Taking a different approach with their metastatic colorectal cancer drug panitumumab, Amgen Inc. and Abgenix Inc. started another Phase III trial of the therapy, this time as a first-line treatment administered with bevacizumab and chemotherapy.
The companies initiated two pivotal trials, one in the U.S. and one in Europe, in January 2004, testing panitumumab (formerly ABX-EGF) as a third-line monotherapy. (See BioWorld Today, Jan. 21, 2004.)
The strategy initially is to file a biologics license application for panitumumab as a third-line monotherapy later this year, then expand the label to a first-line combination treatment down the road, said Trish Hawkins, Amgen's spokeswoman.
Both Amgen and Abgenix have kept relatively mum about the design of those first two trials for competitive reasons. The ex-U.S. trial, being conducted in Europe, Australia and Canada, completed enrollment last month with more than 460 patients. While enrollment of the U.S. trial is continuing, the endpoints of the trials have not been disclosed.
The new trial will enroll about 1,000 patients and evaluate endpoints such as progression-free survival, overall survival and response rate.
"The study's duration will depend on how long it takes to fully enroll and how long patients experience potential benefits of the treatment regimen," Hawkins told BioWorld Today.
Panitumumab will be administered every other week with bevacizumab and an oxaliplatin-based or irinotecan-based chemotherapy. Bevacizumab is better known as Avastin, South San Francisco-based Genentech Inc.'s colorectal cancer drug, which had sales of $555 million in 2004. The oxaliplatin- and irinotecan-based chemotherapies that will be used in the trial are Paris-based Sanofi-Aventis Group's Eloxatin and New York-based Pfizer Inc.'s Camptosar, respectively.
The randomized, open-label trial has been named PACCE (Panitumumab Advanced Colorectal Cancer Evaluation).
Thousand Oaks, Calif.-based Amgen and Fremont, Calif.-based Abgenix started the PACCE study on the belief that therapies might have a higher success rate in treating patients when used in conjunction with each other. There might be advantages to targeting multiple pathways that aid in tumor survival and growth at the same time rather than targeting only one pathway.
Panitumumab works by inhibiting the epidermal growth factor receptor (EGFr).
Bevacizumab, on the other hand, targets the vascular endothelial growth factor involved in angiogenesis.
While EGFr helps regulate the growth of different healthy cells, it also stimulates the growth of cancer cells. Panitumumab binds to EGFr.
Previous clinical studies have shown that panitumumab is well tolerated. Interim Phase II data demonstrated that objective tumor responses followed treatment with the drug. The companies are evaluating the product as both a monotherapy and in combination with other agents to treat not only colorectal cancer, but also lung and kidney cancers.
"We have a couple of studies going on in lung cancer," Hawkins said. "The most advanced is a Phase II evaluating panitumumab plus carboplatin and paclitaxel."
Panitumumab is generated with Abgenix's XenoMouse technology, which creates a fully human monoclonal antibody that contains no murine protein. Because it is fully human, clinical trials might demonstrate a favorable safety profile with a low incidence of infusion reactions, antigenicity and allergic response.
"What we believe will be the advantage," Hawkins said, "is that the fully human nature of panitumumab minimizes the potential for it to be recognized as foreign by the body's immune system, compared to other monoclonal antibodies that retain some murine protein."
One such product, which would be panitumumab's main competitor, is Erbitux, developed by New York-based companies ImClone Systems Inc. and Bristol-Myers Squibb Co. The product received approval in February 2004 to be used in combination with irinotecan to treat metastatic colorectal cancer patients. Analysts have said the product could reach more than $1 billion in sales. BMS reported $88 million in sales in the fourth quarter.
Amgen and Abgenix first collaborated six years ago when Abgenix agreed to use its XenoMouse technology to produce fully human monoclonal antibodies to an undisclosed Amgen target antigen, in return for up-front fees, milestone and potential royalties. At that time, ABX-EGF was part of an internal Abgenix program in preclinical studies. (See BioWorld Today, April 27, 1999.)
In July 2000, Abgenix partnered the product with Seattle-based Immunex Corp., which was bought by Amgen for $10.3 billion two years later. (See BioWorld Today, July 28, 2000, and July 17, 2002.)
Abgenix and Amgen signed a revised agreement in October 2003 that gave Amgen authority over development and marketing and Abgenix the manufacturing responsibilities for the product. They will share costs and potential worldwide revenues equally. (See BioWorld Today, Oct. 16, 2003.)
According to data from the American Cancer Society, there were more than 140,000 new cases of colorectal cancer in North America last year.
"Colorectal cancer is the third most diagnosed cancer in the U.S. and Canada," Hawkins said.
Abgenix's stock (NASDAQ:ABGX) dropped 8 cents Wednesday to close at $6.87, while Amgen's stock (NASDAQ:AMGN) rose 71 cents to close at $57.91.