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

BMC Pregnancy and Childbirth volume 23, Article number: 525 (2023) Cite this article

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.

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Background

Preterm birth (born alive prior to 37 completed weeks’ gestation) is the leading cause of death in children under five and a major cause of newborn morbidity [1,2,3]. Up to 50% of preterm births are due to spontaneous preterm labour [4]. There are limited medicines in clinical use for spontaneous preterm birth/labour. Several drugs can delay preterm labour—a 2022 Cochrane network meta-analysis on tocolytics found all subclasses (betamimetics, COX inhibitors, calcium channel blockers, magnesium sulfate, oxytocin receptor antagonists, nitric oxide donors) are probably effective at delaying preterm birth by 48 h, and that calcium channel blockers possibly reduce the risk of some adverse neonatal outcomes including respiratory and neurodevelopmental morbidity [5]. The World Health Organization (WHO) subsequently recommended the calcium channel blocker nifedipine as the preferred tocolytic agent, however noted a lack of long-term follow up studies [6]. All tocolytic drugs in clinical use, apart from atosiban, are repurposed medicines that are used off-label in pregnant women [7]. Fewer options are available for preventing spontaneous preterm birth – while vaginal progesterone can prevent preterm birth in high- risk women (women a history of spontaneous preterm birth or shortened cervix), some clinical indications for use (short cervical length, detected via ultrasound) are not easy to identify in all settings [8]. In October 2022, the FDA recommended Makena (injectable 17-alpha-hydroxyprogesterone caproate) be withdrawn from market due to evidence of a lack of clinical benefit in preventing preterm birth [9, 10].

The lack of innovation in medicines for spontaneous preterm birth/labour can be attributed to the broader, long-standing lack of investment in research and development (R&D) for new medicines for obstetric conditions [11]. A 2014 analysis of maternal research funding demonstrated that very few funders, particularly in the pharmaceutical industry, place a high priority on maternal health medicines R&D [12]. In 2008 there were fewer drugs in active development for all maternal conditions than for the rare disease amyotrophic lateral sclerosis [13]. This “drug drought” in maternal medicines has meant only two new drugs—the tocolytic atosiban and carbetocin for prevention of postpartum haemorrhage – have been licenced over the past 30 years specifically for use among pregnant women [14].

The Accelerating Innovation for Mothers (AIM) project was initiated to catalyse the development of new medicines for obstetric conditions [15]. Within AIM, we previously developed two target product profiles (TPPs) for new medicines to prevent spontaneous preterm birth and manage preterm labour [16]. TPPs are strategic documents that describe the key characteristics of new products and have helped drive R&D in vaccines, diagnostics and therapeutics for multiple conditions [17,18,19,20,21]. In this study, we aimed to analyse a database established by the AIM project [22,23,24] of the pipeline of medicines for preterm birth and compared candidates to the TPPs to identify the most promising options for reducing preterm birth-related morbidity and mortality globally.

Materials and methods

AIM database of drug development pipeline

Development of the AIM medicine pipeline database has been previously described [22,23,24,25]. Briefly, the database was created by systematically searching leading pharmaceutical databases (Adis Insight and Pharmaprojects), WHO international clinical trials registry platform (ICTRP) and other clinical trial registries, PubMed and grant databases of top maternal health product funders to identify candidate medicines (including drugs, dietary supplements and biologics) investigated for five priority maternal conditions (preeclampsia, preterm birth/labour, post-partum hemorrhage, fetal growth restriction and fetal distress). The AIM project database identified a total of 444 candidates that were investigated during the period 2000 to 2021. Candidates under investigation for preterm birth/labour were included in the database regardless of aetiology of preterm birth. Preterm labor/birth had the largest number of candidates for any of the five pregnancy-related conditions, with 178 unique candidates.

To identify high-potential candidates in the pipeline, we applied a systematic, stepwise approach to assessing all 178 candidates for preterm birth prevention and preterm labour management. First, we excluded candidates that were: 1) approved and already available on the market for this indication; 2) recommended by WHO, or otherwise in routine clinical use for this indication; 3) already recommended or widely used to treat a subgroup of women within the condition of interest (for example, levothyroxine in pregnant women with hypothyroidism); 4) inactive due to negative trial outcomes (such as adverse maternal or neonatal outcomes); 5) indicated as inferior to current treatments based on currently available evidence; and 6) under investigation for other conditions related to labour/birth, such as labour induction, and not preterm birth.

TPP matching of candidates in development phase I, II or III

We previously developed TPPs to guide development of novel medicines for prevention of spontaneous preterm birth and management of preterm labour – the first TPPs developed for preterm birth [26]. These TPPs included 21 parameters with “minimum” and “preferred” criteria defined for each parameter (Tables S1 and S2)—an ideal medicine would be one that met the preferred criteria for all 21 parameters. For the current analysis, we used a drug agnostic systematic matching approach [23], which utilises nine critical parameters from the TPPs as criteria to rank candidates in Phases I, II or III (Table 1, Table S1). These nine variables were selected based on their relative importance for wide-scale implementation, and the selection was informed by expert interviews during TPP development. TPP matching was performed for each candidate by two authors independently, and where differences arose, a third author was consulted to determine final matching.

Table 1 Critical parameters from target product profiles used to rank candidates in clinical development
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Preclinical candidates were assessed descriptively, including categorisation by product type, new or repurposed, and medicine subclass. Comparison of preclinical candidates to the TPPs was not performed, given the lack of data for most of the TPP-based criteria.

