Call for "best pharma for pregnant mothers" act

Preterm births (those before 37 weeks of pregnancy) account for more than one in 10 births worldwide, and the number is rising. But many doctors are treating such patients with the same drugs introduced some 40 years ago.

The difficulties of testing drugs on pregnant women means that a new and better class of drugs, known as tocolytics, is failing to get approval. It is an issue that experts in preterm labour were invited to discuss at a Ferring-sponsored congress in Geneva in April.

Preterm births can create severe developmental problems in babies. There are two main aims in the management of preterm labour: first, to delay delivery for long enough (usually 48hrs) to allow doctors to give corticosteroids to the mother to help speed up the development of the baby's lungs; and second, to permit the transfer of the mother and unborn baby to a specialist care unit.

Tocolytics are a relatively new class of drugs used to stop the uterine contractions of preterm labour and thereby delay premature birth. There are, however, a number of ethical difficulties in studying these drugs in pregnant women and contrasting approaches for their evaluation by the FDA and the EMEA.

At the Geneva congress, T Murphy Goodwin, professor and chief of Maternal-Fetal Medicine, University of Southern California, said: "Studying a medication for two patients (mother and baby) and consenting women for study in the midst of labour make tocolytic trials uniquely complex. There is an urgent need for co-operation between regulatory agencies, investigators and industry to decide on the best methods for studying and approving tocolytic medications."

One such tocolytic, Atosiban, was approved in the EU through comparative tests with a drug already on the market. But there is no comparator drug available on the US market to test against, said Professor Goodwin. Placebo trials are required by the FDA, but drug companies find it virtually impossible to enroll enough patients to make the trial viable, and even when trials are attempted it is difficult to prove efficacy in a way that satisfies the regulatory bodies.

A new clinical practice evaluation in preterm labour management in six European countries on the tocolytic Tractocile (atosiban), developed by Ferring, showed that it delayed premature birth and reduced the need for an alternative tocolytic compared with usual care.

The European, prospective, open-label, randomised clinical trial involved 811 women in 105 centres in Austria, France, Germany, Italy, Spain and the UK. The study set out to compare the efficacy of Tractocile with usual care (b-agonists, alone or with magnesium, calcium channel blockers and bed rest) in threatened preterm labour, to evaluate the efficacy and safety of early administration of Tractocile and to describe treatment administration patterns of tocolytics in usual care.

"Atosiban was statistically more efficacious than usual care when assessed using our primary efficacy endpoint of the proportion of women remaining undelivered and not requiring an alternative tocolytic at 48 hours," said professor Husslein. "Our study confirms both the efficacy and safety of atosiban previously demonstrated in registration trials."

Despite these results the drug has yet to be approved in the US. Ferring is in talks with the FDA over the issue of approvals. It would like to see a "Best pharma for pregnant mothers" act introduced in future, just as the FDA has a "Best pharma for children" act.