Addressing a broken drug pipeline for preterm birth: why early preterm birth is an orphan disease

• Published in: American journal of obstetrics and gynecology 2023-12, Vol.229 (6), p.647-655
• Main Authors: Baxter, Carly, Crary, Isabelle, Coler, Brahm, Marcell, Lauren, Huebner, Emily M., Rutz, Sara, Adams Waldorf, Kristina M.
• Format: Article
• Language: English
• Subjects: 17 alpha-Hydroxyprogesterone Caproate - therapeutic use; bronchopulmonary dysplasia; Female; fetus; Humans; Hydroxyprogesterones - therapeutic use; Infant, Newborn; intraventricular hemorrhage; neonate; orphan disease; orphan drug; Pharmaceutical Preparations; Pregnancy; Premature Birth - drug therapy; Premature Birth - prevention & control; prematurity; preterm birth; preterm labor; Rare Diseases - drug therapy; therapeutic; tocolytic; United States
• ISSN: 0002-9378; 1097-6868; 1097-6868
• DOI: 10.1016/j.ajog.2023.07.042

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