Researchers have moved a step closer to making a new, simpler medication to treat kala-azar, a neglected disease that sickens about 4,000 Kenyans every year.
They said the development of the new oral drug has entered Phase II.
A Phase II trial tests the candidate drug’s safety and whether it works sufficiently well to warrant further investigation.
The developers, the Nairobi-based not-for-profit Drugs for Neglected Diseases initiative (DNDi) and its partners, described the proposed treatment as “safer, simpler and patient-friendly”.
But even if the proposed treatment is found to work, it will not be available soon.
Phase II trials often last as long as two years, while Phase III trials may last as long as four or five years. Phase IV trials may last for several years while researchers assess the effects of a drug after it has been approved.
Also known as kala-azar, visceral leishmaniasis is the world’s deadliest parasitic killer after malaria.
It causes fever, weight loss, spleen and liver enlargement, and, if not treated, death.
It is transmitted by the bite of infected sand flies, found in Turkana, West Pokot, Baringo, Isiolo, Baringo, Marsabit and Wajir.
The current treatment includes injections given at hospital daily for 17 days.
In a statement, DNDi said this treatment may also present rare but life-threatening side effects, including to the heart, liver and pancreas.
In contrast, the new molecule under study in Ethiopia, called LXE408, is administered in the form of oral pills and is expected to be safer than the current treatment.
“Our hope is that this new oral treatment will be efficacious and less toxic and can be given to patients at the primary healthcare level, close to their homes," Eleni Ayele, co-principal investigator of the clinical trial said.
"This would help them access treatment earlier, which could significantly decrease morbidity and transmission. If the trial is successful, it could go a long way toward enabling the sustainable elimination of this terrible disease.”
The molecule under investigation was discovered by Novartis. DNDi and Novartis initiated a collaboration and licence agreement in early 2020 to jointly develop it.
Novartis was responsible for completing pre-clinical development and a Phase I study. It is in charge of chemical manufacturing and control, and will drive regulatory submissions.
If trial results are positive and if the new treatment is approved for market use – Novartis has committed to distributing the drug on an affordable basis worldwide, with a focus on maximising access in endemic countries.
“We are moving towards a new generation of treatments for leishmaniasis. Finding new treatments is key if we want to sustainably eliminate visceral leishmaniasis in all parts of the world, including in African countries where the burden remains high. We need medical innovation,” Dr Fabiana Alves, director of the leishmaniasis programme at DNDi, said.
“We hope this new clinical trial will contribute to deliver better, patient-friendly, effective medicines that are accessible to everyone, with no exception.”
According to the Ministry of Health, at least 11 counties are constantly reporting transmission of the disease.
Kenya has been working to reduce the number of cases by at least 60 per cent and reduce the incidence by 50 per cent, according to the strategic plan for control of leishmaniasis 2021-25.
Kala-azar is classified as a neglected tropical disease and is caused by infection with leishmania parasites, which are spread by the bite of phlebotomine sand flies.
“For a very long time people were suffering from leishmaniasis, especially in the arid and semi-arid areas," former Head of Division of vector-borne and neglected tropical diseases at the Health ministry Sultani Matendechero said when he launched the strategic plan two years ago.
“But for some reason we were not able to detect and determine that it is leishmaniasis that is making people fall sick, killing them and making them unable to attend to their economic activities.”
The disease presents in two forms, visceral leishmaniasis and cutaneous leishmaniasis.
Cutaneous leishmaniasis is an immune-mediated skin pathology caused by the bite of sand flies infected with the leishmania parasite.
It is characterised by skin lesions, mainly ulcers on exposed parts of the body, leaving life-long scars and serious disability.
According to the World Health Organization, more than 90 per cent of new cases reported in 2019 occurred in 10 countries-Nepal, Iraq, Brazil, Eritrea, Ethiopia, India, Kenya, Somalia, South Sudan and Sudan.
The agency estimates that 50,000 to 90,000 new cases of VL occur worldwide each year, with 25 to 45 per cent reported to the WHO.
The treatment of leishmaniasis depends on the type of disease, concomitant infections, parasite species and geographic location.
It is treatable and curable, and requires an immunocompetent system.
In Kenya, the nationally recommended first-line treatment of VL is Paromomycin and Sodium Stibogluconate Combination Therapy, while AmBisome is the second line treatment for special VL cases as specified in the revised national guidelines.