Data visualisation and ranking of potential

For each variable, candidates were assigned a numerical score representing the level of matching for a given variable of the TPP (Table 1 and Tables S1 and S2), as described in our previous study [23]. Given the greater importance of clinical efficacy and safety criteria, these variables were given a greater weight. These scores were also represented graphically – candidates were classified as having met preferred (dark green), met minimum (light green), partially met minimum (yellow) or did not meet minimum (red). Hence, the ranking of a candidate as high, medium or low is based on a systematic assessment of available evidence against pre-specified criteria.

Results

Of the 178 candidates in the pipeline, seven (3.9%) were approved and on the market for the prevention or management of preterm birth (allylestrenol, atosiban, injectable 17-alpha-hydroxyprogesterone caproate, hexoprenaline, isoxsuprine, fenoterol, ritodrine). An additional 11/178 (6.2%) candidates are approved for other clinical conditions and have been used off-label for preterm birth (terbutaline, salbutamol, vaginal/topical progesterone, magnesium sulphate, orciprenaline, nicardipine, nifedipine, indomethacin, sulindac) or to promote fetal well-being following preterm delivery (dexamethasone, betamethasone).

In total, 68 (38.2%) candidates were currently active and 110 (61.8%) were inactive (no updates since 2018; Fig. 1A). The majority (107 candidates; 60.1%) were at the preclinical stage of development (Fig. 1B). In total, 11 candidates were in Phase I (6.2%), 30 candidates in Phase II (16.9%), 23 candidates in Phase III (12.9%) and 7 candidates in Phase IV (3.9%). Across all 178 candidates, 132 (74.1%) were classified as drugs, 14 (7.9%) were biologics and 32 (18.0%) were dietary supplements (Fig. 1C). In total, 82 (46.1%) were new chemical/biological entities and 96 (53.9%) were repurposed (Fig. 1D). Of the 71 candidates in clinical development, 27 were removed from further analysis due to the exclusion criteria, leaving 44 candidates (Fig. 2). In total, 10 clinical phase candidates were ranked as high potential, 7 as medium potential and 27 as low potential.

Fig. 1
figure 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

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Fig. 2
figure 2

Flowchart of assessment of candidates against the eligibility criteria

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Prevention of spontaneous preterm birth

Eight candidates were assessed for prevention in Phase III clinical trials (Fig. 3a), 10 in Phase II (Fig. 3b) and three in Phase I (Fig. 3c). Six candidates were ranked as high potential and two as medium potential. The evidence for candidates ranked low potential is presented in Additional file 2: Appendix B.

Fig. 3
figure 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

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Phase III candidates

Aspirin, vaginal/topical progesterone and omega-3 fatty acids supplementation were ranked as high potential (Fig. 3a). A 2021 individual participant data meta-analysis found that vaginal progesterone reduces the risk of preterm birth (nine trials, 3769 women, RR 0.78, 95% CI 0.68 – 0.90) in women at increased risk, defined as women with a history of preterm birth and/or short cervix (< 25 mm) [8]. A 2018 Cochrane review examining omega-3 fatty acid supplementation during pregnancy found high quality evidence of a reduced risk of preterm birth < 37 weeks (26 trials, 10,304 women, RR 0.89, 95% CI 0.81 – 0.97) and < 34 weeks (9 trials, 5204 women, RR 0.58, 95% CI 0.44 – 0.77) [27]. Meta-analysis of 35 placebo-controlled trials found taking low dose aspirin during pregnancy reduced the risk of preterm birth (46,568 women, RR 0.90, 95% CI 0.86 – 0.94) [28], however, it is unclear if aspirin is beneficial in preventing spontaneous preterm birth, or if this benefit relates to the known effects of aspirin in reducing the risk of preeclampsia [29]. A 2017 individual participant data meta-analysis including 17 trials (including 28,797 women) evaluating aspirin for the prevention of preeclampsia, found that aspirin reduced the risk of spontaneous preterm birth at < 37 weeks (RR 0.93, 95% CI 0.86 – 0.996) and < 34 weeks (RR 0.86, 95% CI 0.76 – 0.99) [30]. Similar reductions were observed in a 2018 secondary analysis of a trial investigating the effect of low-dose aspirin to prevent preeclampsia. In women with a low risk of preeclampsia, aspirin reduced the odds of spontaneous preterm birth < 34 weeks’ gestation compared to placebo (OR 0.43, 95% CI 0.26 – 0.84; 2543 women) [31]. However, the 2022 APRIL trial assessed the effects of aspirin prophylaxis in 406 women with a history of preterm birth, and found no significant difference in the risk of preterm birth (RR 0.83, 95% CI 0.58 – 1.20) [32].

Pravastatin was ranked as medium potential (Fig. 3a). The clinical efficacy of pravastatin for preventing spontaneous preterm birth remains unknown. A 2021 meta-analysis of trials and observational studies found that any statin use during pregnancy was associated with a non-significant reduction in the risk of preterm birth (four studies, 483 women, OR 0.47, 95% CI 0.06 – 3.70), but also a significant increase in risk of spontaneous abortion (six studies, 4,165 women, OR 1.36, 95% CI 1.10 – 1.68) [33]. One mechanism by which pravastatin is thought to prevent preterm birth is by preventing preeclampsia [34], however a 2021 Phase III trial in 1120 women reported that pravastatin was not effective for this indication [35].

