So-called neglected tropical diseases are concentrated almost exclusively in impoverished populations in the developing world. Barely known in industrialized nations, they attract little public attention and research funding. One poignant example is schistosomiasis. Our aim is to help in providing urgent action to prevent and control these neglected diseases, as well as more familiar ones such as malaria.
Strategy for preventing and treating infectious diseases
Our strategy is to not only develop and provide medicines, but also to improve diagnosis, counter disease transmission, increase disease control and strengthen local health systems. We seek to improve healthcare in developing countries by creating novel and integrated health solutions for infectious diseases and by ensuring the sustainable implementation of these innovations, many of which are led by our Global Health Institute. Our Group-wide initiatives and programs particularly address the medical needs of women and children.
Our comprehensive Global Health portfolio includes the following programs:
- Development of a pediatric formulation for praziquantel to treat schistosomiasis in children under the age of six
- Development of a new active ingredient to treat and prevent malaria
- Screening of our compound library in search of potential new active ingredients to treat schistosomiasis and malaria
- Development of diagnostic kits for schistosomiasis and malaria
- Development of products and technologies to enhance prevention of disease infection and re-infection
In addition, we engage in activities that address bacterial infections and antimicrobial resistance, for example by developing assets for antibiotic quality and laboratory capacity to detect antimicrobial resistance, improving the use of antibiotics by healthcare providers and patients, and helping define industry-wide guidelines for the control of antibiotics.
Our fight against schistosomiasis
Schistosomiasis, also known as bilharzia, is one of the most prevalent parasitic diseases in Africa, placing a great burden on public health and the local economy. The disease affects over 200 million people worldwide, with more than 90% of cases occurring in Sub-Saharan Africa. Around 10% of those affected are preschool age children. An estimated 200,000 people die every year from the effects of schistosomiasis, such as liver and kidney infections, bladder cancer and blood loss.
In the 1970s, we partnered with Bayer to develop a medicine called praziquantel. Today, praziquantel remains the standard of care for the effective treatment of schistosomiasis around the world.
We have been partnering with the World Health Organization (WHO) since 2007, regularly providing them with donations of praziquantel tablets. Over time, we have built up a portfolio of pioneering R&D projects on schistosomiasis. These include:
- a new pediatric formulation of praziquantel to treat children under the age of six
- the screening of our proprietary compound library through a dedicated schistosomiasis drug discovery platform
- the development of innovative and highly sensitive schistosomiasis diagnostic methods
- the setup of approaches for vector control
- health education programs that help prevent transmission
Our fight against malaria
According to estimates by WHO, nearly half of the world’s population is at risk of malaria. More than 200 million cases of malaria and over 400,000 related deaths are recorded every year with 70% in children under five years of age. Around 90 different countries are affected by the disease, with approximately 90% of deaths occuring in Africa.
There is an urgent need for new products to overcome the problem of increasing drug resistance and to achieve the goal of complete eradication. Through our Malaria program, we are well positioned to help deliver integrated and sustainable health solutions against malaria (treatments, diagnostics, prevention methods) to endemic countries. In our efforts, we closely collaborate with a wide range of partners in both developed and developing countries.
Schistosomiasis: Over 900 million donated tablets
As part of our long partnership with the World Health Organization that dates back to 2007, we agreed to donate praziquantel tablets every year for distribution in African countries. This year, our donation program was expanded to include Burkina Faso, Niger, and Sierra Leone, and now covers a total of 46 countries. In 2018, we donated approximately 200 million tablets for distribution in 34 countries, and we keep our commitment by maintaining production capacities to a level sufficient for manufacturing up to 250 million tablets a year.
Schistosomiasis Health Education Project
We have been working with the NALA Foundation since launching the Schistosomiasis Health Education Project in 2017. Through this partnership, we are donating nearly € 300,000 over a period of three years to support the Federal Ministry of Health in Ethiopia in promoting the long-term behavioral change that is needed to help eliminate schistosomiasis and other neglected tropical diseases. The project targets a population of 850,000 in Bench Maji, a region in southwestern Ethiopia, with a focus on approximately 260,000 students in 290 schools and includes distribution of customized educational material and improving water sanitation and hygiene facilities through a community-based approach. In 2018, activities were launched in all 74 schools of the Bero and South Bench districts of the Bench Maji region, reaching almost 70,000 students in total. The goal for 2019 is to extend this model to two other districts.
Central platform in the battle against this parasitic disease
Since schistosomiasis is a complex disease, a coordinated, multi-sectoral approach is needed to combat it. We joined forces with international partners from various sectors to address the remaining gaps in the fight against this infection and initiated the Global Schistosomiasis Alliance (GSA) in 2014, to coordinate and increase the impact of our efforts. The founding members of the GSA include the Bill & Melinda Gates Foundation, the Schistosomiasis Control Initiative (SCI), the United States Agency for International Development (USAID) and World Vision International.
In 2018, the GSA acquired additional international stakeholders as new members. As well as organizing several conferences and key meetings, it took part in various projects aimed at driving local efforts to combat schistosomiasis. The GSA is also working to promote and support an international action plan to progress schistosomiasis control and eventually achieve elimination of the disease. The GSA continues with its efforts to raise awareness through campaigns such as #MakingSchistory, which began in 2017.
Partners in schistosomiasis research
The need for a more sensitive diagnostic is crucial in the fight against schistosomiasis. Since 2017, we have been collaborating with the Australian Institute of Tropical Health and Medicine at James Cook University in Townsville (Australia) and with the Baylor College of Medicine in Houston (United States) to research new biomarkers in order to develop diagnostic tools for schistosomiasis. A collaboration with the Bill and Melinda Gates Foundation and the Foundation for Innovative Diagnostics started in 2018, with the objective of developing innovative rapid diagnostic solutions for schistosomiasis.
