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
But the FDA was struggling. Two new reviewers, George Mills and Lee Pai-Scherf, had arrived on the scene. They saw that some patients' CT scans were missing, that patients who weren't eligible were in the trial, and patients were being given varying doses of chemotherapy--all skewing the results. James Abbruzzese, the chairman of the gastrointestinal medical oncology department at M. D. Anderson, says he warned the company about this problem. "The writing [in the protocol] was not precise," he says. He says he had an E-mail exchange with ImClone over the issue and that after he raised objections, the E-mail "just stopped." M. D. Anderson declined to participate in the trial. One investigator who did work on the trial saw another flaw: Because of media attention, patients were "calling from all over the country begging for it." Perhaps, this investigator said, doctors felt compelled to relax eligibility rules so desperate patients could get the drug.
By November 30, before the results of the Erbitux-only study were even submitted, the FDA's reviewers had decided to recommend what the FDA calls a "refusal to file" letter. Keegan would later concur. By not accepting the drug's application, its approval would be stalled, maybe for years. At this point, however, ImClone knew only that the FDA saw some problems in its study, problems its vice president for regulatory affairs, Lily Lee, had promised to remedy. So on December 4, ImClone turned in the results of its Erbitux-only study. Now it was the FDA's turn to be floored. The study showed the drug shrank tumors in six of the 57 patients, more than 10 percent. Ten percent is noteworthy--thus the study suddenly threw into question whether the Erbitux-chemotherapy combination was needed. Maybe Erbitux worked well enough by itself!
Keegan had had enough. She had trusted the company, believing that it would show that Erbitux worked only with chemotherapy. "I felt misled personally," she said. ImClone, however, didn't see the problem. Why not approve Erbitux for combination use, and continue studies to see if could also be used alone? Still, the company appreciated the FDA's position at this point: The agency felt it had been fooled.
Breakdown
On December 4, ImClone's Vice President Lee hopped a train from New Jersey to make a surprise visit to FDA headquarters. She was worried about the application. The FDA, however, was noncommittal. All options were open, reviewers Mills and Pai-Scherf told Lee: ImClone could submit additional information, or the company could withdraw it. The FDA could accept the application or refuse to accept it. Mills presented the options but was careful not to put extra weight on any one of them. Although both reviewers say that Lee asked whether the FDA would refuse the application, she was not given an answer.
Eight days later, the agency teleconferenced with ImClone and Bristol-Myers Squibb. It was an ominous discussion, but still the agency did not reveal that it had made a decision. By December 20, however, when ImClone called to ask about the status of Erbitux, the agency told the company not to make contact again. "We were informed at the time that a decision had been made and that it would be coming sometime in the next week," Harlan Waksal told a congressional committee. Bristol-Myers, frantic, asked a consultant lawyer to find out what was happening at the FDA. On December 24, Sam Turner of Bennett, Turner & Coleman called the FDA's Pazdur, who told him that the refusal-to-file letter was coming. Sam Waksal called friends at the agency but could not find someone to intervene. On December 28, at 2:55 p.m., the FDA faxed the refusal-to-file letter to ImClone. In the two days before the letter arrived, Waksal's daughter Aliza, his father, and Martha Stewart unloaded ImClone stock worth, respectively, $2.5 million, $8 million, and $227,000. Sam Waksal's indictment charges that he had unsuccessfully tried to dump $4.9 million worth himself and that he had tipped others off. He has pleaded not guilty; a plea bargain is still possible, sources say. Stewart, meanwhile, is under investigation for insider trading and making false statements about her stock sale.
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