Phase II candidates

Oral progesterone, the amino-acid L-arginine and the trace element selenium were ranked high potential (Fig. 3b). A 2021 individual participant data meta-analysis of progesterone for preventing preterm birth found oral progesterone reduced the risk of preterm birth < 24 weeks (RR 0.60, 95% CI 0.41 – 0.90) [8]. However, this only included 2 trials of 183 women and more evidence is required to evaluate clinical efficacy. Meta-analysis of L-arginine supplementation in women at high risk of preeclampsia or with mild chronic hypertension showed it reduces the risk of preterm birth (three trials, 625 women, RR 0.50, 95% CI 0.30 – 0.85) [36]. While there are currently no clinical trials examining the effects of L-arginine supplementation on prevention of spontaneous preterm birth, a prospective cohort study of 7591 pregnant women in Tanzania found that the level of L-arginine dietary intake was associated with a decreased risk of spontaneous preterm birth [37].

Evidence of clinical efficacy of selenium is limited to a small trial in 180 HIV-positive pregnant women that found selenium reduced the risk of preterm birth (RR 0.32, 95% CI 0.11 – 0.96) [38]. Meta-analysis of observational data has also reported an association between prenatal maternal selenium plasma concentrations and reduced odds of preterm birth (17 cohorts, 9946 singleton births, OR 0.95, 95% CI 0.90 – 1.0) [39].

Phase I candidates

Lactoferrin was ranked as medium potential (Fig. 3c), and there is evidence from a small trial of 125 pregnant women with bacterial vaginosis that vaginal lactoferrin significantly reduced the rate of preterm birth (25.0% vs 44.6%, p = 0.02) [40]. However, lactoferrin did not meet the minimum requirements for companion diagnostics, as it requires a diagnosis of bacterial vaginosis, which involves laboratory testing of vaginal discharge to identify the causative agent. Additional laboratory diagnostic testing may act as a barrier to implementation in some settings.

Management of preterm labour

There were four candidates assessed for management of preterm labour in Phase III (Fig. 4a), 13 in Phase II (Fig. 4b) and five in Phase I (Fig. 4c). Four candidates were ranked as high potential and five as medium potential. The evidence for candidates ranked low potential is presented in Additional file 2: Appendix B.

Fig. 4
figure 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

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Phase III candidates

No Phase III candidates were identified as high potential. Retosiban, a selective oxytocin antagonist and glyceryl trinitrate, a nitric oxide donor were ranked medium potential (Fig. 4a). A pilot trial of 29 pregnant women suggested retosiban has a favourable safety and tolerability profile [41]. A small placebo-controlled trial of 64 women in preterm labour found retosiban significantly prolonged pregnancy by an average of 8.2 days and reduced the risk of preterm birth (RR 0.38, 95% CI 0.15 – 0.81) [42]. A Phase III trial of retosiban compared to placebo or atosiban was stopped early due to failure to recruit [43]. Data from this stopped trial suggested a possible increase in time to delivery compared to placebo (23 women) and no significant difference in time to delivery between retosiban and atosiban (97 women). The 2022 Cochrane network meta-analysis on tocolytics found that nitric oxide donors such as Glyceryl trinitrate (13 trials) probably delay preterm birth by 48 h (RR 1.17, 95% CI 1.05 – 1.31) and 7 days (RR 1.18, 95% CI 1.02 – 1.37) [5].

Phase II candidates

Nicardipine, nicorandil, isosorbide dinitrate and celecoxib were all ranked high potential and are all from the same drug class as tocolytics in clinical use (Fig. 4b). Nicardipine and nicorandil are calcium channel blockers, isosorbide dinitrate is a nitric oxide donor and celecoxib is a COX-2 inhibitor. The 2022 Cochrane network meta-analysis found that calcium channel blockers, nitric oxide donors and COX-2 inhibitors were all effective in delaying preterm birth compared to placebo or no tocolytic [5]. COX inhibitors and calcium channel blockers are both possibly effective at delaying birth by 48 h (RR 1.11, 95% CI 1.01 – 1.23, and RR 1.16, 95% CI 1.07 – 1.24, respectively). Calcium channel blockers are also probably effective at delaying preterm birth by 7 days (RR 1.15, 95% CI 1.04 – 1.27), however are probably more likely to result in cessation of treatment (RR 1.23, 95% CI 1.23 – 7.11). Importantly, calcium channel blockers possibly reduce the risk of adverse neonatal outcomes including neurodevelopmental morbidity (RR 0.51, 95% CI 0.30 – 0.85), respiratory morbidity (RR 0.68, 95% CI 0.53 – 0.88) and low birthweight (RR 0.49, 95% CI 0.28 – 0.87) [5]. As mentioned above, nitric oxide donors (13 trials) probably delay preterm birth and are ranked highest for delaying birth by 48 h and 7 days [5].

Human chorionic gonadotropin and relcovaptan were ranked medium potential (Fig. 4b). A placebo-controlled trial of 100 pregnant women suggested human chorionic gonadotropin can significantly delay labour [44] while two other trials (165 pregnant women) suggest it is as effective as magnesium sulfate at delaying labour for 48 h, with fewer side-effects [45, 46]. A pilot trial (18 women) of relcovaptan, an orally active vasopressin V1a receptor inhibitor, found it effectively reduced uterine contractions during premature labour compared to placebo [47], however development was discontinued in 2001 before the results of Phase II trials in Sweden, France and Poland were reported.

Phase I candidates

Bryophyllum pinnatum extract, a herbal succulent that contained phenolic constituents was ranked medium potential (Fig. 4c). The authors of a trial of 26 pregnant women comparing Bryophyllum pinnatum extract to nifedipine suggested it might be promising, but the study was stopped early due to poor recruitment [48].

