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Defining the next generation of severe malaria treatment: a target product profile
Jane Achan1, Aïssata Barry2, Didier Leroy3
1Malaria Consortium, London, UK.
Insights
New treatments for severe malaria are needed due to artemisinin resistance. Defining a target product profile (TPP) guides the development of potent, combination therapies to preserve current treatments and improve patient outcomes.
Area of Science:
- Infectious Diseases
- Parasitology
- Pharmacology
Background:
- Severe malaria poses a significant threat, especially to young children in Africa.
- Artemisinin-based therapies are effective but face widespread resistance, necessitating new treatment strategies.
- Emerging resistance in various regions underscores the urgent need for novel severe malaria treatments.
Purpose of the Study:
- To define the target product profile (TPP) for new severe malaria treatments.
- To outline characteristics for new therapies that ensure efficacy and combat drug resistance.
- To guide community efforts in addressing potential clinical failures of current artemisinin-based therapies.
Main Methods:
- Focus on defining the ideal characteristics of new antimalarial drugs for severe malaria.
- Consideration of combination therapies to prevent drug resistance.
- Evaluation of development pathways, including using approved partner drugs and novel molecules.
Main Results:
- New treatments must be highly potent with rapid antiparasitic activity.
- Combination therapies are crucial to deter resistance selection and dissemination.
- Development should prioritize injectable or rectal formulations for diverse clinical settings.
Conclusions:
- Defining the TPP is essential for a coordinated response to potential treatment failures.
- Shorter-term strategies involve developing artemisinin-based combination therapies.
- Longer-term goals include developing entirely novel combination treatments for severe malaria.
Background:
Severe malaria is a life-threatening infection, particularly affecting children under the age of 5 years in Africa. Current treatment with parenteral artemisinin derivatives is highly efficacious. However, artemisinin partial resistance is widespread in Southeast Asia, resulting in delayed parasite clearance after therapy, and has emerged independently in South America, Oceania, and Africa. Hence, new treatments for severe malaria are needed, and it is prudent to define their characteristics now. This manuscript focuses on the target product profile (TPP) for new treatments for severe malaria. It also highlights preparedness when considering ways of protecting the utility of artemisinin-based therapies.
Target Product Profile:
Severe malaria treatments must be highly potent, with rapid onset of antiparasitic activity to clear the infection as quickly as possible to prevent complications. They should also have a low potential for drug resistance selection, given the high parasite burden in patients with severe malaria. Combination therapies are needed to deter resistance selection and dissemination. Partner drugs which are approved for uncomplicated malaria treatment would provide the most rapid development pathway for combinations, though new candidate molecules should be considered. Artemisinin combination approaches to severe malaria would extend the lifespan of current therapy, but ideally, completely novel, non-artemisinin-based combination therapies for severe malaria should be developed. These should be advanced to at least phase 2 clinical trials, enabling rapid progression to patient use should current treatment fail clinically. New drug combinations for severe malaria should be available as injectable formulations for rapid and effective treatment, or as rectal formulations for pre-referral intervention in resource-limited settings.
Conclusion:
Defining the TPP is a key step to align responses across the community to proactively address the potential for clinical failure of artesunate in severe malaria. In the shorter term, artemisinin-based combination therapies should be developed using approved or novel drugs. In the longer term, novel combination treatments should be pursued. Thus, this TPP aims to direct efforts to preserve the efficacy of existing treatments while improving care and outcomes for individuals affected by this life-threatening disease.
