FDA Grants Genentech’s Avastin Priority Review for Certain Types of Cervical Cancer

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has accepted the company's supplemental Biologics License Application (sBLA) and granted Priority Review for Avastin® (bevacizumab) plus chemotherapy for the treatment of women with persistent, recurrent or metastatic cervical cancer.

“This regulatory application for Avastin is important because chemotherapy is the only approved treatment for women with metastatic, recurrent or persistent cervical cancer,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Treatment with Avastin plus chemotherapy may help women with these conditions live longer than chemotherapy alone, and we look forward to working with the FDA on potentially making this medicine available to patients.”

The designation of Priority Review status is granted to medicines that the FDA believes have the potential to provide “significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.” The sBLA for Avastin plus chemotherapy in persistent, recurrent or metastatic cervical cancer is based on data from the Phase III GOG-0240 trial with an FDA action date of October 24, 2014.

About the GOG-0240 Study

GOG-0240 is an independent, National Cancer Institute (NCI)-sponsored Phase III study which assessed the efficacy and safety profile of Avastin plus chemotherapy (paclitaxel and cisplatin or paclitaxel and topotecan) in women with persistent, recurrent or metastatic cervical cancer. Study data from 452 women showed:

• The study met its primary endpoint of improving overall survival (OS) with a statistically significant 29 percent reduction in the risk of death for women who received Avastin plus chemotherapy compared to those who received chemotherapy alone (median OS: 17.0 months vs. 13.3 months; Hazard Ratio (HR)=0.71, p=0.004).
• Women in the Avastin plus chemotherapy arm also lived longer without disease worsening (progression free survival, PFS) compared to those who received chemotherapy alone (median PFS: 8.2 months vs. 5.9 months; HR=0.67, p=0.002).
• Hypertension (high blood pressure) of Grade 2 or higher was significantly more common with Avastin-containing regimens (25 percent vs. 2 percent), but no patients discontinued Avastin because of hypertension. Gastrointestinal or genitourinary fistulas (abnormal passage from one part of the body to another) of Grade 3 or higher were significantly increased with the Avastin-containing regimens (6 percent vs. 0 percent), as were thromboembolic events (blood clots) of Grade 3 or higher (8 percent vs. 1 percent).
• There was no increase in treatment-related deaths in the Avastin plus chemotherapy arm as compared to the chemotherapy alone arm.

About Cervical Cancer

It is estimated that more than 12,000 new cases of cervical cancer will be diagnosed in the United States in 2014 and about 4,000 women will die from the disease. There is a dramatic difference in survival rates between early and advanced cervical cancer. At least nine out of 10 women will live for five years following diagnosis of early stage disease but the survival rate drops to below one in six women when the disease is metastatic.

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 U.S. Indications:

Avastin is approved for first- and second-line treatment of metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy. Avastin, in combination with fluropyrimidine-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 is approved for first-line treatment of unresectable, locally advanced, recurrent or metastatic, non-squamous, non-small cell lung cancer in combination with carboplatin and paclitaxel, and metastatic renal cell carcinoma in combination with interferon alfa.

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 (2.4 percent to 0.3 percent). 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 percent for patients who received Avastin and four percent 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, 1.2 percent to 4.6 percent 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.

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 from parts of the body to another part (non-GI fistula formation) was seen in 0.3 percent or less of people. Severe to life-threatening stroke or heart problems were seen in 2.6 percent of people. Too much protein in the urine that led to kidney problems was seen in less than one percent 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 high blood pressure, which was seen in five percent to 18 percent of people, and nervous system and vision disturbances (reversible posterior leukoencephalopathy syndrome), which was seen in less than 0.1 percent of people. Infusion reactions with the first dose of Avastin were uncommon and occurred in less than three percent of people, and severe reactions occurred in 0.2 percent of people. Avastin can cause fertility issues for women. Avastin could cause a woman’s ovaries to stop working and may impair her ability to have children.

Common side effects that occurred in more than 10 percent 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 percent to 21 percent of people because of side effects.

Patients who 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 at least six months following the last dose of Avastin.

Women should be advised to discontinue nursing or discontinue treatment with Avastin, taking into account the importance of Avastin to the mother.

Report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. Patients and caregivers may also 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 35 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.