Preclinical candidates

Of the 107 candidates in preclinical development, 15 were excluded due to adverse effects, being inferior to other products in development or being used preclinically as a research tool to investigate pathophysiology and not intended for clinical translation. Of the 92 remaining candidates, 28 (30.4%) were active and 64 (69.6%) were inactive (Fig. 5A). Most candidates were drugs (70 candidates, 76.1%); 13 were dietary supplements (14.1%) and 9 were biologics (9.8%; Fig. 5B). There were 36 repurposed medicines (39.1%) and 56 new chemical or biological entities (60.9%; Fig. 5C). Overall, 34 candidates were evaluated for the prevention of preterm birth, 56 were evaluated for the management of preterm labour and two were evaluated for both the prevention and management (resveratrol and rolipram).

Fig. 5
figure 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

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A diverse range of medicine subclasses were under investigation at the preclinical stage (Tables 2 and 3). The most common preclinical medicine subclass for prevention were amino acid/peptides (14 candidates, 38.9%; Table 2). Amino acid/peptides were also the most common subclass for management of preterm labour (12 candidates, 20.7%) followed by tocolytics and vascular agents (10 candidates each, 17.2%; Table 3). We identified 13 candidates with some concerns and six candidates with major concerns about the quality of the preclinical evidence. Concerns identified included lack of preterm birth animal model studies, conflicting results between studies of the same candidate and extremely high dose of candidate medicine used in preclinical studies.

Table 2 Summary of preclinical candidates for preterm birth prevention
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Table 3 Summary of preclinical candidates for preterm labour management
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Discussion

Main findings

We systematically analysed the medicines R&D pipeline for preterm birth/labor between 2000 and 2021. Of the 178 candidates approximately 4% have made it to market for this indication. Novel medicines accounted for 46% of candidates in clinical development for management of preterm labour, a substantially higher proportion compared to other maternal conditions [25]. However, we identified only one novel medicine – oral 17-alpha-hydroxyprogesterone caproate—in clinical development for preterm birth prevention. Through matching candidates to pre-specified TPP criteria, we identified six high priority candidates for spontaneous preterm birth prevention (omega-3 fatty acids, aspirin, vaginal and oral progesterone, pravastatin, l-arginine and selenium) and four high priority candidates for management of preterm labour (nicorandil, isosorbide dinitrate, nicardipine and celecoxib), which warrant R&D investment.

Interpretation in light of other evidence

A 2008 analysis of the obstetric R&D pipeline identified 67 candidates in development for maternal conditions between 1980 and 2007 [13]; in contrast, we identified 444 candidates in development for five obstetric conditions between 2000 and 2021. Both studies found preterm birth/labor to be the dominant indication (45% and 40%, respectively), contributing the greatest number of individual candidates in the pipeline [13]. Given that preterm birth is the leading cause of mortality in newborns and children globally, this is perhaps unsurprising [49]. In high-income countries, where the majority of global research funding is spent [50], preterm birth is a leading cause of long-term disability and imposes significant societal and financial costs [51].

Most candidates in the preterm birth pipeline that had made it to market or were used extensively off-label were tocolytics. Our analysis identified four high- and five medium-potential candidate tocolytics, in addition to the tocolytics currently available. Strikingly, all high potential and two medium potential candidates are from the same drug classes as known effective tocolytics, including COX-inhibitors (celecoxib), nitric oxide donors (isosorbide dinitrate, glyceryl trinitate), oxytocin receptor antagonists (retosiban) and calcium channel blockers (nicorandil, nicardipine) [6]. Our analysis highlights the relatively strong interest in R&D for improved tocolytics, likely because of the efficacy evidence on drugs within the same class and that the mechanisms underlying labour progression are well characterised, providing specific drug targets [52].

In contrast, there are currently few medicines that are recommended for the prevention of preterm birth. A significant amount of active R&D concerns progestin medicines for preterm birth prevention. Studies have investigated different formulations and routes of administration (such as vaginal and oral natural micronized progesterone), as well as aiming to identify which sub-population of women will benefit most from progesterone [8]. Recently, evidence was in favour of using vaginally administered progesterone in women at increased risk of preterm birth, particularly women with a short cervix [8], and hence some guidelines recommended its use for preventing preterm birth in women with a history of preterm birth and/or cervical shortening [53,54,55]. However, a 2022 meta-analysis found that progesterone was not effective in preventing recurrent preterm birth in women with a history of spontaneous preterm birth, in the absence of cervical shortening [56]. Assessment of cervical length requires access to transvaginal ultrasound, which is not available in all settings. Two meta-analyses from 2021 found no significant effect of injectable 17-alpha-hydroxyprogesterone caproate in preventing preterm birth, prompting the FDA, in 2022, to recommend its withdrawal from market [8, 57]. These recent additions to the body of evidence on progesterone’s efficacy have prompted updated guidance from American College of Obstetricians and Gynecologists (ACOG) on use of progesterone in pregnant women [58]. Pending the FDA final determination, hydroxyprogesterone caproate injection continues to be recommended by the International Federation of Obstetrics and Gynaecology (FIGO) in women at risk of spontaneous preterm birth [53].

Dietary supplements represented 18% of the candidates under investigation for preterm birth. Trials of some of these supplements, including vitamins A, C and E, have been conclusively shown not to be effective at preventing preterm birth [59,60,61]. In contrast, omega-3 fatty acids, L-arginine and selenium supplementation all have promising clinical efficacy evidence, though further evidence is needed [27, 36, 38]. There are clear implementation advantages for dietary supplements – they are usual taken orally, many are low cost and widely available, and they may be viewed as natural supplements rather than drugs, which could be more acceptable to women [62]. However, questions remain about the population of women who would benefit most from these supplements, and whether companion diagnostic tests for vitamin and mineral deficiencies are required [63] which can be a barrier to implementation.

