New medicines for spontaneous preterm birth prevention and preterm labour management: landscape analysis of the medicine development pipeline

Abstract

Background: There are few medicines in clinical use for managing preterm labor or preventing spontaneous preterm birth from occurring. We previously developed two target product profiles (TPPs) for medicines to prevent spontaneous preterm birth and manage preterm labor. The objectives of this study were to 1) analyse the research and development pipeline of medicines for preterm birth and 2) compare these medicines to target product profiles for spontaneous preterm birth to identify the most promising candidates.

Methods: Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched to identify candidate medicines (including drugs, dietary supplements and biologics) and populate the Accelerating Innovations for Mothers (AIM) database. This database was screened for all candidates that have been investigated for preterm birth. Candidates in clinical development were ranked against criteria from TPPs, and classified as high, medium or low potential. Preclinical candidates were categorised by product type, archetype and medicine subclass.

Results: The AIM database identified 178 candidates. Of the 71 candidates in clinical development, ten were deemed high potential (Prevention: Omega-3 fatty acid, aspirin, vaginal progesterone, oral progesterone, L-arginine, and selenium; Treatment: nicorandil, isosorbide dinitrate, nicardipine and celecoxib) and seven were medium potential (Prevention: pravastatin and lactoferrin; Treatment: glyceryl trinitrate, retosiban, relcovaptan, human chorionic gonadotropin and Bryophyllum pinnatum extract). 107 candidates were in preclinical development.

Conclusions: This analysis provides a drug-agnostic approach to assessing the potential of candidate medicines for spontaneous preterm birth. Research should be prioritised for high-potential candidates that are most likely to meet the real world needs of women, babies, and health care professionals.

Keywords: Aspirin; Celecoxib; Drug development; Isosorbide dinitrate; L-arginine; Nicardipine; Nicorandil; Omega-3 fatty acid; Oral progesterone; Preterm labour; Selenium; Tocolytics; Vaginal progesterone.

Fig. 1

Details of the candidates in the R&D pipeline for preterm birth/labor. Summary of the 178 candidates in the R&D pipeline for the prevention of preterm birth and management of preterm labor from 2000 – 2021. The proportion of candidates A in active development, and inactive (no publications since 2018), B in each phase of the development pipeline, C classified as drugs, biologicals or dietary supplements, and D classified as new chemical or biological entities or repurposed drugs

Fig. 2

Flowchart of assessment of candidates against the eligibility criteria

Fig. 3

Visual representation of target product profile matching for candidates to prevent spontaneous preterm birth. A traffic light system to visualise each candidate for preterm birth prevention at A Phase III, B Phase II and C Phase I clinical development. Candidates are classified as met preferred (dark green), met minimum (light green), partially met minimum (yellow) and did not meet the minimum (red) requirements in the target product profiles. When insufficient information is available for a specific variable, they have been classified as not yet known (grey). *Target country is classified as trials being conducted in HIC and LMIC (dark green), HIC only or LMIC only (both yellow) or country not stated (grey). **Stability has been classified as does not require cold chain (green), requires cold chain (red) or unsure (grey). #WHO EML is classified as candidate is already on the WHO EML list (green), or candidate is not on the WHO EML list (red). Final rank has been determined by quantification of the matching to the target product profiles (see Tables S1 and S2 for details of quantification coding), with efficacy and safety given a greater weight than other variables. HIC = high-income country, LMIC = low- or middle-income country, EML = essential medicines list

Fig. 4

Visual representation of target product profile matching for candidates to manage preterm labor. A traffic light system to visualise each candidate for preterm labor treatment at A Phase III, B Phase II and C Phase I clinical development. Candidates are classified as met preferred (dark green), met minimum (light green), partially met minimum (yellow) and did not meet the minimum (red) requirements in the target product profiles. When insufficient information is available for a specific variable, they have been classified as not yet known (grey). *Target country is classified as trials being conducted in HIC and LMIC (dark green), HIC only or LMIC only (both yellow) or country not stated (grey). **Stability has been classified as does not require cold chain (green), requires cold chain (red) or unsure (grey). #WHO EML is classified as candidate is already on the WHO EML list (green), or candidate is not on the WHO EML list (red). Final rank has been determined by quantification of the matching to the target product profiles (see Tables S1 and S2 for details of quantification coding), with efficacy and safety given a greater weight than other variables. HIC = high-income country, LMIC = low- or middle-income country, EML = essential medicines list

Fig. 5

Details of the preclinical candidates in the R&D pipeline for preterm birth/labor. Summary of the preclinical candidates in the R&D pipeline for the prevention of preterm birth and treatment of preterm labor from 2000 – 2021. The proportion of candidates A in active development, and inactive (no publications since 2018), B classified as drugs, biologicals or dietary supplements, and C classified as new chemical or biological entities or repurposed drugs