Preterm birth and 17OHP–why FDA should not withdraw approval

Regulators are considering rescinding approval of 17 alpha-hydroxyprogesterone caproate (17OHP), which is indicated for prevention of recurrent premature birth, but observers warn that they must tread carefully. Michael F. Greene, MD, with Massachusetts General Hospital, Mark A. Klebanoff, MD, MPH, of Nationwide Children’s Hospital, and David Harrington, PhD, of Harvard School of Public Health acknowledge some legitimacy for the recommendation from FDA’s Center for Drug Evaluation and Research. 17OHP received expedited approval based on premarket research showing a 34% relative risk reduction for recurrent preterm birth at less than 37 weeks and a reasonable expectation that this result would subsequently reduce neonatal morbidity and mortality. Postmarket trial data, however, suggested not only a smaller reduction in risk but also the possibility of up to a 26% increase in risk. Despite the misalignment between the studies, Greene, Klebanoff, and Harrington say regulators cannot ignore differences in the respective trial populations. Black women, who are disproportionately affected by recurrent preterm birth, were significantly underrepresented in the newer study. The authors fear that withdrawing approval of 17OHP would leave this at-high-risk population with zero therapeutic options for preventing this devastating complication. “When the majority of a population achieves little benefit from a drug, but a minority demographic group at greatest risk for a serious medical problem appears to obtain significant benefit, any decision that will ultimately make it impossible to obtain the drug should be undertaken cautiously,” Greene, Klebanoff, and Harrington conclude. “This issue is particularly pressing when that minority group may be the least able to find and financially afford work-arounds to obtain the needed medication in our complex medical system that has a history of failing to serve them well.”