Yesterday, while I was presenting a talk on preterm birth (PTB) to a large family practice group and their 29 residents who practice obstetrics, an FDA advisory panel was reviewing an application from Adeza Biomedical Corporation to bring the drug Gestiva® to market for the prevention of preterm labor. Gestiva® is a compounded formulation of a synthetic progesterone (17-?-hydroxyprogesterone caproate) in oil, now affectionately referred to as "17-P," that is administered by intramuscular injection on a weekly basis and has been shown in one clinical trial (Meis P, et al., NEJM. 2003; 348:2379-85) to reduce by about one-third the risk of preterm labor and delivery in a population of women who had delivered prematurely in the past. If the FDA grants final approval for this to Adeza, they will become the exclusive distributors of this compound, an issue I will return to later in this post.
Before I knew about the FDA meeting, I had already decided to write a series of posts on preterm labor. It is a BIG problem in this country, and unfortunately, it is a growing problem. In 1972, the incidence of PTB (delivery less than 37 weeks') was 7-8%. By 2003 this rate approached 13% of all deliveries and was as high as 15-17% in certain lower socioeconomic groups. To put this in perspective, of the 4 million deliveries that year, almost 500,000 were premature. This means that on an average day in the U.S., 1300 babies are born too early and of these more than 200 are considered to be very preterm (less than 32 weeks'). Prematurity, rather than birth defects, is now the leading cause of neonatal mortality in this country, accounting for 25% of infant deaths during the first month of life.
In 2002, PTB accounted for more than 45% of all healthcare spending for infants ($15.5 billion)! The average cost of a hospital stay for a preterm baby was $79,000 compared to $1,500 for a normal term delivery. It is important to understand that this represents just the initial costs to the healthcare system. With advances that have been made in neonatal intensive care, now more than 90% of infants born weighing less than 1500 g survive. However, more than 50% of very low birthweight infants, weighing less than 1000 g, have disabilities by 30 months' of age. Overall, preterm delivery is associated annually with more than 100,000 casese of severe disability, including cerebral palsy, mental retardation, vision and hearing impairment, and chronic lung diseaese. These chronic conditions add multiples to the initial cost of care for these infants across their lifetimes.
In my next posts, I will discuss risk factors associated with preterm birth, diagnosis of preterm labor, and management algorithms. But before I conclude today, I did want to return to the Gestiva® story mentioned in the first paragraph. Very few drugs have been “approved for use in pregnancy” by the FDA over the years. Based on the clinical trial referenced above, it appears Gestiva® has the potential to reduce preterm deliveries, or perhaps lengthen pregnancy, in women at high risk for recurrence of PTB. Funny thing is that we used a 17-P compound many years ago for the same indication, even though we did not have good clinical studies to support its efficacy and safety. That drug, Delalutin®, was produced by Bristol-Myers Squibb Co. and was never FDA-approved for use in pregnancy. It was removed from the market in 2000 for no reason to my knowledge other than that no one used it for anything anymore. Once efficacy of 17-P was shown, several compounding pharmacies around the country began producing and distributing the drug for use in preterm labor prophylaxis. It is my understanding that these pharmacies obtained the active ingredient (17-P) from Adeza.
When it became clear that there might be a market for 17-P, Adeza jumped in and filed the application that would restrict production of the compound to their own facilities. Most of us predict that the FDA will approve the application with the admonition to Adeza that careful long-term studies of safety are done on both pregnant women and the babies exposed to the drug during pregnancy. Although no significant risks of 17-P were reported over almost 50 years' of use, no methodical clinical trials were ever performed to document its safety in pregnancy either. With FDA approval will most certainly come a two- to four-fold increase in cost (currently between $100-200 for a course of therapy), probably, with very little improvement in quality over that which is now available from the compounding pharmacies. Hopefully, this will not put the drug outside the expense that can be borne by patients themselves, many of whom will be from lower socioeconomic risk groups, or the third party payers (especially Medicaid) for its indicated use.
Use of 17-P will be no panacea for the problem of PTB because preterm labor is a symptom and not a disease that is going to require concentrated, multidisciplinary, social, as well as medical, intervention if we are to achieve a significant reduction in rates. However, this is one problem in which every little bit helps. When I was medical director at the East Tennessee Regional Perinatal Center, I used to tell our residents that if we could prevent just 1 or 2 preterm deliveries at 24-26 weeks' annually, we could fund the entire program for another year with the savings. At the least I would hope that any furor over the marketing of 17-P translates into enhanced public awareness of the problem of PTB and, perhaps, "grass-roots" activism among women for support of programs that might eventually have a real impact on this problem.