Preterm birth remains one of the most urgent unresolved medical problems in obstetrics, yet only 2
therapeutics for preventing
preterm birth have ever been approved by the United States Food and Drug Administration, and neither remains on the market. The recent withdrawal of
17-hydroxyprogesterone caproate (17-OHPC, Makena) marks a new but familiar era for obstetrics with no Food and Drug Administration-approved
pharmaceuticals to address
preterm birth. The lack of
pharmaceuticals reflects a broad and ineffective pipeline hindered by extensive regulatory hurdles, soaring costs of performing
drug research, and concerns regarding adverse effects among a particularly vulnerable population. The pharmaceutical industry has historically limited investments in research for diseases with similarly small markets, such as
cystic fibrosis, given their rarity and diminished projected financial return. The Orphan Drug Act, however, incentivizes
drug development for "
orphan diseases", defined as affecting <200,000 people in the United States annually. Although the total number of
preterm births in the United States exceeds this threshold annually, the early subset of
preterm birth (<34 weeks' gestation) would qualify, which is predominantly caused by
inflammation and
infection. The scientific rationale for classifying
preterm birth into early and late subsets is strong given that their etiologies differ, and
therapeutics that may be efficacious for one subset may not work for the other. For example, antiinflammatory
therapeutics would be expected to be highly effective for early but not late
preterm birth. A robust therapeutic pipeline of antiinflammatory drugs already exists, which could be used to target spontaneous early
preterm birth, in combination with
antibiotics shown to sterilize the amniotic cavity. New applications for
therapeutics targeting spontaneous early
preterm birth could categorize as
orphan disease drugs, which could revitalize the
preterm birth therapeutic pipeline. Herein, we describe why drugs targeting early
preterm birth should qualify for orphan status, which may increase
pharmaceutical interest for this vitally important obstetrical condition.