Geneva – The Medicines Patent Pool (MPP) today announced the signing of a memorandum of understanding (MoU) with Ferring Pharmaceuticals that includes a conditional licence agreement for heat-stable carbetocin (HSC). The MoU aims to support expanded access to HSC and is aligned with wider efforts of Unitaid, Ferring and other organisations to reduce maternal mortality.

HSC is a proprietary formulation of carbetocin – an oxytocin analogue – currently indicated for the prevention of postpartum haemorrhage (PPH) after vaginal and caesarean births. HSC is a WHO pre-qualified medicine. According to the World Health Organization (WHO), around 70,000 deaths[1] each year are attributed to PPH, with over 90%[2] occurring in low- and lower-middle income countries (L&LMICs). Most of these deaths are preventable with timely access to safe and effective interventions[3]. However, the current standard of care for PPH prevention and treatment – oxytocin – needs to be stored between 2 and 8°C to maintain its effectiveness. In many L&LMICs, access to sustained cold-chain transportation and storage is not readily available[4] and the quality of oxytocin is variable[5]. Unlike oxytocin, HSC can be stored at up to 30 degrees Celsius for 48 months, making it a product that is well adapted for these settings[6] . A randomised controlled trial – the REACH trial – to evaluate HSC as a treatment for PPH is starting in 2024. The REACH treatment trial is sponsored by WHO’s Special Programme of Research, Development and Research Training in Human Reproduction (HRP) and funded by Unitaid, with additional support from MSD for Mothers and in-kind support from Ferring.

The MoU with MPP sets out the circumstances in which Ferring will grant a non-exclusive, non-transferable, royalty-free licence of Ferring’s patents and know-how covering HSC to MPP for MPP to enter into sublicences in respect of the registration, manufacture and supply of HSC to the public sector of target countries. These countries include all L&LMICs, per the World Bank Classification, and upper middle-income countries where the maternal mortality ratios are higher than 140 per 100,000 live births, the capability to maintain cold chain is an issue, and/or where price represents a barrier to access.

The licence and the right to grant a sublicence will be triggered if and when three criteria are met. These are:

1. HSC for the treatment of PPH is included in relevant WHO guidelines on PPH;
2. At least one stringent regulatory authority (SRA) has approved an extension of the HSC product label to include PPH treatment; and
3. Confirmed orders of HSC by Ferring and/or its authorised distributors to the public sector of the target countries reach a threshold of ten million ampoules per year.

Ferring and MSD for Mothers started to collaborate with WHO/HRP in 2013 through a public private partnership, to fund and execute the CHAMPION trial. The trial evaluated HSC for the prevention of PPH after vaginal birth. Following the positive results, Ferring’s HSC integrated into WHO’s normative policies and registered by Swissmedic for the prevention of PPH after vaginal and caesarean births. It is now registered for the prevention of PPH in 18 L&LMICs, and further registrations are being pursued by Ferring.

[1] World Health Organization. A Roadmap to Combat Postpartum Haemorrhage between 2023 and 2030. 2023. Available at https://iris.who.int/bitstream/handle/10665/373221/9789240081802-eng.pdf?sequence=1 Accessed January 2024

[2] World Health Organization. Maternal Mortality. 2023. Available at: https://www.who.int/news-room/fact-sheets/detail/maternal-mortality Accessed January 2024

[3] World Health Organization. WHO recommendations: Uterotonics for the prevention of postpartum hemorrhage. 2018. Available at: https://apps.who.int/iris/bitstream/handle/10665/277283/WHO-RHR-18.34-eng.pdf Accessed January 2024

[4] Widmer M. et al. Heat-Stable Carbetocin versus Oxytocin to Prevent Hemorrhage after Vaginal Birth. N Engl J Med. 2018 Aug 23;379(8):743-752.

Torloni MR. et al. Quality of Oxytocin Available in Low and Middle- Income Countries: A Systematic Review of the Literature (Systematic Review on Quality of Oxytocin). BJOG: An International Journal of Obstetrics and Gynaecology 2016;123(13):2076-2086

[5] PubMed. Quality of oxytocin available in low- and middle-income countries: a systematic review of the literature. Available at https://pubmed.ncbi.nlm.nih.gov/27006180/. Accessed April 2024

[6] SmPC Leaflet Carbetocin Ferring sol for inj 100mcg/ml amp 10x 1ml English. 2020