Washington Editor

Abgenix Inc. and partner Amgen Inc. are starting a pivotal trial for use of ABX-EGF as a third-line monotherapy in colorectal cancer patients.

The companies believe the pivotal trial could be the basis of their biologics license application expected to be filed under the FDA's accelerated approval guidelines. Enrollment should begin shortly.

Ami Knoefler, director of corporate communications and investor relations for Fremont, Calif.-based Abgenix, told BioWorld Today the companies would not release specific details about the design of the pivotal trial, including its endpoints or the number of people it would enroll, for competitive reasons. However, she mentioned that accelerated approval guidelines would allow the partners to win FDA clearance based on a surrogate endpoint.

"This [trial] is part of a broad oncology development program for the drug that includes multiple tumor types, as well as monotherapy and combination therapy for colorectal cancer," Knoefler said.

A second pivotal trial is being initiated in Europe as part of a global development program for the candidate.

Trish Hawkins, spokeswoman for Thousand Oaks, Calif.-based Amgen, would not discuss the ABX-EGF program either, saying the partners would release additional information at a later date.

Meanwhile, Alex Hittle, a biotechnology analyst with AG Edwards in St. Louis, characterized the third-line study as a trial meant to get the candidate to market. "Sometimes you start in late-stage indications and work your way back," Hittle said. "If this is a place where they can get the drug approved, then they can start looking for possible off-label expansion."

ABX-EGF, developed with Abgenix's XenoMouse technology, is directed against the epidermal growth factor receptor (EGFR), a receptor that lies on the outer surface of many cells. The receptor is a prime target for cancer agents because it is overexpressed in a number of the most common human tumor types.

As per a revised co-development agreement between the companies, Amgen has the primary responsibility for running the trials, while Abgenix will handle manufacturing. Amgen inherited the relationship via its purchase of Seattle-based Immunex Corp., but recently updated it, clarifying responsibilities and providing Abgenix with access to $60 million to fund its share of development costs. (See BioWorld Today, July 28, 2000.)

Beyond colorectal cancer, ABX-EGF is in Phase II trials for non-small-cell lung cancer, renal-cell cancer and prostate cancer.

Other EGFR inhibitors are Erbitux, made by ImClone Systems Inc., of New York, and Iressa, made by London-based AstraZeneca plc. Last year Iressa (gefitinib) won FDA approval under accelerated approval guidelines as a treatment for advanced NSCLC. AstraZeneca is studying the product in other indications. (See BioWorld Today, May 6, 2003.)

Meanwhile, ImClone waits for an FDA decision on Erbitux (cetuximab).

Hittle said Abgenix makes the claim that ABX-EGF is at an advantage because it is less immunogenic, so the body is not as likely to fight it off.

"There may be some advantages compared to an Iressa, which is on a different point on the EGF receptor pathway," he said. "Iressa acts inside the cell, whereas the Abgenix and ImClone products are hitting the receptors on the surface. But it is too early to tell which approach is better. It is going to depend a little on mutations that characterize different patient's cancers."

Nevertheless, Hittle said it does seem that ABX-EGF and Erbitux have more benign profiles, which could permit higher dosing than Iressa.

Abgenix's stock (NASDAQ:ABGX), stock closed Monday at $14.99, down 36 cents, while Amgen's (NASDAQ:AMGN) closed at $62.95, down 55 cents.