Genentech, Inc. announced that the company submitted a supplemental Biologics License Application (sBLA) to the US 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 per cent of patients lived without their disease advancing, as defined by progression-free survival (PFS). In the study, 28 per cent of patients responded to Avastin, meaning tumours decreased in size by at least 50 per cent. 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 per cent) and convulsion (6 per cent). 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 tumours - those that originate in the brain - diagnosed every year in the US. Glioblastoma is the most common type of brain tumour. According to historical estimates, the median survival of patients with previously treated glioblastoma is typically three to six months. Currently, only 15 per cent 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 tumours 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 tumour growth and spread. Preclinical studies have shown a correlation between a high concentration of VEGF and a poorer prognosis in glioblastoma.
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 tumour. By inhibiting VEGF Avastin is designed to interfere with the blood supply to a tumour, which is thought to be critical to a tumour's ability to grow and spread in the body (metastasize).
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.
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.