The large number of candidates in development for preterm birth/labor suggests comparatively high R&D interest for this condition. However, 62% of all candidates and 72% of candidates in preclinical development for preterm birth/labor are inactive, with no updates or published progress since 2018. For example, the promising oxytocin receptor antagonist retosiban developed by GSK was halted in Phase III trials due to difficulties with trial recruitment [43]. The complexities of conducting large, well-designed clinical trials in pregnant women is a recognised barrier inhibiting R&D for maternal conditions [15]. A 2013 review of all US-based, phase IV, pharmaceutical industry-sponsored clinical trials that included women of childbearing age between 2011–2012, found that only 1% were specifically designed for pregnant women, and 95% specifically excluded pregnant women [64]. Pharmaceutical industry representatives cite potential liability issues, additional risks related to teratogenicity and the prohibitively large sample sizes needed to demonstrate benefit as the reasons for the lack of R&D in maternal medicines [15]. To overcome these barriers, broader international coordinated efforts around high potential candidates is needed. Successful strategies have been implemented to overcome similar barriers in the development of medicines for children. For example, in 2007, “Paediatric Investigation Plans” (PIP) were introduced by the European Union, obliging companies applying for licences for new medicines to present a plan to study the medicine in children (unless inappropriate for this age group). This scheme greatly improved the product pipeline for children’s medicines, leading to over 260 new medicines or indications for children since its launch [65]. There remains an urgent need for large trials for candidate medicines for the prevention of preterm birth and the management of spontaneous preterm labor, which are adequately powered for clinically relevant neonatal outcomes.

Strengths and limitations

We have developed a novel, drug-agnostic approach for analysing the R&D pipeline for medicines for spontaneous preterm birth and preterm labor. Our analysis provides the most extensive mapping of the historic and current R&D pipeline for preterm birth/labor and identified ten high priority candidates currently in clinical development, as well as significant gaps in R&D. This approach may be useful for prioritising research for other maternal conditions, as well as other fields of drug development, particularly where TPPs already exist [18]. However, there are some limitations to this approach. Firstly, ranking of candidates relied on available information, and it is possible that data on some candidates are not publicly available. Secondly, this system of matching candidates to the TPPs was not possible for candidates in preclinical development, due to a lack of available data on many variables in the TPPs. Thus, when examining preclinical candidates, other factors such as the quality of the laboratory findings should be considered prior to further investments in clinical trials. Finally, preterm birth is a broad category that can involve many different aetiologies. It is highly unlikely that a single drug could be effective in all forms of preterm birth. All medicines under investigation for preterm birth were included in the database, as the specific aetiology an individual medicine was targeting was often poorly articulated. In the current study we analysed each candidate medicine against the TPPs for medicines to prevent spontaneous preterm birth, as this was highlighted during TPP development as the specific target population most in need [16]. As advances are made in the understanding of the causes of preterm birth the TPP, a living document, and the pipeline analysis can be updated to address additional pathologies.

Conclusion

Over the last 20 years R&D for preterm birth/labor medicines is an active area compared to other maternal conditions. However, many candidates, including promising new therapies, are currently inactive. Development of alternative tocolytics, new formulations of progestins and dietary supplements are areas of high research activity. We identified six high priority candidates for preventing spontaneous preterm birth and four high priority candidates for the management of preterm labor that best meet real-world requirements. This novel method of matching drug candidates to TPPs can help better direct research funding towards the most promising candidates and ensure new and effective therapies become available.

Availability of data and materials

All data relevant to the study are included in the article or uploaded as supplementary information. The database generated and analysed during the current study are available at https://www.conceptfoundation.org/accelerating-innovation-for-mothers/.

Abbreviations

ACOG:

American College of Obstetricians and Gynecologists

AIM:

Accelerating Innovation for Mothers

COX:

Cyclooxygenase

FDA:

Food and Drug Administration

FIGO:

Fédération Internationale de Gynécologie et d'Obstétrique

GSK:

GlaxoSmithKline plc.

R&D:

Research and development

TPP:

Target product profile

WHO:

World Health Organization

References

  1. Hug L, Alexander M, You D, Alkema L, Estimation UNI-aGfCM. National, regional, and global levels and trends in neonatal mortality between 1990 and 2017, with scenario-based projections to 2030: a systematic analysis. Lancet Glob Health. 2019;7(6):e710–20.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Cheong JL, Doyle LW, Burnett AC, Lee KJ, Walsh JM, Potter CR, et al. Association between moderate and late preterm birth and neurodevelopment and social-emotional development at age 2 years. JAMA Pediatr. 2017;171(4):e164805.

    Article  PubMed  Google Scholar 

  3. Stoll BJ, Hansen NI, Bell EF, Walsh MC, Carlo WA, Shankaran S, et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993–2012. JAMA. 2015;314(10):1039–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Morisaki N, Togoobaatar G, Vogel JP, Souza JP, Rowland Hogue CJ, Jayaratne K, et al. Risk factors for spontaneous and provider-initiated preterm delivery in high and low Human Development Index countries: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health. BJOG. 2014;121(Suppl 1):101–9.

    Article  PubMed  Google Scholar 

  5. Wilson A, Hodgetts-Morton VA, Marson EJ, Markland AD, Larkai E, Papadopoulou A, et al. Tocolytics for delaying preterm birth: a network meta-analysis (0924). Cochrane Database Syst Rev. 2022;8:CD014978.

