Recognising World Pre-eclampsia Day

Today we recognise World Pre-eclampsia Day, a day to raise awareness of one the leading causes of maternal and newborn mortality worldwide.

Every year, pre-eclampsia and eclampsia result in up to 50,000 maternal deaths and 500,000 foetal deaths.?Women in low- and middle-income countries are seven times more likely to develop pre-eclampsia than women in high-income countries, with rates as high as 16.7% in parts of Africa.?Better medicines and diagnostics are needed to prevent and treat this life-threatening condition.?Currently only one medicine exists – magnesium sulphate – and only to prevent and treat seizures associated with severe pre-eclampsia/eclampsia.

The need for medicines to treat and prevent

Magnesium sulphate is used for both prevention and treatment of eclamptic seizures.

However, there are no currently available options to effectively prevent the initial development of pre-eclampsia. Nor are there alternatives to manage it at early or late-stage beyond monitoring and magnesium sulphate, which while effective, can have dosing limitations in low-resource settings where the recommended 24-hour regimen may not be feasible. As the only definitive treatment is delivery of the baby, new and better medicines are urgently needed.

What’s in the medicines pipeline?

As part of the Accelerating Innovation for Mothers project – led by the Concept Foundation in partnership with Policy Cures Research and Burnet Institute, we curated a unique maternal health medicines pipeline database of drugs, biologics, and dietary supplements investigated or used at any point in the past 20 years (2000-2021) for five priority pregnancy-related conditions, including pre-eclampsia/eclampsia.

We found 153 unique medicines investigated or used for pre-eclampsia and eclampsia since 2000.

The vast majority were repurposed drugs, and dominated by preclinical and early stage R&D, with a number inactive.

Read the detailed analysis in our landscape report.

What medicine R&D should we prioritize?

The Accelerating Innovation for Mothers project also developed the first target product profiles (TPPs) for pre-eclampsia and eclampsia medicines. ?

TPPs are a recognised strategy to promote R&D of innovative or improved medicines or tools, describing the ideal characteristics of a product to treat, prevent or identify a disease.

We matched our TPPs for preeclampsia/eclampsia to the candidates we identified in the pipeline?to assess their potential. Of the 87 candidates in clinical development, we found seven had high potential and eight had medium potential to meet the needs for innovative pre-eclampsia and eclampsia medicines.

Diagnostics are needed too

Pre-eclampsia and eclampsia have a large spectrum of symptoms and clinical features, making diagnosis extremely challenging. Early signs include high blood pressure and proteinuria (protein in the urine), and these are the focus of most current clinical screening practices. The exact cause of pre-eclampsia remains unclear and there are no completely reliable rapid tests for prediction and early diagnosis.

The exact cause of pre-eclampsia remains unclear and there are no completely reliable rapid tests for prediction and early diagnosis.

Several tests, mainly based on biomarkers (like proteins in urine and blood vessel markers), have been developed for use alone or in combination for risk prediction or diagnosis. They are intended to assist the clinical judgment of healthcare providers. However, none of these have yet been widely accepted into clinical practice globally.

The Accelerating Innovations for Mothers project is currently working on a database of all diagnostic tests under investigation or in use for pre-eclampsia and eclampsia, alongside a TPP, to drive progress in this space.

Data will be available from September 2023.

Looking to the future

Researchers across the world are developing new innovations to detect, prevent and treat pre-eclampsia and eclampsia. A few are highlighted below.

• A new, nanoparticle-based diagnostic tool for pre-eclampsia has recently been clinical tested by researchers in the University of Technology Sydney (UTS). The test is a strip-based lateral flow assay, similar to rapid antigen tests used for COVID-19, that utilises innovative nanoparticle-based technology to detect two novel proteins in the blood plasma of women with pre-eclampsia. The highly sensitive test could be performed as the bedside with a fingerpick with results in as little as 15 minutes, meaning the diagnostic could be used in low-resource settings at a low cost.

• New research has shown that administering extended-release nifedipine, a blood pressure-lowering medication, daily throughout the labour and delivery process can prevent the need for intravenous (IV) medication during labour and delivery, avoiding serious maternal and foetal complications.

• A study by researchers at Cedars-Sinai Medical Center in Los Angeles have identified a blood test that can predict with over 90% accuracy whether a pregnant woman would develop pre-eclampsia with severe features or not. The test compares the ratio of two proteins that are involved in the blood vessel development in the placenta and would help inform clinical care decisions.

• Early preclinical studies by the University of Pennsylvania have developed a nanoparticle-based therapeutic containing mRNA that can be delivered to the placenta to treat the root cause of pre-eclampsia. The study in mice showed the IV administered mRNA therapeutic dilates the blood vessels to restore blood pressure, treating pre-eclampsia.

• Esomeprazole and metformin are promising candidates to treat pre-eclampsia. Clinical trials evaluating these treatments were conducted in South Africa by researchers at Mercy Hospital for Women, University of Melbourne and University of Stellenbosch.

• Concept Foundation and MirZyme Therapeutics have recently partnered to accelerate the development of new medicines and implement innovative products

We need funding to move research forward

The G-FINDER survey finds that from 2018 to 2021, just $101m was directed to pre-eclampsia and eclampsia R&D, split across basic research to understand the cause of the disorder, drugs to prevent and treat, and diagnostics to identify cases.

The US NIH represents the largest funder, with their investment totalling $68m across 2018-2021. Most of this ($47m) was for basic research, followed by $17m for medicines.

Collectively, industry is the second largest funder of pre-eclampsia and eclampsia R&D, contributing $12m across 2018-2021, almost all for the development of medicines.?

Policy Cures Research will publish the next edition of the G-FINDER sexual & reproductive health report in September 2023. Sign up here to receive it in your inbox.