The Swiss pharma company Novartis has announced results from its Phase III trial KALUMA.
The clinical trial for KLU156 (ganaplacide/lumefantrine, or GanLum) has met the primary endpoint of non-inferiority to the standard of care Coartem (artemether-lumefantrine).
The novel non-artemisinin antimalarial, which was developed with Medicines for Malaria Venture (MMV), met the study’s primary endpoint of non-inferiority to the current standard of care.
The treatment achieved a 97.4% PCR-corrected cure rate using an estimand framework, compared to 94.0% with standard of care.
This equates to cure rates of 99.2% and 96.7% respectively, based on conventional per-protocol analysis.
If approved, GanLum would represent the first major innovation in malaria treatment since 1999, with the potential to kill drug-resistant parasites and block transmission.
The findings come amid urgent calls to tackle the growing threat of antimalarial drug resistance in Africa. Data were presented at the American Society of Tropical Medicine and Hygiene annual meeting 2025.
The study
The trial studied 1688 adults and children across 34 sites in 12 African countries, with GanLum given as a sachet of granules once a day for three days.
Additional analysis indicated the treatment was highly effective against mutant malaria parasites associated with partial drug resistance.
The treatment was also found to have a rapid response against mature gametocytes, the sexual stage of the parasite’s lifecycle responsible for onward transmission.
The findings come amid urgent calls to tackle the growing threat of antimalarial drug resistance in Africa. Data were presented at the American Society of Tropical Medicine and Hygiene annual meeting 2025.
“GanLum could represent the biggest advance in malaria treatment for decades, with high efficacy against multiple forms of the parasite as well as the ability to kill mutant strains that are showing signs of resistance to current medicines,” said Dr Abdoulaye Djimdé, Professor of Parasitology and Mycology at the University of Science, Techniques and Technologies of Bamako, Mali.
“Drug resistance is a growing threat to Africa, so new treatment options can’t come a moment too soon.”
GanLum
GanLum is a combination of two compounds, attacking the malaria parasite on multiple fronts: ganaplacide and lumefantrine.
The novel ingredient in GanLum, ganaplacide, has an entirely new mechanism of action, discovered after screening 2.3m molecules.
It is combined with a new once-daily formulation of existing antimalarial lumefantrine, a longer-acting treatment.
Ganaplacide is understood to work by disrupting the parasite’s internal protein transport systems, which are essential for its survival inside red blood cells.
It belongs to a class of compounds called imidazolopiperazines, first identified as potential antimalarials after a groundbreaking screen of 2.3m molecules to find drug candidates at Novartis labs in San Diego, California.
“Drug-resistant parasites threaten the efficacy of medicines that have helped to control malaria for decades,” said Dr Shreeram Aradhye, President, Development and Chief Medical Officer, Novartis.
“Together with our partners, we’ve gone further to develop a new class of antimalarial with an entirely new mechanism of action, which has the potential to both treat the disease and block transmission."
"We look forward to working with health authorities to bring this innovation to patients as soon as possible, helping close a critical gap in malaria care for those who need it most.”
Novartis plans to seek regulatory approvals from health authorities for GanLum as soon as possible.
The combination therapy was granted Fast Track Designation and Orphan Drug Designation by the US Food and Drug Administration in 2022.
If authorised by regulators, GanLum would represent the first major innovation in malaria treatment since artemisinin-based combination therapies, the current gold standard treatments, were introduced more than 25 years ago.
The treatment was developed by Novartis with the scientific and financial support of MMV and within the framework of the WANECAM2 consortium, which is funded by the European & Developing Countries Clinical Trials Partnership Programme supported by the European Union, with co-funding from the German Aerospace Center and the UK Department of Health and Social Care.
“Antimalarial drug resistance is a ticking clock — without action today, lives will be lost,” said Dr Martin Fitchet, CEO of MMV.
“GanLum’s Phase III results are a key step towards a new tool to help stay ahead of resistance."
"Working with Novartis and our partners, we’re committed to turning this promise into impact.”