A consortium of leading scientists and institutions in Africa and Europe has launched a project with funding from the European & Developing Countries Clinical Trials Partnership (EDCTP) aimed at delivering an improved formulation of a lifesaving treatment for cryptococcal meningitis, one of the leading causes of death in people with advanced HIV.
About 180,000 people a year, mostly in African countries, die from cryptococcal meningitis, a fungal infection that invades the lining of the brain. People with advanced HIV are particularly susceptible to it because they have weakened immune systems. Of the 180,000 annual deaths from cryptococcal meningitis, 135,000 are in sub-Saharan Africa.
“We are excited about collaborating with committed and outstanding research partners across two continents to develop a better adapted treatment for this devastating illness,” said Carol Ruffell, project leader of the 5FC Sustained Release (SR) development programme and director of the South Africa office of the non-profit research organisation, Drugs for Neglected Diseases initiative (DNDi), which is coordinating the consortium.
The consortium recently launched a Phase I study at FARMOVS, a clinical research facility in Bloemfontein, to develop a new formulation of the existing treatment, known as flucytosine (5FC). This new sustained release formulation (5FC SR) would only need to be administered twice a day instead of four times a day, as it is the case now.
“It would make a huge difference to give the patient flucytosine only twice a day, especially as we have so many patients to look after in our hospitals. It would help not having to administer the treatment in the middle of the night,” said Ida Oliphant, a nurse who treats cryptococcal meningitis patients at Khayelitsha Hospital in Cape Town. “Being able to take the treatment only every 12 hours would also encourage patients to complete the course once they are discharged from hospital.”
While undiagnosed and untreated fungal meningitis is fatal, more than 70% of people can survive if they receive early, safe and effective treatment with a combination of medicines including flucytosine.
The Phase I study will assess the comparative bioavailability of three candidate 5FC SR formulations in healthy study participants. The formulation is being developed so that it can be used as pellets, which can be taken with water, as well as via nasogastric tube. A Phase II study will follow in 2023 and 2024 in sites in Malawi and Tanzania, where cryptococcal meningitis patients will be enrolled in a randomised, controlled clinical trial to assess the 5FC SR formulation.
The consortium comprises a selected group of partners with an excellent track record of success delivering new tools and treatment strategies with an impact on public health: DNDi; FARMOVS; investigators from St George’s University of London; the National Institute for Medical Research (NIMR), Tanzania; the Lilongwe Medical Relief Fund Trust (LMRFT) in a partnership with the Kamuzu Central Hospital, Malawi; and the Luxembourg Institute of Health (LIH).
“Cryptococcal meningitis is one of the unacceptably under-studied and under-funded HIV related comorbidities, especially in sub-Saharan Africa. To address this critical gap in such vulnerable populations, EDCTP provides funding to improve treatment and access to essential drugs, as well as diagnosis of cryptococcal infections, as an integral part of healthcare systems. We are very encouraged by the start of this very promising 5FC HIV-Crypto consortium,” said Michael Makanga, executive director of European & Developing Countries Clinical Trials Partnership (EDCTP).
In tandem with the clinical trial work, the consortium will mobilise support for a combination of lifesaving treatments to be more widely available, particularly in African countries that are hard-hit by the disease.
Access to treatment for cryptococcal meningitis is urgently needed but is severely limited. The consortium will carry out focused work to support a strategy to increase access to the currently used immediate release formulation of flucytosine, and then, once developed, the new sustained release formulation. It will work with supporting partners, organisations and the CryptoMAG advocacy group to get flucytosine registered in more African countries, expand access to people who need it, and save lives.
Issued by the European & Developing Countries Clinical Trials Partnership (EDCTP)