COMPANY WITHDRAWS AIDS DRUG APPLICATION
By Paul Recer
AP 22 March 2002
Washington -- Problems which federal officials said were
"potentially quite serious" prompted the withdrawal of an application for
approval to allow pregnant women and newborn babies to take an
existing AIDS drug.
Boehringer Ingelheim Pharmaceuticals Inc. of Ridgefield, Conn.,
announced Friday that it was withdrawing the application. It had asked
the Food and Drug Administration to approve the
drug nevirapine for preventing mother-to-child HIV transmission.
John Wecker of Boehringer said that the decision came after
researchers at the National Institute of Allergy and Infectious Diseases
audited a 1999 clinical trial conducted in Uganda for
the NIAID by Johns Hopkins University researchers.
The audit raised questions about documents and records supporting the
study results, Wecker said. They were published in the British journal
"The NIH (National Institutes of Health conducted
an audit and the FDA called the three parties together to discuss it,"
Wecker said. "We agreed to withdraw the application. Once the issues
are resolved, we intend to resubmit."
The 1999 study concluded that nevirapine was more effective than
another drug in preventing pregnant women from passing HIV infection
to their babies during birth and nursing.
Wecker said the audit uncovered "no reason to suspect that there was a
problem with the fundamental conclusions."
However, Jason Brodsky, an FDA spokesman, said there are problems
with the study that "the agency believes are potentially quite serious."
Brodsky declined to identify the problems, but said the FDA is not
recommending any change in the approved uses of nevirapine. The drug,
marketed under the name Viramune, is approved in the U.S. to treat
HIV in adults and in children over the age of two.
Nevirapine continues to be used in dozens of other countries by
pregnant women and newborns.
Dr. John R. LaMontagne of the NIAID, the NIH agency that paid for
the Uganda study, said that the problems mostly are in record keeping.
He said there are differences in the way hospitals in Uganda keep
records and the requirements of the FDA.
"There is no question about the validity of the Lancet study,"
LaMontagne said. "The problems are in the rather arcane requirements
in record keeping."
He said the FDA "quite rightly has a rigorous standard" and that there
were problems meeting this standard in a study conducted in Uganda.
The Hopkins researchers meticulously gathered data for the study using
a system of "shadow records," which are separate copies of the records
kept by the Ugandan hospital, LaMontagne said. The FDA requires that
a drug application include the original records for the patients.
The FDA also requires that any "serious adverse event" experienced by
a patient during a drug trial be reported in data submitted to the agency.
Adverse events are illnesses or other health-related incidents that occur
while a patient is on the test drug.
LaMontagne said there often were differences of opinion between the
Hopkins researchers and the Uganda hospital staff of what constituted a
"serious adverse event." He called it "professional differences of
"The FDA wants us to cross-match our patient charts against the
hospital records," LaMontagne said. "The FDA is right in doing this. It is
an important safeguard."
Dr. Peter Lurie of Public Citizen Health Research Group, a watchdog
group that monitors federal health policies, said it is up to the
researchers to maintain records that meet the strict FDA standards.
The FDA requires that data from drug trials, no matter where in the
world the studies are conducted, must meet the same standard.
Otherwise, they cannot be used to evaluate a drug for approved use in
this country, Brodsky said.
The pharmaceutical company continues to donate nevirapine to
programs in some 23 countries where the drug is used to help prevent
mother-to-child HIV transmission, Wecker said.