28 June 1997
THIS WEEK

Secrecy row over slimmer's drug
Kurt Kleiner, Washington DC

THE US government's drug regulator is under fire over the way it is
investigating claims that a popular dieting drug can cause brain damage.
Some of the US's top neurotoxicologists are accusing the Food and
Drug Administration (FDA) of placing commercial secrecy above
public safety.
Dexfenfluramine, which is marketed as Redux, was approved
by the FDA last year. It boosts the brain's levels of serotonina
neurotransmitter that helps regulate appetite, mood and other
behaviours. Redux is a refined version of an older drug called
fenfluramine. Unlike fenfluramine it contains just one of the two
mirrorimage forms of the active molecule, which makes it less likely to
cause drowsiness.
Animal studies have suggested that fenfluramine and Redux
can damage serotoninproducing neurons at doses as low as twice those
needed to cause weight loss (This Week, 14 December 1996, p 8).
Because the damage can only be confirmed when the brain is dissected,
it is unclear whether this happens in people.
But given these concerns, the FDA attached a condition to its
approval for Redux, demanding that WyethAyerst Laboratories of
Philadelphia, the company which markets Redux, conduct a followup
study to check for signs of damage in
slimmers who are taking the drug.
In February, FDA officials met representatives of WyethAyerst
along with five independent scientists to discuss the design for the trial.
But none of the scientists who had raised the warnings about Redux was
invited, and many of them are now up in arms. Neither the company
nor the FDA have revealed details of the planned trial.
"We question whether a closed meeting is in keeping with the
FDA's mission,"
writes Lewis Seiden, a pharmacologist at the University of Chicago, in a
letter to acting FDA commissioner Michael Friedman. "We cannot see
any circumstances concerning safety where proprietary and commercial
interests of an individual corporation can be more important than the
public interest."
Any brain damage caused by Redux is likely to be subtle and
difficult to detect says George Ricaurte of Johns Hopkins University in
Baltimore. This makes it vital that neurotoxicologists who have studied
Redux should be consulted before designing a safety trial, he says. It
would be easy to design a study that would seem to prove the drug
safe, even if it is not, says Ricaurte. "The people they brought in,
although experts in their own fields, are not experts in fenfluramine and
its neurotoxic potential."
One of the five independent scientists brought in by the FDA
Emil Coccaro, a psychiatrist at the Medical College of Pennsylvania in
Philadelphiawas paid by WyethAyerst to attend a twoday FDA
review of Redux in 1995. However Coccaro says he has no ongoing
relationship with the company, and denies that he has a conflict of
interest.
In his letter, Seiden demands an open meeting to review the
planned trial. But the FDA has no plans for such a meeting. Don
McLearn, an FDA spokesman, says it is usual practice to restrict access
to meetings at which proprietary information is discussed.