Staff Writer

Abgenix Inc.'s stock surged 37.7 percent Thursday following news that its EGFr inhibitor, panitumumab, significantly improved progression-free survival in a pivotal metastatic colorectal cancer study.

The top-line data shook up investors of ImClone Systems Inc., the New York-based company that markets Erbitux for the same indication. ImClone's shares (NASDAQ:IMCL) fell 20.6 percent, or $7.46, to close at $28.65.

Fremont, Calif.-based Abgenix and partner Amgen Inc., of Thousand Oaks, Calif., now are poised to complete a rolling biologics license application submission in the first quarter of 2006 - and investors are wondering if panitumumab can capture some of the colorectal cancer market that Erbitux addresses. That product, an IgG1 monoclonal antibody that binds specifically to epidermal growth factor receptors (EGFr), had $107 million in net sales for the quarter ended Sept. 30.

"The data for panitumumab are in third-line colorectal cancer, and we now estimate Erbitux has about a third of that market," said Joel Sendek, an analyst with New York-based Lazard Freres & Co. LLC. "So it will definitely compete with Erbitux."

Erbitux is a genetically engineered version of a mouse antibody that contains both human and mouse components. Panitumumab, an IgG2 monoclonal antibody, is the first fully human monoclonal antibody that targets EGFr. Co-developed with Amgen, it was generated with Abgenix's XenoMouse technology to create an antibody that contains no murine protein, minimizing immune system infusion reactions and allergies.

Sendek projects that a launch for colorectal cancer could occur in 2007 or earlier, depending on how quickly the FDA reviews the BLA. He estimates $100 million in sales for 2007, and "we think that number could double or triple a couple of years after that."

While ImClone's stock took a hit on the panitumumab data, no head-to-head study with Erbitux has ever been conducted that shows one is better in terms of efficacy.

"We can't really discern any differences in the data. We haven't seen it all yet," Sendek told BioWorld Today. "But there are elements of panitumumab that theoretically make it a more attractive alternative, including potential for less frequent dosing, the lack of a need to pretreat when you dose it and a theoretical safety advantage because it's a fully human antibody."

Erbitux also is being developed for lung, pancreatic and ovarian cancers, and ImClone recently filed an sBLA for Erbitux to treat head and neck cancer. (See BioWorld Today, Aug. 31, 2005.)

Like Erbitux, panitumumab is being developed for expanded indications as a monotherapy and in combination with other agents to treat colorectal, lung and kidney cancers.

The data released Thursday came from a randomized Phase III trial involving 463 metastatic colorectal cancer patients who had failed standard chemotherapy, including oxaliplatin and irinotecan. Those who receive panitumumab every two weeks showed a 46 percent decrease in tumor progression rate compared with those who received best supportive care alone (p<0.000000001).

The results far surpassed the expectations of anyone at Abgenix or Amgen, as the trial was designed to demonstrate a decrease of 33 percent, as assessed by central radiology review.

"I think it is, in my mind as an oncologist, very significant news," said Gisela Schwab, Abgenix's chief medical officer. "The study was conducted in patients who have failed all available chemotherapy, so for this patient population, there is a clear unmet medical need."

Abgenix's stock (NASDAQ:ABGX) climbed $3.53 to close at $12.90, while Amgen's stock (NASDAQ:AMGN) rose $3.61, to close at $77.51.

Panitumumab also met its secondary endpoint of objective response rate, and adverse events were consistent with previous clinical studies. Side effects included acneiform rash, the most common one experienced, as well as fatigue, nausea and mild diarrhea. No anti-human antibody or anti-panitumumab antibody formation was observed.

Conducted in Europe, Australia and Canada, the Phase III trial randomized patients to receive panitumumab plus best supportive care or best supportive care alone. Panitumumab was delivered by an intravenous infusion of 6 mg/kg once every two weeks, and patients did not need any premedication before the administration.

Best supportive care included antibiotics, analgesics and radiation therapy for pain control, as well as corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery and any other symptomatic therapy. It did not include anticancer chemotherapy.

Abgenix introduced panitumumab to the clinic in late 1999, and partnered it with Immunex Corp. in 2000 in a 50/50 cost and profit-sharing arrangement. Amgen later acquired Immunex in a deal initially valued at $16 billion and completed in July 2002.

"Amgen has conducted the late-stage clinical development," Schwab said. "Abgenix is in charge of manufacturing panitumumab."

The companies expect to present complete analyses of the data at a medical meeting in 2006. An analysis of overall patient survival will occur about 12 months after the last patient was randomized, sometime in the second quarter of 2006.