Malaria is commonly spread to humans through the bite of an infected female Anopheles mosquito. — TNS
A new clinical trial from Scripps Research in La Jolla, California, United States, aims to make significant gains in the global fight against malaria by making a drug that has been around since the 1970s last longer.
Working with a contract drug manufacturing and testing firm in Britain, 25 to 30 healthy volunteers are starting to receive the first doses of a new drug that is a long-acting enhancement of atovaquone, which is part of a once-daily, malaria-prevention combination medication often prescribed to travellers.
Malaria is a potentially life-threatening disease found mostly in tropical countries, which is spread to humans by some types of mosquitoes.
Symptoms can include fever, chills, headache, fatigue, confusion, seizures and difficulty breathing.
Scripps Research’s Calibr-Skaggs Institute medicinal chemistry vice-president Dr Arnab Chatterjee said that chemists, including the institute’s medicinal chemistry director Dr Anil Gupta, used a “prodrug” approach.
This meant attaching an inert molecule to a cloned version of atovaquone that causes it to remain in muscle tissue after being injected, thus causing it to slowly enter the bloodstream.
Once in circulation, enzymes cut away the time-release chemical, setting atovaquone free to do its malaria-fighting work.
And that work, Dr Chatterjee said, is quite significant, effectively preventing malaria after the bite of an infected mosquito.
“It’s 99% efficacious,” he said.
The drug in its oral form must be taken daily and has been considered too expensive – especially in countries with fewer resources – to use in broad-based prevention campaigns.
But the long-acting version now entering testing shows promise of lasting about three months, which – if proved safe and effective in human trials – could provide a way to inoculate whole regions.
Going the injectable route would also be a more efficient use of atovaquone because less of the chemical is needed when it doesn’t need to be digested, as is the case with oral dosing.
“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,” Dr Chatterjee said.
“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.
“If you lived in an area with year-round malaria, like Thailand, you would need to take it every three months.”
The idea has already passed muster with an external authority.
Scripps Research is working with Medicines for Malaria Venture, a Swiss not-for-profit organisation that works to bring affordable drugs to places where malaria kills an estimated 600,000 people per year.
If the phase 1 clinical trials detect no serious side effects, broader trials to prove efficacy could start next year.
A similar technique is underway for the prevention of HIV (human immunodeficiency virus) infection.
In that effort, Scripps scientists are working with drug giant Merck to test a long-acting pro-drug injectable of two HIV drugs made by Merck and Gilead, which licensed the development candidate in January 2024 after it successfully navigated initial safety trials. – By Paul Sisson/The San Diego Union-Tribune/Tribune News Service
