Genentech and Roche in positive Avastin result

A Phase II study, initiated by Genentech and Roche, of the investigational drug Avastin (bevacizumab) plus 5-FU/Leucovorin chemotherapy in 209 previously-untreated metastatic colorectal cancer patients showed a 29% improvement in median survival, the primary endpoint, which did not achieve statistical significance.

The study also showed a 67% prolongation in median progression-free survival, which was highly statistically significant, in patients treated with Avastin plus 5-FU/Leucovorin compared with 5-FU/Leucovorin alone.

'We're encouraged that a survival trend was observed and that patients also experienced a statistically significant improvement in progression-free survival, which is clinically meaningful for patients with metastatic cancer and consistent with the results of our Phase III trial,' said Dr Susan Hellmann, Genentech's executive vice president, development and product operations, and chief medical officer. 'We filed the Biologics License Application for Avastin in September, and we continue to expect FDA approval no later than the end of the first quarter of 2004.'

This randomised, controlled, multi-centre study enrolled patients who were not optimal candidates to receive first-line CPT-11. In this Phase II study, the addition of Avastin to 5-FU/Leucovorin was well tolerated and the safety profile was consistent with that seen in previous Avastin clinical trials in colorectal cancer. Only Grade 3 hypertension, easily managed with oral medications, and asymptomatic proteinuria were increased in this trial. As in the pivotal Phase III study, although uncommon, the incidence of gastrointestinal perforation may be increased by the addition of Avastin to chemotherapy (two cases, 2%).

Results of the 900-patient pivotal study of Avastin plus the IFL chemotherapy regimen (5-FU/Leucovorin/CPT-11) were announced earlier this year and showed that Avastin plus the IFL regimen improved median survival by approximately five months, compared with patients treated with chemotherapy alone (20.3 months versus 15.6 months). These data were the basis for the Biologics License Application (BLA) for Avastin in metastatic colorectal cancer, which was submitted to the U.S. Food and Drug Administration (FDA) in September.

About VEGF and Tumour Angiogenesis

The link between angiogenesis and cancer growth has been discussed by many researchers for decades, but it wasn't until 1989 that a key growth factor influencing the process, Vascular Endothelial Growth Factor (VEGF), was discovered by Dr Napoleone Ferrara, a staff scientist at Genentech. Dr Ferrara and his team cloned VEGF, providing some of the first evidence that a specific angiogenic growth factor existed. This research was published in the journal Science in 1989. Dr. Ferrara then created a mouse antibody to this protein. In 1993, Dr. Ferrara and his team at Genentech, in a study published in Nature, demonstrated that the antibody directed against VEGF could suppress angiogenesis and tumor growth in preclinical models, providing compelling evidence that VEGF can play a critical role in tumor growth. Clinical studies with a humanized version of the antibody, Avastin, began in 1997.

About Avastin

Avastin is an investigational therapeutic antibody designed to inhibit VEGF, a protein that plays an important role in tumor angiogenesis and maintenance of existing tumor vessels. By inhibiting VEGF, Avastin is designed to interfere with the blood supply to tumors, a process that is critical to tumor growth and metastasis. Based on preclinical and clinical studies showing that VEGF plays a broad role in a range of cancers, Genentech is pursuing a late-stage clinical development program with Avastin evaluating its potential use in metastatic colorectal, renal cell (kidney), breast and non-small cell lung cancers. Avastin is also being evaluated in earlier stage trials as a potential therapy in pancreatic, prostate, ovarian, melanoma and several types of solid tumor cancers and hematologic malignancies. To date, more than 2,000 patients have been treated with Avastin in clinical studies.

About Colorectal Cancer

According to the American Cancer Society, colorectal cancer is the second leading cause of cancer death in the United States and the third most frequently diagnosed cancer. The American Cancer Society estimates that 147,500 new cases of colorectal cancer will be diagnosed in the United States in 2003.