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
For the Waksals, it all made sense. Their drug appeared to inhibit tumor growth, and when used with chemotherapy, which kills tumor cells, delivered a solid one-two punch. John Mendelsohn, president of the M. D. Anderson Cancer Center in Houston, who originally had discovered the drug, had seen good effects on animals: Erbitux, when combined with chemotherapy, brought remarkable results against tumors that resisted chemotherapy alone. Now, Study 9923 showed that 20 percent of people with colorectal cancer who did not respond to chemotherapy improved when they took the combination. In the world of cancer remedies, 20 percent is a big number. Perhaps the FDA would grant Erbitux accelerated drug approval, the Waksals thought; they requested a meeting.
But a problem loomed. The trial at hand with the 20 percent results, "Study 9923," was small, with only 120 patients. And it only had one arm--that is, there was no test to see whether patients given Erbitux alone would respond.
Since 1997, the FDA has had in place a "fast track" process for drugs, intended to treat a serious or life-threatening condition for which there is no other cure--and this process allows the FDA to accept data that are less robust than its normal gold standard. Still, not everyone at the FDA thought that Study 9923 met the FDA's basic standards. In an internal meeting before sitting down with ImClone, Susan Jerian, the primary FDA medical reviewer, made notes that reflected her view: Study 9923 did not "meet accelerated approval criteria." She did not think the small, one-armed study would provide enough data for the FDA to review. ImClone, however, did not know this.
A key meeting
On Aug. 11, 2000, team ImClone arrived at the FDA's Woodmont One building off a busy, mall-bedecked highway in Rockville, Md., and took seats along one side of a long conference table. They included Harlan Waksal; three other members of ImClone's regulatory and clinical team, one of whom was Michael Needle, who was in charge of the clinical trials; and five consultants, practicing oncologists involved in the trial. Among them was Leonard Saltz, a world-famous oncologist at Memorial Sloan-Kettering Cancer Center in New York and the developer of a chemotherapy regimen for colon cancer that bears his name. Saltz was the lead author of the 9923 study. Seated opposite them were Jerian, FDA reviewer Richard Steffen, and their supervisor, Patricia Keegan, from the FDA's Center for Biologics Evaluation and Research, along with eight other agency officials. Keegan's division, known as CBER, handles biotechnology products, where some believe the future of cures lies, but it had limited experience with drug approvals.
Keegan was impressed with Study 9923 and its 20 percent response rate. She asked how the FDA could be sure that patients would not have responded to continued chemotherapy treatment without the addition of Erbitux. The company said it had "pictures"--that is, it could provide scans to show how tumors grew under chemotherapy alone and then shrank when Erbitux was added. If that were the case, said Keegan, the study design was "probably acceptable" for fast-track consideration. ImClone went home happy.
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