Monday, Nov 3, 2008
South San Francisco, Calif. -- November 3, 2008 --Genentech, Inc. (NYSE: DNA) today announced that the company submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for Avastin® (bevacizumab) as a therapy for people with previously treated glioblastoma. If accepted by the FDA, the application would be considered for an accelerated approval that allows provisional approval of medicines for cancer or other life-threatening diseases based on preliminary evidence suggesting clinical benefit.
Glioblastoma is the most aggressive type of brain cancer with no cure and few treatment options. Following initial treatment with chemotherapy and radiation, more than 90 percent of people with glioblastoma will see their cancer return and there are few effective treatments when the initial therapy stops working.
The Avastin application is based on a Phase II clinical trial (BRAIN) in previously treated glioblastoma that evaluated Avastin as a single agent or in combination with irinotecan chemotherapy. When Avastin was evaluated as a single agent, the study showed that at six months 43 percent of patients lived without their disease advancing, as defined by progression-free survival (PFS). In the study, 28 percent of patients responded to Avastin, meaning tumors decreased in size by at least 50 percent. Patients receiving Avastin had a median overall survival of 9.3 months, a secondary endpoint in the study. Most adverse events related to Avastin in this trial appeared to be similar to those previously reported in other Avastin studies. The most common severe (Grade 3 or greater) toxicities in the Avastin-only arm were hypertension (8 percent) and convulsion (6 percent). There were two deaths associated with adverse events in the Avastin-only arm. These data, along with those from the combined Avastin and irinotecan study arm, were presented earlier this year at the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO).
"There has been no substantial improvement in the treatment of glioblastoma in more than 20 years. This is a devastating disease and people with glioblastoma desperately need new treatment options," said Hal Barron, M.D., senior vice president of development and chief medical officer. "We look forward to working with the FDA to potentially make Avastin the first targeted therapy to be approved for the treatment of previously treated glioblastoma."
Genentech plans to initiate a global Phase III study in patients with newly diagnosed glioblastoma in the first half of 2009 that will evaluate Avastin with standard of care chemotherapy and radiation.
According to the National Cancer Institute there are about 19,000 cases of primary brain tumors - those that originate in the brain - diagnosed every year in the U.S. Glioblastoma is the most common type of brain tumor. According to historical estimates, the median survival of patients with previously treated glioblastoma is typically three to six months. Currently, only 15 percent of patients usually live six months without their cancer advancing and fewer than ten percent of patients respond to treatment. Glioblastoma is particularly devastating for people because tumors can invade brain tissue impairing the areas responsible for thinking, personality, movement and other essential body functions.
Glioblastoma is associated with high concentrations of vascular endothelial growth factor (VEGF), a protein associated with tumor growth and spread. Preclinical studies have shown a correlation between a high concentration of VEGF and a poorer prognosis in glioblastoma.
About the BRAIN Study
The Phase II, open-label, multicenter, randomized, non-comparative study enrolled 167 patients with glioblastoma whose cancer had relapsed after first- or second-line therapy. All patients had received prior temozolomide and radiation. Patients were randomized to receive Avastin alone or in combination with irinotecan every other week for up to 104 weeks. The primary endpoints were six-month PFS and objective response rate as determined by an independent review of patient scans. Objective response rate was defined as a decrease in tumor size by at least 50 percent on two consecutive assessments at least four weeks apart. PFS was defined as the absence of any event of cancer progression or death. Secondary endpoints of the study included overall survival and safety.
Avastin is a biologic antibody designed to specifically inhibit the VEGF protein that plays an important role in the development and maintenance of blood vessels, a process known as angiogenesis. VEGF is a potent activator of angiogenesis throughout the lifecycle of a tumor. By inhibiting VEGF Avastin is designed to interfere with the blood supply to a tumor, which is thought to be critical to a tumor's ability to grow and spread in the body (metastasize). For more information on angiogenesis, visit http://www.gene.com.
Avastin is indicated for the first- and second-line treatment of metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy and 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.
The most serious side effects associated with Avastin across all trials were gastrointestinal (GI) perforation, slow wound healing, severe bleeding, formation of an abnormal passage from parts of the body to another part, blood clots, severe high blood pressure, nervous system and vision disturbances, reduced white blood cell counts, kidney malfunction, and congestive heart failure.
The most common serious adverse events across different cancer types were high blood pressure, blood clots, stroke, reduced white blood cell counts, infection, bleeding, weakness, abdominal pain, pain, headache, tiredness, a brief loss of consciousness, diarrhea, constipation, blockage of the bowel, nausea, vomiting, dehydration, numbness and tingling in fingers and toes, and too much protein in the urine. For full Prescribing Information and Boxed Warnings on Avastin, visit http://www.avastin.com.
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines for patients with significant unmet medical needs. The company has headquarters in South San Francisco, California and is listed on the New York Stock Exchange under the symbol DNA. For additional information about the company, please visit http://www.gene.com.
This press release contains forward-looking statements regarding a potential approval for Avastin and initiating clinical studies of Avastin. These forward-looking statements are predictions and involve risks and uncertainties that could cause actual results to differ materially from those predicted in any such forward-looking statements. Such risks and uncertainties include, but are not limited to, difficulty in enrolling patients in clinical trials; the need for additional data, data analysis or clinical studies; the results of clinical trials; FDA actions or delays; unexpected safety, efficacy or manufacturing issues for Genentech or our contract/collaborator manufacturers; product withdrawals; and our ability to protect our proprietary rights. Please also refer to the risk factors identified in Genentech's periodic reports filed with the Securities and Exchange Commission. Genentech disclaims and does not undertake any obligation to update or revise any forward-looking statement in this press release.