New study confirms controversial ImClone drug effective

CHICAGO --The fortunes of Erbitux, the experimental medicine that brought down the head of ImClone and ensnarled Martha Stewart in a Wall Street scandal, got a boost Sunday from a new study that concluded it helps terminally ill victims of colon cancer.

The new research, conducted in Europe, found that nearly a quarter of patients improved temporarily when they got Erbitux along with standard chemotherapy. The result mirrors the finding of an earlier study sponsored by Imclone Systems.

Because of shortcomings in that earlier study, the Food and Drug Administration refused to accept ImClone's application for approval of the drug. That decision in December 2001 triggered an insider trading scandal.

"For those who were skeptical about Erbitux, perhaps influenced by all the financial shenanigans, this clearly shows that the drug is active," said Dr. Robert Mayer, head of gastrointestinal cancer at Boston's Dana-Farber Cancer Institute, who was not involved in the study.

Some other cancer specialists, however, said they found the latest study confusing and questioned whether it truly shows the drug's worth.

Whether ImClone now has enough scientific ammunition to push Erbitux onto the market remains to be seen, but spokesman Davit Pitts said they will ask the FDA's opinion on the latest data.

The sponsor of the new study, the German pharmaceutical firm Merck KGaA, said it will soon seek European approval to sell the drug and could have it on the market there by the end of the year. The company owns the rights to Erbitux outside of North America.

Merck & Co.

The new study was directed by Dr. David Cunningham of Royal Marsden Hospital in England, who presented the findings Sunday at a meeting in Chicago of the American Society of Clinical Oncology.

ImClone's former chief executive, Dr. Samuel Waksal, pleaded guilty to securities fraud and other charges and will be sentenced June 10. He tried to sell 80,000 shares of company stock and advised his daughter to unload her holdings before news of the FDA's unfavorable decision became public, sending the stock price down 77 percent. His friend, the home design celebrity Martha Stewart, is under investigation for her own sale of nearly 4,000 ImClone shares the day before the FDA announcement.

Erbitux is one of a new class of cancer medicines designed to work with pinpoint accuracy against the molecule-level defects that make the disease flourish. It is an antibody that jams up cancer's complex interplay of chemical growth signals.

In ImClone's initial study, Erbitux was tested on people with advanced colon cancer who had already failed to respond to irinotecan, a standard chemotherapy drug. Researchers believed that Erbitux could restore some of irinotecan's punch.

Usually, studies are designed to test an experimental drug against the standard medicines. But in this case, doctors reasoned that since the patients had already failed on irinotecan alone, any improvement with the combination could be attributed to Erbitux, so no comparison group was needed.

While the data showed that nearly a quarter of patients responded to the combination, the FDA turned back ImClone's application for approval, saying that Erbitux alone might have worked just as well. It also questioned whether all the patients had truly failed on chemotherapy.

The new study appears to address the FDA's questions. It was conducted on 329 colon cancer patients who had clearly failed to respond to irinotecan, based on strict definitions. They were given either Erbitux alone or in combination with irinotecan.

It found that 23 percent getting the combination and 11 percent taking Erbitux alone responded to treatment, meaning their tumors shrank by at least half. However, the effect was typically brief. Median survival was nearly nine months for those on the combination and seven months for patients getting only Erbitux.

"This supports much of the early clinical work," Cunningham said Sunday, showing that Erbitux "can resensitize cells to conventional chemotherapy."

Some doctors questioned the value of a drug study that fails to make a comparison with patients who are not getting the experimental medicine. Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, called the latest study "pretty confusing."

"You'd like to see a clear-cut comparison of two treatments," he said. "I don't know that this trial will provide the answer that people are looking for."

However, Dr. Bernard Ehmer, Merck's cancer chief, said it probably would have been unethical to give patients another round of chemotherapy, solely for comparison purposes, since they had already failed to respond and so had little chance of being helped.

The drug is now in larger studies against colon cancer as well as early testing for lung cancer.

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EDITOR'S NOTE: Medical Editor Daniel Q. Haney is a special correspondent for The Associated Press.

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Conference site: http://www.asco.org

medicine. Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, called the latest study "pretty confusing."

"You'd like to see a clear-cut comparison of two treatments," he said. "I don't know that this trial will provide the answer that people are looking for."

However, Dr. Bernard Ehmer, Merck's cancer chief, said it probably would have been unethical to give patients another round of chemotherapy, solely for comparison purposes, since they had already failed to respond and so had little chance of being helped.

The drug is now in larger studies against colon cancer as well as early testing for lung cancer.

------

EDITOR'S NOTE: Medical Editor Daniel Q. Haney is a special correspondent for The Associated Press.

------

On the Net:

Conference site: http://www.asco.org