phase III study that evaluated the safety and efficacy of
Avastin, administered in combination with chemotherapy (carboplatin and
gemcitabine), in 484 women with platinum-sensitive recurrent epithelial
ovarian, fallopian tube or primary peritoneal cancer. The primary
endpoint of the study was PFS, as determined by the investigator using
Response Evaluation Criteria for Solid Tumors (RECIST). Secondary
endpoints included ORR, OS and safety.

 
AVF4095g (OCEANS) Study Results
Treatment Arm

Avastin + chemotherapy
(n=242)

 

Placebo + chemotherapy
(n=242)

 

Primary Endpoint: Progression-Free Survival (PFS)
Median PFS 12.4 months 8.4 months
Hazard Ratio (95% CI) p-value 0.46 (0.37, 0.58)

<0.0001

Secondary Endpoint: Objective Response Rate (ORR)
ORR % 78% 57%
p-value <0.0001
Safety Profile
Grade 3 or 4 adverse events occurring at a higher incidence (≥ 2%)
in 247 patients treated with Avastin plus chemotherapy compared to
233 patients treated with placebo plus chemotherapy were
thrombocytopenia (40.1% vs. 33.9%), nausea (4.5% vs. 1.3%), fatigue
(6.5% vs. 4.3%), headache (3.6% vs. 0.9%), proteinuria (9.7% vs.
0.4%), dyspnea (4.5% vs. 1.7%), epistaxis (4.9% vs. 0.4%) and
hypertension (17.0% vs. 0.9%). Grade ≥ 3 anemia (16.2% vs. 18.9%)
and decreased white blood cell count (1.6% vs. 4.3%) occurred with a
≥ 2% higher frequency in the chemotherapy alone arm compared to the
Avastin plus chemotherapy arm. There were no Grade 5 adverse events
occurring at a higher incidence (≥ 2%) for the Avastin plus
chemotherapy arm compared to the placebo plus chemotherapy arm.
 

About Ovarian Cancer

Ovarian cancer causes more deaths than any other gynecologic cancer in
the United States. In 2016, about 22,200 women will be diagnosed with
ovarian cancer in the United States and about 14,200 will die from the
disease. Patients are said to have ‘platinum-sensitive’ disease if a
relapse occurs six months or longer following the last cycle of
platinum-based chemotherapy. About half of those who relapse after
initial treatment – over 8,000 women – will have platinum-sensitive
ovarian cancer.

About Genentech Access Solutions

Access Solutions is part of Genentech’s commitment to helping people
access the Genentech medicines they are prescribed, regardless of their
ability to pay. The team of in-house specialists at Access Solutions is
dedicated to helping people navigate the access and reimbursement
process, and to providing assistance to eligible patients in the United
States who are uninsured or cannot afford the out-of-pocket costs for
their medicine. To date, the team has helped more than 1.4 million
patients access the medicines they need. Please contact Access Solutions
(866) 4ACCESS/(866) 422-2377 or visit http://www.Genentech-Access.com
for more information.

About Avastin

Avastin is a prescription-only medicine that is a solution for
intravenous infusion. It is a biologic antibody designed to specifically
bind to a protein called vascular endothelial growth factor (VEGF) that
plays an important role throughout the lifecycle of the tumor to develop
and maintain blood vessels, a process known as angiogenesis. Avastin is
designed to interfere with the tumor blood supply by directly binding to
the VEGF protein to prevent interactions with receptors on blood vessel
cells. The tumor blood supply is thought to be critical to a tumor’s
ability to grow and spread in the body (metastasize).

Avastin Indications:

  • Avastin is indicated for the first or second line treatment of
    patients with metastatic colorectal cancer in combination with
    intravenous 5 fluorouracil–based chemotherapy.
  • Avastin in combination with fluoropyrimidine-irinotecan or
    fluoropyrimidine-oxaliplatin based chemotherapy is indicated for the
    second line treatment of patients with metastatic colorectal cancer
    who have progressed on a first line Avastin-containing regimen.
    Avastin is not indicated for adjuvant treatment of colon cancer.
  • Avastin in combination with carboplatin and paclitaxel chemotherapy is
    indicated for first line treatment of patients with unresectable,
    locally advanced, recurrent or metastatic nonsquamous, non-small cell
    lung cancer.
  • Avastin is indicated for the treatment of metastatic renal cell
    carcinoma in combination with interferon alfa.
  • Avastin in combination with paclitaxel and cisplatin or paclitaxel and
    topotecan is indicated for the treatment of persistent, recurrent or
    metastatic carcinoma of the cervix.
  • Avastin in combination with paclitaxel, pegylated liposomal
    doxorubicin or topotecan, is approved to treat platinum-resistant
    recurrent epithelial ovarian, fallopian tube or primary peritoneal
    cancer (prOC) in women who received no more than
    two prior chemotherapy treatments. Avastin, either in combination with
    carboplatin and paclitaxel or with carboplatin and gemcitabine,
    followed by Avastin alone, is approved for the treatment of patients
    with platinum-sensitive recurrent epithelial ovarian, fallopian tube
    or primary peritoneal cancer (psOC).

