National Editor

Colorectal cancer - the devilish killer that can show up in the hidden places implied by its name, as well as the appendix and anus - remains the second leading cause of cancer deaths among men and women combined, behind only lung cancer in the U.S.

About 147,000 new cases are expected to be diagnosed this year, and more than 56,000 patients will die from colorectal cancer (CRCA), a sad state of affairs that opens the door wide for Avastin (bevacizumab) and Erbitux (cetuximab). Uptake of both on the market are "tracking ahead of our and [Wall Street's] expectations," according to research by SG Cowen & Co. in New York.

"It's clear already there are multiple lines of therapy as opportunities," said Joshua Schimmer, an associate with Cowen. "It would seem that [physicians] have adopted Avastin front line and Erbitux second line."

South San Francisco-based Genentech Inc.'s Avastin, the vascular endothelial growth factor inhibitor that has rocked the cancer world, is getting more popular in metastatic CRCA, Cowen found. A pair of expert consultants told Cowen analysts in a conference call last week that they are using Avastin as front-line therapy in 90 percent and 100 percent of patients, respectively - topping by far the averages from a Cowen survey, in which physicians said they treated 23 percent of first-line patients with Avastin during April. Those polled estimated they would be using Avastin for 58 percent of patients as first-line therapy in six months.

"As thought leaders at academic centers, these [two] clinicians are going to be early adapters," Schimmer told BioWorld Today, calling them trailblazers in the field. "We can expect the rest of the oncology community to follow along on a more delayed schedule," he added. The experts typically prefer not to be identified or quoted directly, Cowen analyst Eric Schmidt told BioWorld Today.

The question, of course, is how fast they follow along.

"We tried to get a sense of that in our survey, and we put those numbers into our estimates," Schimmer said. Cowen expects Avastin for CRCA to sell $378 million this year and Erbitux $175 million.

Erbitux, from ImClone Systems Inc., of New York (which is developing Erbitux with Bristol-Myers Squibb Co., also of New York, and Darmstadt, Germany-based Merck KGaA), was said by the experts to be moving from refractory third-line CRCA patients to second-line therapy.

Common for use in patients who have failed with Avastin therapy, Erbitux is being used mostly as a second-line agent with irinotecan-based chemotherapy by Cowen's consultants, who said they were administering the drug in more than 75 percent of patients at that stage. Again, the number is well ahead of Cowen's tracking survey, which showed doctors treating 1 percent, 12 percent and 23 percent of their first-, second- and third-line patients, respectively, with Erbitux.

At the American Society of Clinical Oncology (ASCO) meeting coming in June, ImClone is due to present data from a single-agent trial testing Erbitux in refractory patients, and Cowen's experts said they expect the data to be similar if not better than the data from Merck's eye-opening BOND trial, offered at the 2003 ASCO meeting. (See BioWorld Today, June 3, 2003.)

Seen as promising by the experts is SU-011248, the oral tyrosine kinase inhibitor from Sugen Inc., a unit of Pharmacia Corp. (now part of New York-based Pfizer Inc.), which also is being investigated for renal cancer. (See BioWorld Today, May 24, 2004.)

A Phase II study with the Sugen drug is enrolling CRCA patients who have failed both oxaliplatin and irinotecan, who will be given SU-011248 plus or minus Avastin. Another is enrolling to investigate the drug in patients who have failed the standard of care including Avastin. Pointing to activity in neuro-endocrine cancers, Cowen's physicians held out hope the drug could show single-agent activity - as Avastin did not.

"It's probably still a little bit early to get a good read as to how it's going to work," Schimmer said, noting the Sugen drug's different mechanism of action. "It hits multiple targets, and because of that it may have some kind of incremental benefit for the refractory population."

The experts were not as enthusiastic about ABX-EGF, the Phase III fully human monoclonal antibody for refractory CRCA from Thousand Oaks, Calif.-based Amgen Inc. and Abgenix Inc., of Fremont, Calif. Data are not significantly different from Erbitux, the experts said.

"The dose administration, we're hearing, could be a little less frequent, and you could potentially reduce the infusion reactions," Schimmer said, but the experts believe that ABX-EGF, by the time it's cleared by the FDA, "could be facing a crowded market."

Another drug, EMD-72000 from Merck, has shown some encouraging efficacy in gastric cancer, the experts noted, and could separate itself from Erbitux and ABX-EGF, but might be hard pressed to do so.

A therapy that could stand out, however, is PTK787, from Novartis AG, of Basel, Switzerland, and Schering AG, of Berlin, being tested in Phase III trials in combination with first- and second-line chemotherapy for patients with metastatic CRCA.

PTKT787 is "somewhat similar to the Sugen drug, in that it's another oral VEGF inhibitor that hits more than one target." Data are expected in 2005, and Cowen's experts view the drug as "an important challenger" in the CRCA market.

Meanwhile, "we believe there's upside for both Avastin and Erbitux," Schimmer said, and the upcoming ASCO meeting in New Orleans is likely to show that.

"We're not going to get everyone saying 100 percent usage [for Avastin]," Schimmer said, "but we expect the investment community to be very impressed."

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