Wednesday, Oct 25, 2017

FDA Accepts Genentech’s Supplemental Biologics License Application for Avastin as a Front-Line Treatment for Women with Advanced Ovarian Cancer

South San Francisco, CA -- October 25, 2017 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) has accepted the company's supplemental Biologics License Application (sBLA) for Avastin^® (bevacizumab) in combination with chemotherapy (carboplatin and paclitaxel), followed by Avastin alone, for the front-line treatment of women with advanced ovarian cancer.

“About 80 percent of women with ovarian cancer are diagnosed in the advanced stages when the disease is difficult to treat and options are limited,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are committed to working closely with the FDA to bring this potential new treatment option to women with newly diagnosed advanced ovarian cancer as soon as possible.”

This sBLA for Avastin, in combination with carboplatin and paclitaxel, followed by Avastin as a single agent, for the front-line treatment of people with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, is based on data from the pivotal Phase III GOG-0218 trial. In newly diagnosed advanced ovarian cancer, the first treatment a woman receives after surgery is known as front-line treatment. The FDA is expected to make a decision on approval by June 25, 2018.

This is part of our broader development program for Avastin in ovarian cancer. Avastin is currently approved for treating two different forms of advanced disease that recurred after platinum-based chemotherapy. In addition, Genentech is evaluating Avastin in combination with Tecentriq ^® (atezolizumab) and chemotherapy for the treatment of newly diagnosed advanced ovarian cancer in the Phase III IMagyn050 trial (NCT03038100).

About the GOG-0218 Study

GOG-0218 (NCT00262847) is a multi-center, randomized, double-blind, placebo-controlled Phase III study in 1,873 women with previously untreated advanced epithelial ovarian, primary peritoneal, or fallopian tube carcinoma who already had surgery to remove as much of the tumor as possible. Participants were randomized into one of three treatment arms: chemotherapy alone (carboplatin and paclitaxel), Avastin (15 mg/kg) plus chemotherapy followed by placebo alone, or Avastin plus chemotherapy followed by Avastin alone. Women who received Avastin in combination with chemotherapy, and continued use of Avastin alone for a total duration of 22 cycles, had a median progression-free survival (PFS) of 18.2 months compared to 12.0 months in women who received chemotherapy alone (HR=0.64; 95% CI 0.54 - 0.77, p<0.0001). Secondary endpoints of the study included overall survival (OS) and objective response rate (ORR). Adverse events were consistent with those seen in previous trials of Avastin across tumor types for approved indications. The study was conducted by the Gynecologic Oncology Group (GOG) and their initial results were previously published in the New England Journal of Medicine.

About Ovarian Cancer

Ovarian cancer causes more deaths among women than any other gynecologic cancer in the United States. In 2017, nearly 22,000 women will be diagnosed with ovarian cancer in the U.S. and more than 14,000 will die from the disease. About 80% of ovarian cancer cases are found at an advanced stage, when the cancer has spread beyond the ovaries. Early ovarian cancer often does not have any symptoms and when symptoms, such as abdominal swelling, bloating, abdominal pain, difficulty eating or feeling full quickly, and/or frequent urination, are present, they can be associated with other less serious conditions. Five-year survival rates worsen dramatically based on stage of diagnosis.

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 more than 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.

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