BOXED WARNINGS and Additional Important Safety Information

People receiving Avastin may experience side effects. In clinical
trials, some people treated with Avastin experienced serious and
sometimes fatal 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 event occurred in more people who received
    Avastin than in the comparison group (up to 3.2%).
  • In some cases, GI perforation resulted in fatality. Avastin therapy
    should be permanently stopped if GI perforation occurs.

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.
  • Surgery and wound healing problems occurred more often in people who
    received Avastin than in the comparison group. In a controlled
    clinical trial, in patients with metastatic colorectal cancer who had
    surgery during the course of treatment, the incidence of wound healing
    complications, including serious and fatal complications, was 15% for
    patients who received Avastin and 4% for patients who did not receive
    Avastin.
  • Avastin therapy should not be started for at least 28 days after
    surgery and until the surgical wound is fully healed. The length of
    time between stopping Avastin and having voluntary surgery without the
    risk of wound healing problems following surgery has not been
    determined.
  • Treatment with Avastin should be stopped at least 28 days before
    voluntary surgery and in people with wound healing problems following
    surgery that require medical treatment. Treatment with Avastin should
    be stopped in patients with slow or incomplete wound healing.

Severe bleeding:

  • Treatment with Avastin can result in serious or fatal bleeding,
    including coughing up blood, bleeding in the stomach, vomiting of
    blood, bleeding in the brain, nosebleeds and vaginal bleeding. These
    events occurred up to five times more often in people who received
    Avastin compared to patients who received only chemotherapy.
  • Across cancer types, 0.4% to 6.9% of people who received Avastin
    experienced severe to fatal bleeding. People who have recently coughed
    up blood (greater than or equal to a half teaspoon of red blood) or
    have serious bleeding should not receive Avastin. Treatment with
    Avastin should be permanently stopped if serious bleeding occurs.

Additional serious adverse events

In clinical trials for different cancer types, there were additional
serious and sometimes fatal side effects that occurred in more people
who received Avastin than in those in the comparison group.

  • The formation of an abnormal passage in the body (GI and non-GI
    fistula formation) was seen in up to 2% of people in metastatic
    colorectal cancer and ovarian cancer patients. In a study of patients
    with cervical cancer, formation of an abnormal passage between the
    vagina and GI tract was seen in 8.3% of people.
  • Severe to life-threatening stroke or heart problems were seen in 2.6%
    of people.
  • Too much protein in the urine that led to kidney problems was seen in
    ≤1% of people.
  • Additional serious side effects that occurred in more people who
    received Avastin than those in the comparison group included

    • Severe to life-threatening blood clots (VTE), up to 10.6%
    • Severe to life-threatening high blood pressure, which was seen in
      5% to 18% of people
    • Nervous system and vision disturbances (Posterior Reversible
      Encephalopathy Syndrome), which was seen in less than 0.5% of
      people.
    • Infusion reactions with the first dose of Avastin were uncommon
      and occurred in less than 3% of people, and severe reactions
      occurred in 0.2% of people.
  • Avastin could cause a woman’s ovaries to stop working and may impair
    her ability to have children. Avastin should not be used in ovarian
    cancer patients who have evidence of recto-sigmoid involvement by
    pelvic examination or bowel involvement on CT scan or clinical
    symptoms of bowel obstruction.

Patients who are pregnant, think they are pregnant, or thinking of
becoming pregnant should talk with their doctor about the potential risk
of loss of the pregnancy or the potential risk of Avastin to the fetus
during and following Avastin therapy, and the need to continue an
effective birth control method for six months following the last dose of
Avastin. Avastin can cause fertility issues for women.

Women should be advised that breastfeeding while on Avastin may harm the
baby and is therefore not recommended.

Common side effects that occurred in more than 10% of people who
received Avastin for different cancer types, and at least twice the rate
of the comparison group, were nosebleeds, headache, high blood pressure,
inflammation of the nose, too much protein in the urine, taste change,
dry skin, rectal bleeding, tear production disorder, back pain and
inflammation of the skin (exfoliative dermatitis).

Across all trials, treatment with Avastin was permanently stopped in
8.4% to 21% of people because of side effects.

Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch.
Report side effects to Genentech at (888) 835-2555.

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

About Genentech

Founded 40 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 member of the Roche Group, has headquarters in South San
Francisco, California. For additional information about the company,
please visit http://www.gene.com.

Contacts

Genentech
Media Contact:
Andrew Villani, 650-467-6800
Advocacy
Contact:
Chris Campbell, 650-467-8466
Investor Contacts:
Neera
Dahiya Ravindran, M.D., 650-491-5281
Karl Mahler, Ph.D., 011 41 61
687 8503

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