Genentech halts Avastin drug study
platinum-refractory ovarian cancer patients have been discontinued
due to patients developing a serious bowel problem.
The news is a big blow for Genentech, who had hailed the drug as the jewel in its developmental pipeline. Initially licensed for colon cancer, it has become the first success story for attacking tumours by starving their blood supply.
It is the only drug currently on the market that does this, and many doctors have been using it "off label" against a variety of cancer types, such as lung and breast tumours.
Enrollment for the latest round of studies was halted after reports of five GI perforations observed in the first 44 patients enrolled in the proposed 53-patient study.
"GI perforations are a known possible adverse event with Avastin; however, we chose to discontinue enrollment in this Phase II study due to the observation of a higher rate seen in this study than in other trials of Avastin in ovarian cancer or other tumour types," said Hal Barron, Genentech's senior vice president, development, and chief medical officer.
"We are continuing our plans to study Avastin in ovarian cancer based on the activity seen to date and the significant unmet medical need in this patient population, and currently do not expect these results to affect our plans to study Avastin in earlier-stage ovarian cancer or other tumour types," he added.
Avastin is a therapeutic antibody designed to inhibit Vascular Endothelial Growth Factor (VEGF), a protein that plays an important role in tumour angiogenesis and maintenance of existing tumour vessels.
By binding to VEGF, Avastin is designed to interfere with the blood supply to tumours, a process that is critical to tumour growth and metastasis. The FDA approved Avastin on February 26, 2004 as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy.
Genentech said in a statement that the decision to discontinue enrollment was made by Genentech in consultation with the FDA. Study investigators are being notified today so they can have informed conversations with their patients.
"The limited overall number of GI perforations seen in this study prevent us from ascertaining definitive risk factors for this adverse event," said Barron.
"Patients enrolled in this study had more advanced disease, which typically involves the bowel, and had received more prior chemotherapy than in previous clinical trials of Avastin in ovarian cancer."
Avastin may have become the victim of its own success. Having been hailed the best drug since Taxol for ovarian cancer, the problem could lie in the drug's ability to kill tumour cells that have replaced healthy bowel tissue, leading to a dead area that then perforates.
None of the other "targeted" drugs like ImClone Systems' Erbitux, AstraZeneca's Iressa or Genentech's Tarceva work the same way, and should not share the problem.
Avastin sales in the United States increased 85 per cent to $245.7 million (€204.3 million) for the quarter ended June 30, from $133 million in the same period a year ago.
