Systematic evaluation of the pre-eclampsia drugs, dietary supplements and biologicals pipeline using target product profiles

Annie R A McDougall; Roxanne Hastie; Maya Goldstein; Andrew Tuttle; Stephen Tong; Anne Ammerdorffer; A Metin Gülmezoglu; Joshua P Vogel

doi:10.1186/s12916-022-02582-z

Systematic evaluation of the pre-eclampsia drugs, dietary supplements and biologicals pipeline using target product profiles

BMC Med. 2022 Nov 4;20(1):393. doi: 10.1186/s12916-022-02582-z.

Authors

Annie R A McDougall¹, Roxanne Hastie², Maya Goldstein³, Andrew Tuttle³, Stephen Tong², Anne Ammerdorffer⁴, A Metin Gülmezoglu⁴, Joshua P Vogel^{5

6}

Affiliations

¹ Maternal, Child and Adolescent Health Program, Burnet Institute, 85 Commercial Road, Melbourne, VIC, 3004, Australia. [email protected].
² Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Australia.
³ Policy Cures Research, Sydney, Australia.
⁴ Concept Foundation, Geneva, Switzerland.
⁵ Maternal, Child and Adolescent Health Program, Burnet Institute, 85 Commercial Road, Melbourne, VIC, 3004, Australia.
⁶ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Abstract

Background: The Accelerating Innovation for Mothers (AIM) project established a database of candidate medicines in research and development (R&D) between 2000 and 2021 for five pregnancy-related conditions, including pre-eclampsia. In parallel, we published target product profiles (TPPs) that describe optimal characteristics of medicines for use in preventing/treating pre-eclampsia. The study objective was to use systematic double screening and extraction to identify all candidate medicines being investigated for pre-eclampsia prevention/treatment and rank their potential based on the TPPs.

Methods: Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched (Jan-May 2021). The AIM database was screened for all candidates being investigated for pre-eclampsia. Candidates in clinical development were evaluated against nine prespecified criteria from TPPs identified as key for wide-scale implementation, and classified as high, medium or low potential based on matching to the TPPs. Preclinical candidates were categorised by product type, archetype and medicine subclass.

Results: The AIM database identified 153 candidates for pre-eclampsia. Of the 87 candidates in clinical development, seven were classified as high potential (prevention: esomeprazole, L-arginine, chloroquine, vitamin D and metformin; treatment: sulfasalazine and metformin) and eight as medium potential (prevention: probiotic lactobacilli, dalteparin, selenium and omega-3 fatty acid; treatment: sulforaphane, pravastatin, rosuvastatin and vitamin B3). Sixty-six candidates were in preclinical development, the most common being amino acid/peptides, siRNA-based medicines and polyphenols.

Conclusions: This is a novel, evidence-informed approach to identifying promising candidates for pre-eclampsia prevention and treatment - a vital step in stimulating R&D of new medicines for pre-eclampsia suitable for real-world implementation.

Keywords: Chloroquine; Drug development; Esomeprazole; Hypertension; L-Arginine; Maternal medicine; Metformin; Pregnancy; Sulfasalazine; Vitamin D.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biological Products* / therapeutic use
Dietary Supplements
Female
Humans
Metformin* / therapeutic use
Pre-Eclampsia* / drug therapy
Pre-Eclampsia* / prevention & control
Pregnancy
Vitamin D

Substances

Biological Products
Vitamin D
Metformin