Introduction and Background of the Project

Introduction

Schistosomiasis, also known as bilharzia and endemic in 78 developing countries, is a chronic inflammatory neglected tropical disease caused by parasitic worms. The disease affects more than 206 million people, including 100 million children, globally. It is one of the most prevalent tropical diseases in the world after malaria, and represents an important health burden in developing countries, especially in Africa where more than 90% of the infections occur.

The current gold standard recommended treatment for schistosomiasis, praziquantel (PZQ), is available in oral tablets for adults and children, but the effective dose for children < 4 years is currently not known as pharmacokinetics or dose-finding clinical studies have never been systematically conducted in this age group until recently. In addition, a pediatric formulation of praziquantel that would be appropriate for preschool age children, infants and toddlers, and would permit accurate dosing and enhanced compliance in these patients is non-existent and highly needed. The development of a new pediatric formulation of praziquantel is to be seen in the context of the WHO’s 2020 Roadmap and with respect to the initiative of “Uniting to combat Neglected Tropical Diseases” under which the global community agreed on control and elimination of schistosomiasis.

Project objective 

The Pediatric Praziquantel Consortium is an international not-for-profit partnership that aims to reduce the global disease burden of schistosomiasis by addressing the medical need of infected preschool-age children. Its mission is to develop, register and provide access to a suitable pediatric praziquantel formulation for treating schistosomiasis in this age group. The pediatric formulation under investigation has been designed to be smaller, exhibit an improved palatability and be orally dispersible compared to the current commercial formulation.

Project design 

The Consortium was established in July 2012 by Merck KGaA, Darmstadt, Germany (Merck KGaA), Astellas Pharma Inc. (Astellas), Swiss Tropical and Public Health Institute (Swiss TPH) and Lygature (formerly TI Pharma). At the beginning of 2014, Farmanguinhos and Simcyp, a Certara company, joined the Consortium as full partners. The Schistosomiasis Control Initiative (SCI) joined in 2016. At the end of 2017 Simcyp completed all its tasks around PK modeling and left the Consortium. In Jan 2018 Université Félix Houphouët Boigny (UFHB) and Kenya Medical Research Institute (KEMRI) joined the consortium as new partners. Since the start, all partners have been efficiently working together to progress the project and achieve the pre-clinical, clinical phase I-III and registration objectives.

All partners are bound by a Consortium agreement, which arranges their roles and responsibilities and includes a formal governance structure with a Consortium Board as the highest decision-making body, and Lygature as independent Coordinator. An external expert panel is called by the Consortium prior to each clinical development stage to provide an independent evaluation of the project. The partners have formed a core project team, led by Merck KGaA, comprising one representative of each partner and/or expertise area that meets every month. The core project team is supported by various subteams focusing on specific technical and operational aspects to implement the consortium’s program.

How can your partnership (project) address global health challenges?

In order to tackle the important public health problem of schistosomiasis, the non-profit Pediatric Praziquantel Consortium has been formed in July 2012 to develop a pediatric formulation of praziquantel. The project will contribute to the overall goal of control and elimination of schistosomiasis by developing a product urgently required for the treatment of preschool-age children, infants and toddlers, a population that is currently being considered by WHO to be included in treatment campaigns. The development and registration of a new pediatric formulation of praziquantel is regarded by the Consortium as a cornerstone to fulfill the 2020 WHO commitment to address the health burden that schistosomiasis represents and the importance of controlling disease-related morbidities. To achieve this commitment, several measures need to be integrated among which making chemotherapy treatment available to all age groups is an important part of.

What sort of innovation are you bringing in your project?

The Pediatric Praziquantel Consortium has developed and optimized pediatric orodispersible tablet (ODT) formulations of the enantiopure R-(-)-PZQ and racemate PZQ (back up) that will permit preschool-age children to be targeted for treatment thus closing the major treatment gap mentioned above. The target was to have a new ODT formulation that preferably contains the enantiopure R-(-)-praziquantel (L-PZQ ODT), since the schistosomicidal activity arises only from R-(-)-praziquantel, which has also been reported to be less bitter than racemate PZQ. Based on the outcome of the Phase I program and discussions with key stakeholders, including WHO PQP and WHO NTD, the Consortium included both formulations in the Phase II trial in children (age 3 months to 6 years) infected with S. mansoni in Cote d’Ivoire. Data from the Phase II pediatric trial (2-6 years) led to the selection of the L-PZQ ODT formulation at a dose of 50 mg/kg to be pursued for the phase III trial, the current stage of the development program.