Praziquantel is an effective and well tolerated drug, but it is not active against all development stages of the parasite. Research activities have continued in collaboration with many partners in developing and developed countries. This discovery work searches for new, long-lasting compounds to treat juvenile forms of the parasite, improve efficacy and prevent reinfections. One potential compound has been identified and is currently in the pre-clinical research phase. We also continued supporting academic research into a new genome editing method for vector control to combat schistosomiasis.
We have been fostering research and development as well as manufacturing capacities and know-how in endemic countries through collaboration with local academic and public institutions. We have been implementing a series of research programs on schistosomiasis involving African post-doctoral researchers. New initiatives and opportunities were also assessed to tackle female genital schistosomiasis and its impact on HIV/AIDS.
Consortium for the development of Pediatric Praziquantel Formulation
If left untreated at preschool-age, schistosomiasis can have long-term effects such as stunted growth and an impaired learning ability, causing chronic diseases like bladder cancer or genital schistosomiasis. Since July 2012, we have been working within the Pediatric Praziquantel Consortium, with representatives from both the public and private sector including funding organizations, with the goal of developing a pediatric formulation of praziquantel for all children under the age of six.
Following initial Phase I studies and a taste evaluation, we completed a Phase II study in Ivory Coast to assess the efficacy and safety of two different formulations for orodispersible tablets in schistosomiasis-infected children under the age of six. The results indicate that both formulations are well tolerated and confirmed one formulation for further development. The process for the active pharmaceutical ingredient has been developed and is being transferred to a contract manufacturing organization.
In 2018, two new partners joined the Consortium: the Kenya Medical Research Institute (KEMRI) and the Université Félix Houphouët-Boigny in Ivory Coast. Both will play an important role in implementing the Phase III trial, which is due to start in the first half of 2019. This trial comprises the confirmatory clinical study in schistosoma-infected preschool-age children and is co-funded by the Consortium, the European & Developing Countries Clinical Trials Partnership (EDCTP) and the Global Health Innovative Technology Fund (GHIT Fund). Regulatory submission is planned in 2020, and we expect the product to be available for launch in the first endemic countries in Africa in 2021.
Accurately diagnosing malaria
Malaria is hard to distinguish from other infections that cause a high fever. Reliable diagnostics are needed to correctly identify patients suffering from the disease so that the appropriate treatment can be administered to the right population. We have been working on a kit containing a novel malaria detection and typing test adaptable to the MUSE© cytometry platform. It aims to accurately diagnose malaria and measure the type of malaria parasite as well as the infection level. This malaria kit was launched for research use in 2018. At the end of 2018, we sold the underlying technology platform developed by our Life Science business sector to the U.S. laboratory supplier Luminex, which is now commercializing the diagnostic kit.
Enabling the treatment of children
We have been developing a new, innovative drug for the treatment of malaria since 2015. The new compound is intended to be developed as a single-dose combination treatment to treat and potentially prevent malaria in children. The Phase I study in healthy volunteers in Australia allowed the safety of the compound to be assessed, and a Phase Ib study provided data to support clinical proof of principle. These clinical activities have been supported through a grant by the Wellcome Trust, a biomedical research charity based in London.
The program is progressing towards the next phase, which entails the development of the asset in combination with another anti-malarial compound in acute uncomplicated malaria. The clinical development plan is also being defined with new clinical studies in patients to start in late 2019 or early 2020.
Developing new lead programs
Our strategic collaboration with the University of Cape Town in South Africa has led to the development of a new research and development platform. In 2018, this collaboration, including our collaboration with the Medicines for Malaria Venture, was extended to continue screening activities with the aim of identifying new therapeutic solutions for malaria while building research capacity in and for Africa. This program continues to leverage our proprietary chemical library of almost 100,000 compounds to identify new lead programs for the treatment of malaria, targeting liver-stage forms of the parasite and long-lasting compounds to improve post treatment prophylaxis. This program is co-funded by the German Federal Ministry of Education and Research.
A separate collaboration involving two research centers in Portugal, Instituto de Biologia Experimental e Tecnologica (iBET) and Instituto de Medicina Molecular (IMM), saw progression in the development of a new cell model of liver-stage malaria infection. This model could serve as a screening tool for novel anti-malaria drugs.
Preventing and controlling transmission
To help prevent the spread of malaria, we are working to improve access to insect repellent as a vector control method. Through internal and external collaborations, we are working towards demonstrating the efficacy of IR3535® against malaria in Africa. IR3535® is used in insect repellents for complementary prevention from vector borne diseases, such as malaria, dengue fever, Zika, Chikungunya, and Lyme disease. The repellent has the major advantage of being very safe for all age groups including children as well as for pregnant women and lactating mothers.
In 2018, we entered a partnership with the Infanta Malaria Prevention Foundation and with ASPIRx, a Ghanaian bio-pharmaceutical manufacturer. This supports the National Malaria Control Program of the Ghana Health Service by exploring development of solutions based on IR3535® for malaria prevention in vulnerable communities.
Addressing the global health challenge caused by antimicrobial resistance (AMR)
In order to address the growing emergency of increased bacterial resistance, we have been implementing new collaborative programs to assess the degree of resistance of identified bacterial pathogens. We also focus our efforts on the development of new technological platforms to speed up assessment of the type of infections. A Master’s program is currently being run at Makerere University (Uganda) where students are researching ways of tackling the three AMR areas of prevention, detection and management.