Washington Editor

Following Monday's announcement that Genentech Inc.'s Avastin biologics license application now is on file with the FDA, it's rumored that the anti-angiogenesis cancer drug proposed as a first-line therapy for metastatic colorectal cancer could enter the U.S. market within about six months.

And that's actually the conservative estimate.

Mike King, managing director with Banc of America Securities in New York, told BioWorld Today Avastin, a potential blockbuster, could win FDA approval by the end of the year and reach the market in early 2004.

"That would fit well with [FDA] commissioner Mark McClellan's public statements about wanting to approve drugs quickly," King said. "Assuming that all the paper work is in order, I think they would like to go home for the holidays in December and have this approved."

When asked about that ambitious timeline, Colleen Sweeney, Genentech's spokeswoman, told BioWorld Today the company requested a six-month priority review of the biologics license application for Avastin (bevacizumab), filed Friday, by way of the fast-track designation. If granted priority review, the Prescription Drug User Fee Act (PDUFA) action date would fall around the end of March. (Under PDUFA, the FDA is required to act on drug and biologics applications within a certain timeframe.)

Genentech's BLA is based on a pivotal Phase III trial that demonstrated a five-month, or 30 percent, extension in the median survival of patients treated with Avastin plus chemotherapy, compared to patients treated with chemotherapy alone. That is 20.3 months for the treatment arm, vs. 15.6 months for chemotherapy alone.

Avastin, a therapeutic antibody, is designed to inhibit VEGF (vascular endothelial growth factor), a protein that plays a role in tumor angiogenesis and maintenance of existing tumor vessels. By inhibiting VEGF, Avastin interferes with the blood supply to tumors and thereby affects tumor growth and metastasis, Genentech said.

King believes about 68,000 of the 150,000 U.S. residents diagnosed annually with colorectal cancer are likely candidates for Avastin. Therefore, within about three years, Avastin sales could reach $1.4 billion, he said.

Meanwhile, Jason Kantor, managing director with W.R. Hambrecht & Co in San Francisco, told BioWorld Today his rough sales estimates for Avastin in 2004 (if approved in March) total $250 million, rising to about $500 million in 2005. He also believes Avastin potentially could be a blockbuster, particularly when other indications, like renal cell carcinoma, are added to the label.

King's $1.4 billion estimate includes off-label use in breast, lung and kidney cancer.

Genentech is expected to launch Avastin soon after FDA clearance. "We plan to get it out the door as soon as possible," Sweeney said. "After we saw the data back in May, we realized this is something we need to get to patients just as quickly as we can, so we have plans in place to do that."

Avastin served as a springboard for Genentech in May, pushing the company's stock up 44.7 percent to close at $54.85 on the day the company released positive data from a 900-patient Phase III trial. The company reported that the Phase III "far exceeded" what it was designed to demonstrate. (See BioWorld Today, May 20, 2003.)

Genentech's stock (NYSE:DNA) on Monday dropped 39 cents to close at $80.

Results from the Phase III trial were significant to others working in the anti-angiogenesis arena because it was the first time positive data had come from such a product in cancer. Genaera Corp., EntreMed Inc., Regeneron Pharmaceuticals Inc. and Protein Design Labs Inc. also work in the area and their share prices benefited from Genentech's news.

The Genentech Phase III study randomized 800 patients to receive Avastin plus chemotherapy (5-FU/leuocovorin/CPT-11, also called the Saltz regimen) or the Saltz regimen plus placebo. A third arm treated 100 patients with Avastin plus chemotherapy, although that arm was dropped when safety was established with the Saltz regimen.

Genentech said analysis on a second study of Avastin in metastatic colorectal cancer is expected to be completed in the fourth quarter. That trial includes 200 patients with first-line metastatic colorectal cancer who were randomized to receive either 5-FU/leucovorin chemotherapy alone or in combination with Avastin.

Beyond metastatic colorectal cancer, Genentech has enrolled about half the 700 to 800 targeted patients scheduled for a Phase III trial in lung cancer. Another Phase III is being enrolled in breast cancer, and the company expects to begin enrollment of a Phase III kidney cancer study later this year. A previous Phase III in breast cancer missed its primary endpoint of progression-free survival in relapsed metastatic breast cancer, but hit a secondary endpoint in overall response rate. (See BioWorld Today, Sept. 11, 2002.)

Also, Sweeney said smaller studies in pancreatic, ovarian and prostate are under way.

F. Hoffmann-La Roche Ltd., of Basel, Switzerland, which owns an interest in Genentech, picked up its option to non-U.S. rights to Avastin. Sweeney said Roche would owe Genentech royalties on sales outside the U.S. (See BioWorld Today, July 9, 2003.)