(5 of 7)
This potential danger, when combined with the generally acknowledged risk of pph, was enough to persuade the FDA advisory committee to reject Redux by a 5-to-3 vote on the question of safety when it first came up for consideration a year ago. But a few hours later, FDA official Dr. James Bilstad reopened the discussion after some committee members had left the meeting. Since there was no longer a quorum, a new meeting was called for two months later, in November.
When that time came, however, the anti-Redux forces were missing. The meeting had been scheduled--all too conveniently, they suggest--to coincide with an international neurosciences conference in San Diego. And at the second meeting, Redux won approval by a one-vote margin. That, along with the fact that Interneuron sent a high-profile member of its board of directors, Alexander Haig, to the November meeting in what was perceived as a high-pressure lobbying effort, led to charges that Redux was moved through improperly.
Not so fast, counters the FDA's Bilstad. Yes, he did reopen the issue after last September's no vote. But that, he says, is because it became clear that the vote to reject was invalid: at least one member had misunderstood the wording of the question on the table. "Obviously," says Bilstad, "we wanted a nonambiguous recommendation from the committee." Some members had left the meeting, though, and without a quorum he couldn't proceed. He considered polling the absentees by phone, but the FDA counsel advised against doing so.
Hence the November meeting. Bilstad acknowledges that the schedule conflicted with the San Diego neurosciences conference. But since Seiden and other Redux opponents had thoroughly aired their views in September and had no new findings, Bilstad decided to go ahead. Says he: "We weighed the idea of putting off the decision for several months, until those experts could be there. Since the committee had heard their presentations before and were given transcripts, we decided that we had the benefit of their comments on the issues. It was a judgment call."
In fact, there is more than one way to interpret the neurotoxicity research. For one thing, observes Wurtman, animals don't necessarily respond to drugs the way humans do. The toxic dose of Redux in a monkey is only twice the therapeutic dose, but the therapeutic dose in a monkey is much higher to start with--as much as 10 times that of a human. It's therefore highly unlikely, he says, that a human user would OD.
Besides, says Bilstad, dexfenfluramine has been available in Europe for 10 years, with some 10 million users. "It is highly unlikely," he says, "that there is anything significant in toxicity to the drug that hasn't been picked up with this kind of experience."
The advisory committee's recommendation wasn't legally binding on FDA Commissioner David Kessler. Last December 22 neuroscientists, including Seiden and Dr. George Ricaurte of Johns Hopkins, asked the FDA to "forgo a final decision on dexfenfluramine until more information is available on its serotonin-neurotoxic potential in humans." Nevertheless, Kessler gave the go-ahead for Redux last spring.