Scientists at Scripps Research in La Jolla have launched a groundbreaking clinical trial to transform a decades-old malaria prevention drug into a long-acting injectable formulation, potentially revolutionizing global malaria control efforts.
The Phase 1 trial, involving 25-30 healthy volunteers in the United Kingdom, focuses on enhancing atovaquone, a component of the widely-prescribed malaria prevention medication Malarone. This development could address one of the major challenges in malaria prevention: the need for daily medication.
Innovative Drug Development Approach
The research team, led by Arnab Chatterjee, vice president of medicinal chemistry at Scripps Research's Calibr-Skaggs Institute, has employed an innovative "prodrug" strategy. "It's 99% efficacious," Chatterjee notes, describing the drug's effectiveness in preventing malaria after mosquito transmission.
The enhancement involves attaching an inert molecule to a cloned version of atovaquone, enabling the drug to remain in muscle tissue post-injection. This modification allows for slow release into the bloodstream, where enzymes eventually activate the malaria-fighting compound.
Strategic Advantages for Endemic Regions
The injectable format presents several advantages over the current oral medication:
- Extended Protection: A single injection could provide protection for approximately three months
- Cost Efficiency: Less active ingredient required compared to oral dosing
- Improved Accessibility: Potential for mass prevention campaigns in resource-limited settings
"This could be really powerful somewhere like Sahel [Africa], where there is a defined rainy season and a defined period of time when mosquitoes are present," explains Chatterjee. "You can basically use the rains to predict when you are going to need this and be able to give a large group of people a single shot that protects them for an entire year."
Partnership and Future Prospects
The project has gained support from Medicines for Malaria Venture, a Swiss non-profit organization dedicated to developing affordable antimalarial drugs. This partnership is crucial, considering malaria claims approximately 600,000 lives annually in affected regions.
Should the current Phase 1 safety trials prove successful, the research team anticipates initiating broader efficacy trials in 2026. The development parallels similar efforts in HIV prevention, where Scripps scientists are collaborating with Merck and Gilead on long-acting injectable preventive medications.
Regional Implementation Considerations
The application of this enhanced medication would vary by region:
- Seasonal transmission areas (like the Sahel): Annual single-dose protection
- Year-round transmission zones (such as Thailand): Quarterly dosing required
This advancement could particularly benefit regions where daily oral medication proves logistically challenging or cost-prohibitive, potentially transforming the landscape of malaria prevention in endemic areas.
