WASHINGTON -- Despite outspoken misgivings by advisorycommittee members, FDA Commissioner David Kessler onTuesday proclaimed that new ground had been broken by thepanel's decision to recommend approval of the AIDS drug ddCunder the agency's new accelerated approval regulations.
The regulations allow market approval for a therapy if it is"reliably based on evidence of the drug's effect on a surrogateend point that reasonably suggests clinical benefit," on thecondition that studies are completed that establish and definethe degree of clinical benefits.
"The usefulness of that whole concept was at issue today,"Kessler said. The ddC recommendation "was an affirmation thatthe concept is worth trying" and that the surrogate end pointdata used by the committee "fit what the new policy wasintended to encompass," he said.
On Monday, the committee confirmed its interimrecommendation of another AIDS drug, ddI, which had beenbased on surrogate data.
The FDA published its regulations in the Federal Register lastweek. Although they must undergo a public comment periodbefore final approval, "I think that is only a technicality,"Kessler told the meeting. "We stood ready to act on ddI lastyear without the regulation, and we stand ready to invokeapproval (of ddC) if the committee so recommends."
The regulations represent a change in the way of thinking forthe committee, Kessler said. "We are trying to provide anoption for you to recognize that you can take a risk -- that youcan be wrong," he told the panel. "The basis of this is awillingness to say up front, 'We may be wrong down the road,but that's OK because we are going to require follow-up(clinical end points study data) and make a midcoursecorrection, if necessary.'"
Kessler said, "The whole point is to relieve some of the handwringing, some of the angst" by committee members. But asthey deliberated, committee members continued to expressmisgivings.
In the committee's deliberations on Monday, Theodore Eickhoff,director of internal medicine at Presbyterian-St. Luke's MedicalCenter in Denver, noted "a litany of discomfort going aroundthe table. It seems astonishing that this is the same group thatmade that vote (to recommend approval of ddI) last summer."
Members continued to express their discomfort on Tuesday."We are really moving here at lightning speed, but all of us aredragging our heels as we move forward," said Deborah Cotton,assistant professor of medicine in the Department of HealthPolicy and Management at the Harvard School of Public Health,after the ddC vote. "I am uneasy about having codification ofwhat sounds to me like an experiment," she said.
"I am frankly skeptical that we will ever get the data thatspeak directly to these indications," said committee memberMark Smith, vice president of the Henry J. Kaiser Foundation inMenlo Park, Calif. "I am troubled by the way we are beingmanipulated and exploited (by the FDA based on) the dare that,'We are doing this anyway, so you have to let us continue to doit.' "
Paul Meier, chairman of the departments of Infectious Diseasesand Microbiology at the University of Pittsburgh GraduateSchool of Public Health, said the committee's approvals of ddIand ddC may send a "dreadful" message to industry that itshould submit surrogate end point data to the FDA without longfollow-up studies and "take your chances."
Kessler assured committee members that the new regulationsprovide a streamlined procedure for withdrawing anaccelerated product from the market if the sponsor fails toreturn with evidence of clinical benefit.
"The absence of showing clinical benefit in a reasonable amountof time would be tantamount to no data," said Kessler. "This isonly going to work if we have the resolve to put the genie backin the box, but I think that is the road we are going down."
-- Kris Herbst BioWorld Washington Bureau
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