Role and Responsibility of Each Partner

Merck KGaA (Darmstadt, Germany) leads the program and brings expertise and support related to praziquantel, including resources from different areas (drug product manufacturing, pre-clinical, clinical, regulatory) needed for clinical development & registration and to efficiently execute the project. Astellas contributes by providing its innovative pharmaceutical technologies in the area of pediatric drug formulation development as well as clinical development in children. Swiss TPH brings extensive experience in helminths biological and pharmacological research, epidemiology and clinical research in endemic regions. The governance is facilitated by Lygature, a Dutch non-profit organization and independent party with an extensive portfolio of international public-private partnerships in drug research and development, including in the area of neglected diseases. Farmanguinhos, the federal governmental pharmaceutical laboratory of the Fiocruz Foundation in Brazil, brings unique expertise to produce and distribute the new pediatric formulations product in endemic countries. KEMRI and UFHB will provide expertise on local disease epidemiology and clinical care, considered key elements of the future access strategy. Finally, SCI provides the necessary expertise to define and execute the access strategy and plan as well as to initiate and implement NTD control and elimination programs in Sub-Saharan Africa.

Others (including references if necessary)

For more detailed information on the Pediatric Praziquantel Consortium, the project team and the development program, please feel free to visit the Consortium website:

www.pediatricpraziquantelconsortium.org.

To receive regular updates on the progress and activities of the program, feel free to sign-up for the bi-annual Consortium Newsletter:

http://www.pediatricpraziquantelconsortium.org/nieuwsbrief.html

Final Report

1. Project objective

The Pediatric Praziquantel Consortium is a global non-profit partnership committed to reducing schistosomiasis in preschool-age children by developing and delivering a child-friendly praziquantel formulation, called arpraziquantel. Since 2012, partners have advanced through pre-clinical and clinical phases I–III. Project G2018-210 focused on validating the L-praziquantel drug substance manufacturing process in China, and drug product manufacturing process in Brazil, fulfilling EMA regulatory requirements, and preparing filings for endemic countries. The Consortium also worked with the WHO Neglected Tropical Diseases team to update its Access & Delivery plan and ensure future availability of arpraziquantel.

2. Project design

The Consortium operates through a transparent, agile governance model coordinated by Lygature (Netherlands). Merck (Germany) led the drug substance program, optimized Astellas (Japan)’ arpraziquantel formulation, and transferred manufacturing to Farmanguinhos (Brazil) for upscaling and supply. The pivotal Phase III trial was delivered through strong in-country partners—KEMRI (Kenya) and UFHB (Côte d’Ivoire)—with Swiss TPH overseeing trial management and Merck as sponsor (Project G2016-110). Unlimit Health (UK), with Swiss TPH and Lygature, led access planning, launching the ADOPT program in 2021. Collaboration was reinforced by WHO engagement and expert panels, ensuring alignment across clinical, regulatory, and access strategies (Project G2020-102).

3. Results, lessons learned

The Consortium successfully completed the development and initial registration steps for arpraziquantel, a pediatric dispersible formulation of L-praziquantel to treat schistosomiasis in preschool-aged children.

Merck validated the drug substance (L-praziquantel) process at commercial scale in China. It also completed the drug product technology transfer to Farmanguinhos in Brazil, which subsequently upscaled and produced the full-scale drug product batches that passed process performance qualification, enabling initial product supply.

Regulatory milestones were achieved, including the arpraziquantel regulatory file submission by Merck to the European Medicines Agency (EMA) under the EU-M4all procedure in 2023. EMA issued a positive scientific opinion, leading to arpraziquantel’s inclusion on the WHO list of prequalified medicines in 2024. Regulatory dossiers have subsequently been submitted in Uganda, Tanzania, Kenya, Côte d’Ivoire and Senegal, with Tanzania granting approval in August 2025. In parallel, regulatory submission to Brazilian’s medicine regulatory agency (called ANVISA) of arpraziquantel under the responsibility by Farmanguinhos, with support from Merck, was done in October 2024. Conclusion of dossier evaluation by ANVISA with final decision is expected for first half of 2026.

The Consortium updated its Access & Delivery plan and launched the ADOPT implementation research program in 2021, supporting pilot access planning in Côte d’Ivoire, Kenya and Uganda. A major Consortium meeting in Côte d’Ivoire in July 2025 facilitated stakeholder engagement, including ministries of health, WHO, and Non-Governmental Organizations.

The Consortium’s experience highlights the importance of adaptive governance and cross-sector collaboration in global health innovation. A key lesson was the value of maintaining flexibility in clinical planning. When external factors halted the planned phase III trial in Zimbabwe, the Consortium swiftly reallocated resources and adjusted its strategy without compromising regulatory progress.

Technology transfer across continents required robust coordination and clear communication. Early engagement with regulatory authorities, especially EMA and WHO, proved critical in anticipating and addressing complex requirements, such as GMP/GCP inspections.

Finally, the project reinforced the need for sustainability planning beyond initial registration. By aligning manufacturing, regulatory, and access strategies from the outset, the Consortium has laid the groundwork for long-term impact and scalability.