A leading US professor of obstetrics claims the US FDA’s ‘adversarial’ stance over the licensing of new drugs in obstetrics and other specialist fields is causing frustration among patients, physicians and drug developers.
Speaking at the 3rd International Preterm Labour Congress in Montreux, Switzerland, Thomas Murphy Goodwin, professor of the division of maternal fetal medicine at University of Southern California, said the FDA was hindering rather than facilitating progress in introducing new therapies for unmet needs and that “numerous other commentators are also calling for the agency to demonstrate an increase in collegiality."
There’s a big emphasis on getting the FDA to fulfil its mandate to co-operate with patients, investigators and pharmaceutical companies in helping to bring new drugs to market rather than acting as gatekeeper, he said.
Its attitude is hindering drug development for conditions in smaller specialties such as obstetrics and paediatrics because these depend on a worldwide marketplace to make products viable, he suggested.
US obstetricians have no access to tocolytic therapy - drugs proven to halt pre-term labour - because the FDA is insisting on trials that are impossible to conduct before it will consider licensing them, explained Prof Murphy Goodwin. “There have been no new developments in pre-term labour in the USA for 40 years.”
He said the tocolytic agent Tractocile (atosiban) has been approved for use in Europe following comparator studies where it proved significantly safer and more effective than other drugs commonly used to try and arrest pre-term labour such as beta agonists, calcium antagonists or magnesium sulphate. However the FDA would not consider approving Tractocile until it has been studied against placebo or approved comparator drugs in US patients.
“This is a Catch 22 situation - an impossible demand to fulfil - because we don’t have a single approved tocolytic drug available in the US and placebo is unacceptable to most people,” he pointed out.
Drugs for other conditions are used off-label to try and delay pre-term labour, but despite doubts about their efficacy,and their associated side-effects, neither women nor physicians were comfortable with having access only to placebo as an alternative to Tractocile in a randomised trial.
“In the US, even if the president’s daughter goes into labour early she could only be treated with a drug that is not labelled, has been investigated in only a few hundred patients and in studies that suggest it doesn’t work.”
Only six of 175 centres polled said they would consider participating in a placebo-controlled trial, he added. “During attempts to conduct placebo-controlled trials in Canada, physicians wouldn’t even wait one hour before abandoning the perceived placebo." After three years they had recruited only 158 of the minimum 600 patients needed.
Ferring Pharmaceuticals' obstetrics medical director Dirk Schneider said the company is not currently seeking US approval for Tractocile because it considers placebo-controlled trials “unethical."
Companies are being asked not only to supply placebo-controlled data but also to follow babies’ development for years to provide all kinds of outcome data, added Prof Murphy Goodwin.
The FDA has been saying for the past eight months that it will hold a summit meeting where pharmaceutical companies, patient advocates and investigators can sit down and discuss the issues, he said. As yet no date has been fixed.
“Meanwhile, research is piling up in a regulatory bottleneck and pharma companies with drugs in development are waiting for someone to break the log jam.”
From Olwen Glynn Owen in Montreux
