Advancing drug development for the prevention of spontaneous preterm birth

Abstract

In the United States, one in 10 pregnancies results in preterm birth (PTB), making it the leading cause of infant morbidity and mortality. Following the 2023 withdrawal of Makena (hydroxy progesterone caproate) for lack of efficacy, clinicians currently lack FDA-approved options for women at risk of recurrent spontaneous PTB. Researchers and pharmaceutical companies may be hesitant to commit resources to develop therapies for PTB. This report summarizes a Food and Drug Administration–Duke Margolis Institute for Health Policy public workshop held in January 2024 to discuss challenges and opportunities for advancing drug development for the prevention of PTB. Participants—researchers, clinicians, industry representatives, families, and regulators—highlighted challenges that hinder the development of PTB therapies, including the limited understanding of PTB causes, ethical concerns for trials, and lack of consensus on appropriate outcome measures. A few of the emerging recommendations suggest that supporting basic science research to address knowledge gaps, such as elucidating the biological drivers and underlying mechanisms of spontaneous preterm birth (sPTB), as well as improving data quality and evidence and focusing on gestational age-specific clinical outcome endpoints could help move the needle forward in this area. Meeting participants also shared perspectives on research priorities, discussed optimizing study design for dose-finding, and strategized about funding and investments. Key recommendations included pursuing greater regulatory flexibility, innovative trial designs, expanding federal and philanthropic funding incentives to de-risk early-stage development, and strengthening data-sharing and research collaborations to accelerate translation of discoveries into therapies.

Keywords

FDA public meeting spontaneous preterm birth spontaneous preterm birth ethics spontaneous preterm birth prevention spontaneous preterm birth research US Food and Drug Administration

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References

World Health Organization . Preterm birth. WHO, 2023. https://www.who.int/news-room/fact-sheets/detail/preterm-birth (Accessed September 24, 2024).

Martin

Osterman

MJK

. Shifts in the distribution of births by gestational age: united States, 2014–2022. Natl Vital Stat Rep 2024; 73(1): 1–11.

Martin

Osterman

MJK

. Shifts in the distribution of births by gestational age: united States, 2014–2022. Natl Vital Stat Rep 2024; 73(1): 1–11.

4. March of Dimes . Prematurity profile: united States. March of Dimes, 2022. https://www.marchofdimes.org/peristats/assets/s3/reports/prematurity/PrematurityProfile-UnitedStates.pdf (Accessed September 24, 2024).

Meis

Klebanoff

Thom

, et al. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med 2003; 348(24): 2379–2385.

Baxter

Crary

Coler

, et al. Addressing a broken drug pipeline for preterm birth: why early preterm birth is an orphan disease. Am J Obstet Gynecol 2023; 229(6): 647–655.

American College of Obstetricians and Gynecologists . Prediction and prevention of spontaneous preterm birth. ACOG Practice Bulletin 2021. https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2021/08/prediction-and-prevention-of-spontaneous-preterm-birth (Accessed September 24, 2024).

Waitzman

Jalali

Grosse

. Preterm birth lifetime costs in the United States in 2016: an update. Semin Perinatol 2021; 45(3): 151390.

National Academies of Sciences, Engineering, and Medicine . Advancing clinical research with pregnant and lactating populations: overcoming real and perceived liability risks. The National Academies Press, 2024.