    PubMed  Google Scholar 

  6. WHO recommendation on tocolytic therapy for improving preterm birth outcomes. Geneva: World Health Organization; 2022. Licence: CC BY-NC-SA 3.0 IGO.

  7. Husslein P. Development and clinical experience with the new evidence-based tocolytic atosiban. Acta Obstet Gynecol Scand. 2002;81(7):633–41.

    Article  PubMed  Google Scholar 

  8. Group E. Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials. Lancet. 2021;397(10280):1183–94.

    Article  Google Scholar 

  9. Chang CY, Nguyen CP, Wesley B, Guo J, Johnson LL, Joffe HV. Withdrawing approval of Makena - a proposal from the FDA center for drug evaluation and research. N Engl J Med. 2020;383(24):e131.

    Article  PubMed  Google Scholar 

  10. Federal register: proposal to withdraw approval of MAKENA; hearing - a notice by the food and drug administration on 08/17/2022. Available from: https://www.federalregister.gov/documents/2022/08/17/2022-17715/proposal-to-withdraw-approval-of-makena-hearing.

  11. The Lancet Global H. Progressing the investment case in maternal and child health. Lancet Glob Health. 2021;9(5):e558.

    Article  Google Scholar 

  12. Footman K, Chersich M, Blaauw D, Campbell OM, Dhana A, Kavanagh J, et al. A systematic mapping of funders of maternal health intervention research 2000–2012. Global Health. 2014;10:72.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Fisk NM, Atun R. Market failure and the poverty of new drugs in maternal health. PLoS Med. 2008;5(1):e22.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Bhattacharya S, Innovation BHPCfRS. Safe and effective medicines for use in pregnancy: a call to action. Birmingham: University of Birmingham; 2021.

    Google Scholar 

  15. Foundation C. Medicines for pregnancy specific conditions: research, development and market analysis. 2021. Available from: https://www.conceptfoundation.org/global-news/medicines-for-pregnancy-specific-conditions-research-development-and-market-analysis/.

    Google Scholar 

  16. McDougall ARA, Tuttle A, Goldstein M, Ammerdorffer A, Aboud L, Gulmezoglu AM, et al. Expert consensus on novel medicines to prevent preterm birth and manage preterm labour: target product profiles. BJOG. 2022. Online ahead of print.

  17. World Health Organization. WHO target product profiles, preferred product characteristics, and target regimen profiles: standard procedure V1.02. Geneva: World Health Organization; 2020.

  18. Lewin SR, Attoye T, Bansbach C, Doehle B, Dube K, Dybul M, et al. Multi-stakeholder consensus on a target product profile for an HIV cure. Lancet HIV. 2021;8(1):e42–50.

    Article  CAS  PubMed  Google Scholar 

  19. Murtagh M, Blondeel K, Peeling RW, Kiarie J, Toskin I. The relevance of target product profiles for manufacturers, experiences from the World Health Organization initiative for point-of-care testing for sexually transmitted infections. Arch Public Health. 2021;79(1):187.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Pelle KG, Rambaud-Althaus C, D’Acremont V, Moran G, Sampath R, Katz Z, et al. Electronic clinical decision support algorithms incorporating point-of-care diagnostic tests in low-resource settings: a target product profile. BMJ Glob Health. 2020;5(2):e002067.

    Article  PubMed  PubMed Central  Google Scholar 

  21. WHO. Target product profiles for needed antibacterial agents: enteric fever, gonorrhoea, neonatal sepsis, urinary tract infections and meeting report. Geneva: World Health Organisation; 2020. Contract No.: Licence: CC BY-NC-SA 3.0 IGO.

    Google Scholar 

  22. Lim S, McDougall ARA, Goldstein M, Tuttle A, Hastie R, Tong S, et al. Analysis of a maternal health medicines pipeline database 2000–2021: new candidates for the prevention and treatment of fetal growth restriction. BJOG. 2023;130(6):653–63.

  23. McDougall ARA, Hastie R, Goldstein M, Tuttle A, Tong S, Ammerdorffer A, et al. Systematic evaluation of the pre-eclampsia drugs, dietary supplements and biologicals pipeline using target product profiles. BMC Med. 2022;20(1):393.

    Article  PubMed  PubMed Central  Google Scholar 

  24. McDougall AR, Goldstein M, Tuttle A, Ammerdorffer A, Rushwan S, Hastie R, et al. Innovations in the prevention and treatment of postpartum hemorrhage: analysis of a novel medicines development pipeline database. Int J Gynecol Obstet. 2022;158(Suppl 1):31–9.

    Article  Google Scholar 

  25. Foundation C. Accelerating innovation for mothers: pipeline candidates Geneva, Switzerland. Concept Foundation; 2021. Available from: https://www.conceptfoundation.org/accelerating-innovation-for-mothers/aim-pipeline-candidates/.

  26. Foundation C. Accelerating innovation for mothers: target product profiles Geneva, Switzerland. Concept Foundation; 2021. Available from: https://www.conceptfoundation.org/accelerating-innovation-for-mothers/target-product-profiles/.

  27. Middleton P, Gomersall JC, Gould JF, Shepherd E, Olsen SF, Makrides M. Omega-3 fatty acid addition during pregnancy. Cochrane Database Syst Rev. 2018;11:CD003402.

    PubMed  Google Scholar 

  28. Choi YJ, Shin S. Aspirin prophylaxis during pregnancy: a systematic review and meta-analysis. Am J Prev Med. 2021;61(1):e31–45.

