A tale of greed, bad science and poor decision-making by the FDA which is unfortunately not unique.
Pre-term birth, delivery before 37 weeks gestation, is a serious problem. It puts the baby at risk of disability or even death. Women who have had one “premie” are eager to do anything to avoid one in subsequent pregnancies, as are their doctors. The best estimates are that women who have had one premature delivery have a 30% risk of having one on a subsequent pregnancy.
Short of putting women on prolonged bedrest, there has been little available to reduce the rate of premature delivery. A “meta-analysis” of previously published studies done in 1990 suggested that while the hormone hydroxyprogesterone did not prevent miscarriage (for which it had been used), it appeared to protect against preterm birth. In 2003, a trial was conducted that claimed to show that injecting pregnant women weekly with hydroxyprogesterone in mid-pregnancy reduced the number of premature births. The treated group had 36% premature deliveries compared to 55% in the placebo group. There were many critics of the study, who pointed out that the placebo group had a much higher rate of premature birth than would have been expected, and those in the treated group had a similar but higher rate than expected if nothing were done. It was also pointed out that the pregnant uterus was “awash” in progesterone and so there was little biologic reason to expect the injections to do much.
Despite these reservations, many obstetricians began prescribing this treatment. Compounding pharmacies began making the injections and selling them for $15/shot. Enter stage right Adeza Biomedical, which used the 2003 trial to support their application for FDA approval of their branded hydroxyprogesterone for the prevention of premature birth. Many of the FDA’s own scientists pointed out the flaws of the trial, and when the branded product (Makena) was approved, it was with the stipulation that further trials be conducted. This trial, which enrolled over three times as many women, and reported results in March 2019, showed NO benefit from use of Makena.
The FDA convened another “expert panel” to decide if the drug should be kept on the market. The panel voted unanimously that the newer trial did not verify the benefit of Makena, and 13 to 3 that the combined evidence from the original and the newer trial did not provide evidence of any substantial benefit. When the vote came on whether to leave it on the market, the vote was much closer: 9 to 7 in favor of removing it from the market. The FDA decided to leave it on the market.
“Follow the money” has clarified many apparently confusing stories. While the product was sold for $15/shot by compounding pharmacies, Makena was marketed at an initial price of $1440/shot! As generics have entered the market, the list price has fallen, but is still $848/shot for a product that was profitable at $15. This obscene profit margin has allowed its current manufacturer, AMAG Pharmaceuticals, to generously support the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine, which supplied many of the expert panelists. Neither society has yet reflected the negative trial in their guidelines.
My take home is that all FDA panelists should be truly disinterested. Societies accepting money from drug manufacturers and researchers getting support from manufacturers should be automatically excluded from advisory panels.
Prescription for Bankruptcy. Buy the book on Amazon