The Drug That Could Have Been
When a young company called ImClone said it had a hot new cancer drug, its stock leapt on the bet that it would get an OK from the FDA. Now the stock has tanked, ImClone's charismatic CEO is indicted, and, Martha Stewart is in trouble, too. But the big losers are cancer victims. Here's the real story behind ImClone and why it failed to win the FDA's approval
That was Keegan's call. But Jerian says she was not convinced that the study was good enough for FDA purposes. Richard Pazdur, the director of oncology review in the FDA's more experienced Center for Drug Evaluation and Research, says that relying on Study 9923 put the drug in jeopardy of being rejected. For starters, the Waksals presented backup animal studies to show that the drug worked best in combination. That was "a very risky venture," Pazdur said, because human studies can bring different results. ImClone's human study, 9923, did not even test whether Erbitux worked alone. That was important, because chemotherapy is toxic; perhaps patients could take Erbitux alone and avoid chemotherapy. The company needed to do a randomized trial looking at the combination of chemotherapy with Erbitux versus Erbitux alone, Pazdur says. "That would be the correct way of developing this drug."
By January, Keegan's team had come to the same conclusion. So one week after informing the company that Erbitux had been accepted for fast-track review, the FDA sent a letter requesting the additional randomized study. The company was floored. On January 26, a conference call was held with Keegan, her reviewers, and ImClone. According to minutes recorded from the call that were obtained by U.S. News, ImClone protested. It would be "unethical" to conduct a large study of Erbitux alone, the company said, because it believed the drug would not work for sick patients.
In addition, the company said it had left the Aug. 11, 2000, meeting with the understanding that only Study 9923 would be needed. "As there was no discussion regarding the need to supply data for [Erbitux alone] . . . ImClone has not pursued" that kind of trial, the company said. It had planned to study Erbitux alone later, in follow-up trials. FDA members now say that they raised the issue of whether Erbitux would work by itself at the August meeting, but meeting minutes do not reflect that discussion.
By the end of the call, the two sides had come to a compromise: ImClone would conduct a small study, in 20 to 50 patients, using Erbitux alone. Pazdur is now critical of that decision. "In order for that to work, you had to have a 0 percent [effectiveness] almost in the single agent Erbitux study," he says. "So in essence they were betting against their own drug to get that combination approved."
On March 27, Harlan Waksal, Leonard Saltz, and John Mendelsohn marched back into the FDA's Woodmont One building for a second face-to-face meeting. They argued over the second study of Erbitux, according to meeting minutes, with the FDA telling the company it wanted the study to be part of the official application and the company complaining that this was a late request by the agency. They then talked about other elements of the application, and ImClone began enrolling patients for the second study on April 1.
Pressure mounts
On the afternoon of Saturday, May 12, 2001, Leonard Saltz stood on stage in a huge convention hall at the American Society of Clinical Oncology conference in San Francisco. His face, beaming, was captured on several large projection screens. Saltz had big news: Erbitux, he said, used in conjunction with chemotherapy shrank tumors in 22.5 percent of colon cancer patients for whom other treatments had failed. The results were "knock-your-socks-off exciting," Saltz told the crowd. In the room were not just cancer physicians but also scores of investors looking for the next blockbuster. Wall Street analysts coming to the meeting expecting good news got what they were looking for.
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