    Article  PubMed  Google Scholar 

  29. WHO recommendations on antiplatelet agents for prevention of pre-eclampsia. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO.

  30. van Vliet EOG, Askie LA, Mol BWJ, Oudijk MA. Antiplatelet agents and the prevention of spontaneous preterm birth: a systematic review and meta-analysis. Obstet Gynecol. 2017;129(2):327–36.

    Article  PubMed  Google Scholar 

  31. Andrikopoulou M, Purisch SE, Handal-Orefice R, Gyamfi-Bannerman C. Low-dose aspirin is associated with reduced spontaneous preterm birth in nulliparous women. Am J Obstet Gynecol. 2018;219(4):399 e1-e6.

    Article  PubMed  Google Scholar 

  32. Landman A, de Boer MA, Visser L, Nijman TAJ, Hemels MAC, Naaktgeboren CN, et al. Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study): a multicentre, randomised, double-blinded, placebo-controlled trial. PLoS Med. 2022;19(2):e1003892.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Vahedian-Azimi A, Bianconi V, Makvandi S, Banach M, Mohammadi SM, Pirro M, et al. A systematic review and meta-analysis on the effects of statins on pregnancy outcomes. Atherosclerosis. 2021;336:1–11.

    Article  CAS  PubMed  Google Scholar 

  34. de Alwis N, Beard S, Mangwiro YT, Binder NK, Kaitu’u-Lino TJ, Brownfoot FC, et al. Pravastatin as the statin of choice for reducing pre-eclampsia-associated endothelial dysfunction. Pregnancy Hypertens. 2020;20:83–91.

    Article  PubMed  Google Scholar 

  35. Dobert M, Varouxaki AN, Mu AC, Syngelaki A, Ciobanu A, Akolekar R, et al. Pravastatin versus placebo in pregnancies at high risk of term preeclampsia. Circulation. 2021;144(9):670–79.

  36. Goto E. Effects of prenatal oral L-arginine on birth outcomes: a meta-analysis. Sci Rep. 2021;11(1):22748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Darling AM, McDonald CR, Urassa WS, Kain KC, Mwiru RS, Fawzi WW. Maternal dietary L-arginine and adverse birth outcomes in Dar es Salaam, Tanzania. Am J Epidemiol. 2017;186(5):603–11.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Okunade KS, Olowoselu OF, John-Olabode S, Hassan BO, Akinsola OJ, Nwogu CM, et al. Effects of selenium supplementation on pregnancy outcomes and disease progression in HIV-infected pregnant women in Lagos: a randomized controlled trial. Int J Gynaecol Obstet. 2021;153(3):533–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Monangi N, Xu H, Khanam R, Khan W, Deb S, Pervin J, et al. Association of maternal prenatal selenium concentration and preterm birth: a multicountry meta-analysis. BMJ Glob Health. 2021;6(9):e005856.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Miranda M, Saccone G, Ammendola A, Salzano E, Iannicelli M, De Rosa R, et al. Vaginal lactoferrin in prevention of preterm birth in women with bacterial vaginosis. J Matern Fetal Neonatal Med. 2021;34(22):3704–8.

    Article  CAS  PubMed  Google Scholar 

  41. Thornton S, Valenzuela G, Baidoo C, Fossler MJ, Montague TH, Clayton L, et al. Treatment of spontaneous preterm labour with retosiban: a phase II pilot dose-ranging study. Br J Clin Pharmacol. 2017;83(10):2283–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Thornton S, Miller H, Valenzuela G, Snidow J, Stier B, Fossler MJ, et al. Treatment of spontaneous preterm labour with retosiban: a phase 2 proof-of-concept study. Br J Clin Pharmacol. 2015;80(4):740–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Saade GR, Shennan A, Beach KJ, Hadar E, Parilla BV, Snidow J, et al. Randomized trials of retosiban versus placebo or atosiban in spontaneous preterm labor. Am J Perinatol. 2021;38(S 01):e309–17.

    Article  PubMed  Google Scholar 

  44. Ali AFM, Fateena B, Ezzeta A, Badawya H, Ramadana A, El-tobge A. Treatment of preterm labor with human chorionic gonadotropin: a new modality - Abstract. Am J Obstet Gynecol. 2000;95:S61.

    Google Scholar 

  45. Lorzadeh N, Dehnoori A, Moumennasab M. Human chorionic gonadotropin (hCG) versus magnesium sulfate to arrest preterm. Yafteh. 2004;5:41–6.

    Google Scholar 

  46. Sakhavar N, Mirteimoori M, Teimoori B. Magnesium sulfate versus hCG (Human Chorionic Gonadotropin) in suppression of preterm labor. Shiraz E-Med J. 2008;9:134–40.

    Google Scholar 

  47. Steinwall M, Bossmar T, Brouard R, Laudanski T, Olofsson P, Urban R, et al. The effect of relcovaptan (SR 49059), an orally active vasopressin V1a receptor antagonist, on uterine contractions in preterm labor. Gynecol Endocrinol. 2005;20(2):104–9.

    Article  CAS  PubMed  Google Scholar 

  48. Simoes-Wust AP, Lapaire O, Hosli I, Wachter R, Furer K, Schnelle M, et al. Two randomised clinical trials on the use of Bryophyllum pinnatum in preterm labour: results after early discontinuation. Complement Med Res. 2018;25(4):269–73.

    Article  PubMed  Google Scholar 

  49. Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, et al. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet. 2015;385(9966):430–40.

