National Editor

CHICAGO - With drugs already on the market for two side effects of chemotherapy - anemia and infection - Amgen Inc. disclosed data from a pivotal Phase III trial of palifermin for another onerous consequence of chemo: mucositis.

"About 40 percent get a pretty serious case of it," said Michael Beckerich, spokesman for Thousand Oaks, Calif.-based Amgen, adding that he has met a few afflicted patients.

"It's nasty," he said. "Mouth sores, their faces are white, they can't swallow, they can't eat" - and, potentially worse, they may not feel like going on with their chemo.

Data from the Phase III trial with palifermin, a recombinant human keratinocyte growth factor, were disclosed at the American Society of Clinical Oncology meeting here. Keratinocyte growth factor stimulates proliferation of cells in the mouth and gastrointestinal tract.

Palifermin compared to placebo significantly reduced the duration and incidence of severe oral mucositis in patients with hematologic malignancies undergoing high-dose chemotherapy, radiotherapy and total body irradiation followed by hematopoietic stem cell support.

Its effectiveness was "three times that of placebo, which is pretty significant considering there's no medication out there to treat this," Beckerich told BioWorld Today. The ratio was 62 percent vs. 20 percent.

Patients were randomized to get either palifermin (106 patients) at a dose of 60 mcg/kg per day or placebo (also 106 patients) for three days before high-dose chemotherapy and total body irradiation. All patients then received peripheral blood progenitor cell transplants, followed by three more days of either palifermin or placebo.

Not only did the palifermin patients have a lower incidence of severe mucositis, but those who had the condition experienced almost one week less severe mucositis than those given placebo: 10.4 days vs. 3.7 days. Palifermin patients also reported 60 percent less soreness of the mouth and throat, and required lower doses of painkillers, along with less use of parenteral (intravenous) nutrition.

When many patients are diagnosed with cancer, "they're in shock, thinking, Oh my God, I'm going to die,' and they ask for the most aggressive treatment," Beckerich said. "The patients aren't really focused on the side effects."

A pre-biologics license application with the FDA for palifermin is expected in the third quarter of this year. Amgen already has Neulasta (pegfilgrastim), used to decrease infection during chemo, and Neupogen (Neulasta's first and shorter-acting version). For anemia, the company has Aranesp (darbepoetin alpha), which competes against New Brunswick, N.J.-based Johnson & Johnson's version of epoetin alfa, called Procrit.

Aranesp also was the subject of ASCO news over the weekend. Amgen offered data from seven studies, including its massive Successful Outcomes in Anemia Research trial, in support of extended dosing compared to other treatments.

"Procrit, the standard of care in chemotherapy-induced anemia, is dosed once per week at 40,000 units," Beckerich said. "We knew 85 percent of Aranesp use by oncologists has been every other week. Most oncologists were using it in this fashion, but [the Centers for Medicare and Medicaid Services] didn't have the data," since that use is off label, he said.

"Now, we have 1,200 patients in this big SOAR trial, showing that it works every other week just as well as Procrit with half the shots," Beckerich said.

Specifically, 1,173 patients with chemo-induced anemia who got 3.0 mcg/kg (200 mcg for the average patient) showed a clinically significant increase in hemoglobin. Another study yielded clinically significant improvements in patient-reported fatigue and energy scores.

Because they get half as many injections as with Procrit, patients "get reminded half the time they have cancer, and they get half the pain of the injection," Beckerich said. They also spend less time in doctors' offices, reducing administrative expenses.

"If you compare the price of Aranesp every other week to Procrit once per week, on a monthly basis it's about 9 percent, 10 percent less, and that's just the cost of the drug," he said.

Another ASCO presentation dealt with a comparison of SOAR data with data from patients treated with epoetin alfa in other clinical trials. Analysis suggests the clinical outcomes in treating chemo-related anemia - that is, hematopoietic response, mean hemoglobin change after four weeks and 12 weeks, and the proportion of patients who need red blood cell transfusions - were similar between Aranesp every two weeks and epoetin alfa once a week or three times per week.

Amgen also is experimenting with "front-loading" Aranesp, Beckerich said, which means giving "a lot of drug up front, getting [patients] corrected quickly, and then maintaining them on an every three-week or every four-week basis." That was the subject of four posters at ASCO.

"We're finding the responses are much faster and it lasts," he said. "What we're trying to figure out is, what's the proper dose? We've done a variety of big Phase II studies and we need to do a big Phase III."

Beckerich said the company is "trying to find better ways. We don't really look at it as a battle between two drugs. It's what's working better."

Amid all the colorectal cancer data flying around at ASCO, Amgen checked in with some of its own. Interim Phase II data from a study of ABX-EGF showed the EGFR drug partnered with Abgenix Inc., of Fremont, Calif., yielded either partial tumor responses or stabilized disease.

In the planned analysis of the ongoing trial, 44 patients were evaluated on an intent-to-treat basis and 40 were efficacy-evaluable after eight weeks of treatment. Patients had measurable disease and had been treated previously with 5FU (with or without leuvocorin) and with irinotecan or oxaliplatin or both.

The subjects were given 2.5 mg/kg of ABX-EGF by intravenous infusion weekly for an eight-week treatment cycle - up to six cycles. At the end of the first cycle, four of the 40 patients had partial responses and 22 had stable disease. All others had progressive disease.

Enrollment of the study's 100 patients is under way and a cohort of 50 patients is being added, with all 150 expected to accrue shortly.

"There has been lots of good news in the colorectal area," said Beckerich. "Amgen is certainly in the game on this."

The company's stock (NASDAQ:AMGN) closed Monday at $63.55, down $1.19. Abgenix's shares (NASDAQ:ABGX) ended the day at $9.71, down 93 cents.