Editor

Although the American Society of Clinical Oncology meeting in Orlando, Fla., which wrapped up last week, spewed much data and generated plenty of talk, the news wasn't all good for biotechnology firms, nor was it all bad. In a down market, however, the word "mixed" doesn't carry quite the cautious optimism it once did at least not for those with cash on the line.

"This year's meeting was certainly a disappointment, in their view," said Jason Zhang, analyst with Stephens Inc., although cancer specialists tend to go into the meeting each year with an altogether different perspective.

"From an oncologist's point of view, these are not huge setbacks," he noted. "They see [the whole picture] in increments."

Such might be a hard sell to Protein Design Labs Inc., which said it is dropping development of Zamyl, a humanized antibody that binds to the CD33 antigen on myeloid leukemia cells, after it failed to show statistical significance in an acute leukemia Phase III trial, data from which was detailed at the ASCO meeting. The missed endpoint had been disclosed in December.

Even more dispiriting to many were the mixed results from ImClone Systems Inc. on trials with its FDA-stalled Erbitux (cetuximab), which Zhang called "the biggest disappointment."

ImClone and its partner, Bristol-Myers Squibb Co., offered data from an Erbitux Phase II trial in combination with cisplatin in treating refractory squamous-cell head and neck cancer. Nine of the 78 evaluable patients in the trial (11.5 percent) achieved a partial response and 13 patients (16.7 percent) achieved stable disease, for an overall rate of disease control of 28.2 percent.

The companies also presented results from a study of Erbitux with docetaxel in patients with advanced non-small-cell lung cancer. The study enrolled 75 patients with advanced forms of the cancer who had progressive disease during, or disease recurrence within, three months of chemotherapy. Of the 30 evaluable patients, eight (26.7 percent) achieved a partial response and eight achieved a stable response. The overall rate of disease control was 53.4 percent.

Data from studies suggest Erbitux has antitumor activity as a single agent in chemotherapy-resistant colorectal cancer, the companies said, and shows potential in combination with irinotecan, fluorouracil and leucovorin.

A Phase II trial of 57 patients testing Erbitux as a single agent for refractory colorectal cancer found six patients (10.5 percent) achieved a partial response and 21 (36.8 percent) achieved stabilization of disease. The overall rate of disease control was 47 percent in the trial.

"We thought the head and neck trial should give them good activity, but it wasn't that significant," Zhang said.

Later in the week, amid news reports of ImClone starting necessary new trials of Erbitux in the U.S., CEO Samuel Waksal resigned.

"I think they've come back to ground zero now," Zhang said. "They were very aggressive with their clinical program, and those plans actually ended up hurting them. If they had planned better trials, they could have been on their way to getting indisputable data."

There were bright spots. Amgen Inc. offered encouraging data regarding its anemia product Aranesp (darbepoetin alfa), already approved in September for dialysis and nondialysis patients with chronic renal failure, and being used off-label for cancer patients. The company said it has begun to enroll a large Phase III "loading" study, wherein patients are given larger amounts of the drug at first and then kept on a maintenance dose.

Extended-release Aranesp allows for fewer injections than epoetin alfa, which is marketed as Epogen by Amgen and as Procrit by licensee and competitor Johnson & Johnson.

Genentech Inc. shared positive results from a Phase II trial in kidney cancer with its anti-angiogenesis monoclonal antibody Avastin (bevacizumab), and the company said it plans to begin Phase III after talks with the FDA. Phase III studies already are under way in colorectal and breast cancers.

"There was a lot of talk about toxicity, prior to the meeting," Zhang said. "Yes, it has toxicity, but I think that was overblown."

The Phase II study of 116 patients showed that patients with metastatic kidney cancer treated with 10mg/kg of Avastin every two weeks had a statistically significant increase in the primary endpoint compared to placebo patients.

That endpoint time to disease progression is the same in the breast cancer trial, and could be a sticking point, although the FDA hasn't made the case clear yet.

In any case, data from that Phase III colorectal cancer study, with 900 patients and survival as an endpoint, are due next year, and that trial has survival as its endpoint. The study is comparing Avastin plus CPT-11/5-FU/leucovorin the Saltz regimen to the Saltz regimen alone.

Other happy notes included Inex Pharmaceuticals Corp., which disclosed interim results from an ongoing trial of its lead product, the targeted chemotherapeutic Onco TCS, in non-Hodgkin's lymphoma. All 26 patients responded to treatment with the drug, and all but one had their tumors eliminated. The other patient's tumor volume decreased by more than 50 percent.

ILEX Oncology Inc. has a different drug, Clofarex (clofarabine), a nucleoside analogue for leukemia. Clofarex "demonstrated better results than the original abstract disclosed," Zhang wrote in a research note. Tested for acute leukemia in patients who failed chemotherapy, it achieved impressive complete remission rate of five out of 20, or 25 percent. The abstract had reported only three complete remissions.

"We also learned from our conversations with several physicians at the meeting that the Phase II trial [which could become a pivotal Phase II trial] should start to enroll patients imminently, which, in our opinion, will be a positive catalyst for Ilex's stock," Zhang wrote.

Inex is "probably overlooked by a lot of people," he told BioWorld Financial Watch. "People who have failed all types of chemotherapy have shown a good response rate. The stock hasn't been picked up by a lot of analysts."

A company "in the same ballpark," he said, is Telik Inc., which offered preliminary results of a Phase II trial of TLK286, a small molecule activated by glutathione S-transferase (an enzyme that is overexpressed in many human cancers), in patients with advanced, platinum-resistant, non-small-cell lung cancer. The drug showed single-agent antitumor effects in patients with highly resistant disease. In another trial, it showed good results against advanced ovarian cancer.

In a Phase I dose-escalation trial, TLK286 was given weekly and was well tolerated, showing still more evidence of clinical benefit which is important but, as apparently proven by ImClone, it's not the only thing, Zhang said.

"We have a clear picture of what [Telik] is going to do with the drug, and that's what we look for," he said. "We learned from them they're going to do everything to conduct [their trials] right."

Investors were left wary after the ASCO meeting, Zhang said.

"It's not fair to expect a major breakthrough every year," he said. "There are people who know this field really well, and they will go to [ASCO and] talk to doctors about clinical parameters," and other such technical matters.

Outside the scientific arena, though, the situation given the bleak market is different. "Particularly right now, people have a short attention span," Zhang said. "They're not going to focus too much, and I don't blame them. They haven't been burned like this for a couple of years."