    Article  PubMed  Google Scholar 

  50. White C. Global spending on health research still skewed towards wealthy nations. BMJ. 2004;329(7474):1064.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Petrou S, Yiu HH, Kwon J. Economic consequences of preterm birth: a systematic review of the recent literature (2009–2017). Arch Dis Child. 2019;104(5):456–65.

    Article  PubMed  Google Scholar 

  52. Ilicic M, Zakar T, Paul JW. The Regulation of uterine function during parturition: an update and recent advances. Reprod Sci. 2020;27(1):3–28.

    Article  PubMed  Google Scholar 

  53. Shennan A, Suff N, Leigh Simpson J, Jacobsson B, Mol BW, Grobman WA, et al. FIGO good practice recommendations on progestogens for prevention of preterm delivery. Int J Gynaecol Obstet. 2021;155(1):16–8.

    Article  PubMed  PubMed Central  Google Scholar 

  54. RANZCOG. Progesterone: use in the second and third trimester of pregnancy for the prevention of preterm birth. Melbourne, Australia; Royal Australian and New Zealand College of Obstetricians and Gynaecologists. 2017.

  55. American College of O, Gynecologists’ Committee on Practice B-O. Prediction and prevention of spontaneous preterm birth: ACOG Practice Bulletin, Number 234. Obstet Gynecol. 2021;138(2):e65–90.

    Article  Google Scholar 

  56. Conde-Agudelo A, Romero R. Vaginal progesterone does not prevent recurrent preterm birth in women with a singleton gestation, a history of spontaneous preterm birth, and a midtrimester cervical length >25 mm. Am J Obstet Gynecol. 2022;227(6):923–6.

    Article  CAS  PubMed  Google Scholar 

  57. Almutairi AR, Aljohani HI, Al-Fadel NS. 17-alpha-hydroxyprogesterone vs. placebo for preventing of recurrent preterm birth: a systematic review and meta-analysis of randomized trials. Front Med. 2021;8:764855.

    Article  Google Scholar 

  58. Simhan HN, Bryant A, Gandhi M, Turrentine M, Gynecologists” ACoOa. Updated clinical guidance for the use of progesterone supplementation for the prevention of recurrent preterm birth. Washington: American College of Obstetricians and Gynecologists; 2023.

    Google Scholar 

  59. Rumbold A, Ota E, Nagata C, Shahrook S, Crowther CA. Vitamin C supplementation in pregnancy. Cochrane Database Syst Rev. 2015;9:CD004072.

    Google Scholar 

  60. Rumbold A, Ota E, Hori H, Miyazaki C, Crowther CA. Vitamin E supplementation in pregnancy. Cochrane Database Syst Rev. 2015;(9):CD004069.

  61. McCauley ME, van den Broek N, Dou L, Othman M. Vitamin A supplementation during pregnancy for maternal and newborn outcomes. Cochrane Database Syst Rev. 2015;(10):CD008666.

  62. Kennedy DA, Lupattelli A, Koren G, Nordeng H. Herbal medicine use in pregnancy: results of a multinational study. BMC Complement Altern Med. 2013;13:355.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Heaney RP. Vitamin D–baseline status and effective dose. N Engl J Med. 2012;367(1):77–8.

    Article  CAS  PubMed  Google Scholar 

  64. Shields KE, Lyerly AD. Exclusion of pregnant women from industry-sponsored clinical trials. Obstet Gynecol. 2013;122(5):1077–81.

    Article  PubMed  Google Scholar 

  65. Report from the Commission to the European Parliament and the Council. State of paediatric medicines in the EU: 10 years of the EU Paediatric regulation. COM (2017) 626. European Commission; 2017.

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Acknowledgements

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Funding

This research was funded by The Bill and Melinda Gates Foundation. The funders played no role in the design of the study, collection, analysis and inteptretation of the data, or in writing the manuscript.

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Authors and Affiliations

  1. Maternal, Child and Adolescent Health Program, Burnet Institute, 85 Commercial Road, Melbourne, VIC, 3004, Australia

    Annie R. A. McDougall & Joshua P. Vogel

  2. Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Australia

    Roxanne Hastie

  3. Policy Cures Research, Sydney, Australia

    Maya Goldstein & Andrew Tuttle

  4. Concept Foundation, Geneva, Switzerland

    Anne Ammerdorffer & A. Metin Gülmezoglu

  5. School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia

    Joshua P. Vogel

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  4. Andrew Tuttle
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Contributions

JPV and AMG led the conceptualisation and supervision of the project and funding acquisition. AMcD, RH, AT and MG were involved in conceptualisation of the project and development of the methodology. AA was involved in conceptualisation of the project, funding acquisition and project administration. AMcD and RH performed collection, management, visualisation and analysis of all data. All authors were involved in interpretation of data. AMcD wrote the original draft of the manuscript and all authors contributed to writing and editing and had full access to the data. AMcD and JPV has accessed and verified all the data in this study. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

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Correspondence to Annie R. A. McDougall.

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Supplementary Information

Additional file 1: Appendix A.

Supplementary tables. Table S1. Scoring of target product profile comparison, for quantification of potential of candidates. Table S2. Threshold for ranking of potential at each phase of the R&D development pipeline.

Additional file 2: Appendix B.

Low rank candidates.

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McDougall, A.R.A., Hastie, R., Goldstein, M. et al. New medicines for spontaneous preterm birth prevention and preterm labour management: landscape analysis of the medicine development pipeline. BMC Pregnancy Childbirth 23, 525 (2023). https://doi.org/10.1186/s12884-023-05842-9

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BMC Pregnancy and Childbirth

ISSN: 1471-2393

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