Editor

Among the headliners at the upcoming meeting of the American Society of Clinical Oncology are details on the eye-opening success of Genentech Inc.'s vascular endothelial growth factor drug Avastin (bevacizumab) in Phase III trials for metastatic colorectal cancer and long-awaited word regarding scandal-plagued ImClone System Inc.'s cancer drug Erbitux.

But that's hardly all.

Investors who have had enough of that are likely to hear plenty of other news to pique their interest. Those in the cancer drug arena have cause to anticipate a more upbeat ASCO meeting than last year's, which contained little enough to cheer about. Erbitux, for example, proved disappointing in a Phase II trial in combination with cisplatin in treating refractory squamous-cell head and neck cancer. A host of other companies failed to shine, too. (See BioWorld Financial Watch, May 27, 2002.)

This year, however, at least a few firms among the army of those presenting could come up winners - even if many are cast into the shadow by the still-resounding Avastin results.

"Avastin's got center stage all to itself," said Michael King, analyst with Banc of America Securities. "Everything else is secondary to that."

The ASCO event, which takes place May 31 through June 3 in Chicago, will feature more about Avastin, an anti-angiogenesis treatment for which hopes had been low. King, in fact, issued a research report predicting failure, just ahead of the news about the Phase III data.

"My timing was unique," King said. Genentech's stock soared 44.7 percent on news that the trial with Avastin had "far exceeded" expectations based on the design of the study. Other companies with anti-angiogenesis treatments in the works saw their shares rise, too.

King quickly reversed his Genentech "sell" advice to "buy," and in the days following was met with understanding among investors and his peers in an unpredictable industry.

"I actually got some reasonably positive feedback," he told BioWorld Financial Watch. "People respected the fact that I could admit I was wrong.

"Luckily, no one got hurt," he added.

As for ImClone and Erbitux, ASCO will highlight long-awaited data from overseas partner Merck KGaA's trial with the drug - which are slated for disclosure days before former ImClone CEO Samuel Waksal is sentenced for bank fraud and securities fraud.

His brother, Harlan Waksal, had taken over as president and CEO, but switched jobs to chief scientific officer at the end of April when an internal review began probing ImClone's failure to withhold $60 million in taxes on executive stock options.

Things went bad for ImClone about a year ago when Samuel Waksal and home-decorating maven Martha Stewart were accused of selling stock ahead of notification from the FDA that it would not accept the rolling biologics application for Erbitux.

The dismal beat goes on for ImClone (which has partnered Erbitux in the U.S. with Bristol-Myers Squibb Co.), but those with hope remaining are looking with optimism to the Merck data. If the results are positive, ImClone could file for approval again and possibly have Erbitux on the market by 2004.

Another possibility is that the data will be good but not good enough for Erbitux as a combination therapy, which means ImClone would have to go the single-agent route in its bid for approval. Merck is evaluating the combination of Erbitux and irinotecan vs. Erbitux alone.

But, whatever the controversy surrounding ImClone's leadership, the FDA has not looked with universal disfavor upon Erbitux as a drug, and observers note the compound could have a clear shot at approval as a single agent. (See BioWorld Financial Watch, Jan. 28, 2002.)

One of the products deemed likely to have a good showing, ABX-EGF, is closing in on Erbitux, a monoclonal antibody designed to target and block the epidermal growth factor receptor. Abgenix Inc. and partner Amgen Inc. are expected to report preliminary data from the first 40 patients enrolled in a 100-patient Phase II trial of ABX-EGF, also a monoclonal antibody inhibitor of the EGF receptor being tested in refractory colorectal cancer. If the results are worthy, showing a 15 percent to 20 percent response rate (which would beat Erbitux's numbers as a monotherapy), the companies could move into Phase III next year.

EGFR work gained a big credibility boost earlier this month when the FDA approved Iressa (gefitinib), AstraZeneca plc's EGFR tyrosine kinase inhibitor pill for advanced non-small-cell lung cancer.

Another EGFR inhibitor, Tarceva (erlotinib HCl) from OSI Pharmaceuticals Inc., is expected to be the subject of a report on the Phase II trial in colorectal cancer. How those numbers might fall is uncertain; in April, Genentech said a data safety monitoring board said the drug should be stopped for patients after the disease progresses in a Phase III trial with Tarceva as a front-line therapy.

But observers are holding out for a favorable showing by Tarceva as a third-line approach and against glioblastoma. For the latter, Phase I data are expected at ASCO.

Already in Phase III trials (and out of them) is MGI Pharma Inc.'s palonosetron, an agent designed to prevent chemotherapy-induced nausea and vomiting. The company has reported the drug met its primary and secondary endpoints in a Phase III program of 1,800 patients that included three pivotal trials. At ASCO, more Phase III data will compare the drug to GlaxoSmithKline plc's Zofran (ondansetron) or Aventis Pharmaceuticals Inc.'s Anzemet (dolasetron mesylate).

A gloomy note may sound with the complete analysis of data from Isis Pharmaceuticals Inc.'s Phase III trial of Affinitak, which failed in March. Results of the non-small-cell lung cancer trial showed the antisense drug did not meet its primary endpoint of a difference in primary log-rank analysis of survival vs. control. Isis' partner, Eli Lilly and Co., has stopped enrollment of a similar Phase III study. In April, Isis said it was reducing staff and cutting programs to save money.

Although one of the casualties of that move was a delay in development of ISIS-2503 for pancreatic cancer - which recently met its endpoint in preliminary analysis of Phase II data - Isis will offer Phase II numbers for the antisense inhibitor of h-ras in pancreatic and metastatic breast cancer at ASCO.

"Velcade will get a fair bit of attention," King predicted, referring to Millennium Pharmaceuticals Inc.'s bortezomib, a proteasome inhibitor for multiple myeloma approved earlier this month. So will Revimid, he said, which is the analogue of Celgene Inc.'s approved Thalomid (thalidomide), which also is used against multiple myeloma. (See BioWorld Financial Watch, May 19, 2003.)

The avalanche of news due at the ASCO meeting - much of it potentially good, at late stages and early stages, with incremental data and pivotal data - will keep investors more than a little interested.

"This is going to be fun," King said.