Genentech Inc.'s Avastin received FDA approval as a first-line treatment in metastatic colorectal cancer. With the company saying it will launch the product into the eager arms of patients and doctors within three days and sales expectations high, the drug seems bound for biotechnology folklore.
"I think the anticipation was pretty enormous, reflecting from the fact that when we attended ASCO last year, both physicians and patients were anxiously waiting for it," said Sena Lund, biotech analyst with Cathay Financial LLC in New York. "The potential is huge. For right now, I have almost $2 billion in peak sales, five years from launch."
With Avastin being tested in other cancers, that $2 billion in sales could easily balloon, he told BioWorld Today.
"As [other cancer] data come along, it can be larger than $2 billion, but that also depends on the pricing, which we haven't seen," he said, adding that overall, the drug has a potential to climb to $5 billion, if all things played out perfectly for Genentech.
The company disclosed positive Phase III data at last summer's meeting of the American Society of Clinical Oncology (ASCO). Findings showed that patient survival increased through the use of Avastin with the Saltz regimen - a chemotherapy combination of 5-FU, leucovorin and irinotecan. Median survival increased by 30 percent, from 15.6 months to 20.3 months, and the median time to disease progression was 71 percent. (See BioWorld Today, June 3, 2003.)
Avastin (bevacizumab), a monoclonal antibody, is the first anti-angiogenesis product to be approved. It is designed to work by inhibiting vascular endothelial growth factor (VEGF), which stimulates new blood vessel formation, the process of angiogenesis. By inhibiting VEGF, Avastin is thought to interfere with tumor blood supply and thereby affect tumor growth and metastasis.
"This is a whole new way of treating cancer," Genentech spokeswoman Colleen Sweeney told BioWorld Today. "Here's the first approved therapy that uses this approach, so we're very excited."
As were investors. South San Francisco-based Genentech's stock (NASDAQ:DNA) jumped $7.02 Thursday to push its closing price to $103.10.
Genentech now has a chance to make the first splash with an anti-angiogenesis drug. Sweeney said there are 180,000 metastatic colon cancer patients in the U.S. every year, with about 69,000 of those having reached Stage IV, the population studied in the Avastin pivotal trial.
Specifically, the drug was approved to be used in combination with intravenous 5-fluorouracil-based chemotherapy in first-line metastatic cancer of the colon or rectum. Notably, the approval came a month earlier than the scheduled PDUFA date. The company completed its biologics license application at the end of September, soon after which the FDA conferred priority review status on the submission. Sweeney said that Genentech's application, which was filed on a rolling basis, contained safety and efficacy data from clinical trials in other indications to support the product's profile. (See BioWorld Today, Sept. 30, 2003.)
Sapna Srivastava, analyst with ThinkEquity Partners in San Francisco - who also predicts $2 billion in sales based on the colorectal indication and off-label use in kidney cancer - said that when data are as good as what Avastin brought to the approval table, the length of review is more a function of quantity, rather than quality.
"The data were very clear," Srivastava told BioWorld Today. "Any time you show survival, which is the gold standard, [review time] depends on the amount of data. If it took [the FDA] four months to get through all the information, it took them four months."
Anti-Angiogenesis: From Doubt To Market
Not long ago interest in anti-angiogenesis had waned, following clinical failures.
However, when in May Genentech said Avastin had "far exceeded" what it was expected to show in a Phase III trial in metastatic colorectal cancer patients, it not only lifted Genentech's stock by nearly $17 the day the news was made public, it also provided a boost to others working in the field or with Genentech, including Genaera Corp., EntreMed Inc., Regeneron Pharmaceuticals Inc. and Protein Design Labs Inc. Anti-angiogenesis was back on the radar as a platform for fighting cancer. (See BioWorld Today, May 20, 2003.)
The FDA has now had its first look at an anti-angiogenesis product and liked what it saw. Whether that blazes a path for others remains to be seen, but it's hard to believe there could be any negative effect.
"I think it's very positive for other companies," Srivastava said. "We've seen that even with subtle changes, drugs will work in other cancers." She added that Regeneron, which recently signed a potential $485 million deal centered on its VEGF Trap technology with Aventis SA, of Strasbourg, France, has "a lot of lessons to learn from this." (See BioWorld Today, Sept. 9, 2003.)
The VEGF Trap product is a vascular endothelial growth factor antagonist.
Cathay's Lund said the approval should bolster the confidence of others working in the area.
"It definitely confirms the target," he told BioWorld Today, adding that the FDA's nod also should give companies "the courage to keep working."
Genentech Has Hands Full
While the Avastin approval was key for Genentech in 2004, observers also are looking forward to data on Tarceva, an endothelial growth factor receptor inhibitor for non-small-lung cancer patients being developed with Melville, N.Y.-based OSI Pharmaceuticals Inc. and Roche Holdings Inc., of Basel, Switzerland. The first portion of a rolling new drug application was filed in January. Phase III results are expected at the end of the first quarter, Srivastava said. (See BioWorld Today, Jan. 22. 2004.)
Genentech also is developing Lucentis, its anti-vascular endothelial growth factor antibody fragment in Phase III trials for wet age-related macular degeneration.
The company, Lund said, now "has its hands full, from a marketing point of view." Besides Avastin, there is Xolair and Raptiva. Xolair, an asthma drug, was developed with Tanox Inc., of Houston, and Novartis Pharma AG, also of Basel, and received approval in June. Raptiva, a psoriasis drug, received approval in October and is partnered with XOMA Ltd., of Berkeley, Calif. (See BioWorld Today, June 23, 2003, and October 29, 2003.)
For Avastin, Genentech will handle all commercial and marketing duties in the U.S. The product is under review in Europe following a December submission by partner F. Hoffmann-La Roche Ltd., which controls ex-U.S. rights. Roche will pay royalties on sales to Genentech, in which Roche maintains a controlling interest. (See BioWorld Today, July 9, 2003.)
Beyond Thursday's approval, Genentech is looking to push Avastin into further uses. The product is in Phase III trials for lung, breast and kidney cancers, as well as for earlier stages of colon cancer with other chemotherapy combinations. Earlier-stage studies in pancreatic, ovarian, prostate and hematologic cancers are under way as well.
The colorectal cancer approval, though, gives Genentech "a super growth factor for the next couple of years at least," said Lund, whose firm does not have a banking relationship with Genentech, nor does it own shares. "It's good for the patients and good for the biotech industry."