Larger 1st-stage drug trial defended


EntreMed Inc. said yesterday that it would expand early-stage testing of its highly publicized anti-tumor drug Endostatin by adding 12 patients to a clinical trial in Boston, a move the company said was an option under its original plan but that one analyst called "a little odd."

"To a skeptic, they would say adding more patients means you are not happy with what you've seen so far," said Alan Auerbach of First Security Van Kasper in Los Angeles. "It's a little odd to see this occur."

EntreMed executives disputed that, however, saying plans for such clinical trials almost invariably include the option of adding more patients. And Auerbach hastened to add that he hasn't reached a conclusion about what the trials portend for Endostatin. He urged investors to treat the expansion as a "nonevent and wait for the data."

Most investors appeared to heed that advice yesterday: Shares of EntreMed closed regular Nasdaq trading at $33.50, down 50 cents, or .47 percent. The Rockville company plans to release results of the trials at a November scientific gathering.

Endostatin, a protein which has been shown to shrink tumors in mice by attacking tumor-feeding blood vessels, is in Phase I trials - tests on humans designed to show whether a drug is safe and to help determine proper dosage.

Though such early trials aren't designed to show how well a drug works, speculation on the effectiveness of Endostatin has abounded.

James D. Watson, one of the discoverers of DNA's structure, raised hopes early when he was quoted in a 1998 New York Times article as saying Endostatin and another anti-tumor protein developed by Dr. Judah Folkman of Children's Hospital in Boston were possible cures for cancer. The comments sent EntreMed's shares soaring 330 percent - before testing of Endostatin on humans had even begun.

In May, the stock dove more than 30 percent in one day after Dr. James Pluda, a lead investigator at the National Cancer Institute, said he had seen "no major clinical response in patients" who had taken it. Pluda clarified his remarks the next day, noting that Phase I trials aren't designed to prove a drug's effectiveness.

Yesterday, EntreMed executives declined to comment on whether Endostatin has shrunk or halted tumor growth in patients, saying any such comments would be premature.

Edward R. Gubish, EntreMed's executive vice president, said the trials were expanded to better understand how the protein reacts in humans at various doses.

While trials usually are expanded because of unwanted side effects, that isn't the case with Endostatin, which has been well-tolerated by patients, executives said.

The Boston trials begun in late March enrolled patients in five groups of three patients each. They began at various Endostatin doses, which were then raised. "Three patients is not enough for us to draw significant conclusions," said Gubish, who heads EntreMed's research and development efforts.

The trials are taking place at Dana-Farber/Partners CancerCare - a consortium of hospitals in Boston - as well as at the M. D. Anderson Cancer Center in Houston and at the University of Wisconsin Comprehensive Cancer Center in Madison.

EntreMed is sponsoring the trials in Boston; the National Cancer Institute is overseeing the trials in Houston and Madison. At least 49 patients have received Endostatin - which is administered intravenously - at the three sites.

Endostatin is one of at least 18 drugs known as "angiogenesis inhibitors" being studied. The drugs - including EntreMed's Angiostatin and 2-Methoxyestradiol - aim to block blood vessel growth.

Some analysts and scientists believe that the drugs hold the most promise to fight cancer if used in conjunction with other, traditional therapies. Accordingly, EntreMed last week began a Phase I trial of Angiostatin in conjunction with radiation. That trial is taking place at Thomas Jefferson University Hospital in Philadelphia.

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