Novartis has reported positive top-line results from the phase 3 KALUMA trial evaluating KLU156 (ganaplacide/lumefantrine, or GanLum), its investigational malaria therapy.
KLU156 combines two compounds that target the malaria parasite by disrupting its internal protein-transport mechanisms, which are critical for its survival within infected red blood cells. The therapy is part of a new class of potential antimalarials, known as imidazolopiperazines, identified following a landmark high-throughput screen of 2.3 million molecules.
The therapy received Fast Track and Orphan Drug Designations from the US Food and Drug Administration (FDA) in 2022. If approved, it would represent the first major advance in malaria treatment in more than 25 years, following the introduction of artemisinin-based combination therapies.
The randomised, open-label, multicentre KALUMA study assessed the efficacy, safety and tolerability of KLU156 – a novel, non-artemisinin combination developed in partnership with Medicines for Malaria Venture (MMV) – against Coartem, the current standard of care for acute, uncomplicated malaria in adults and children caused by Plasmodium falciparum.
The trial met its primary endpoint, with KLU156 demonstrating non-inferiority to Coartem. The treatment achieved a 97.4% PCR-corrected cure rate using an estimated framework, corresponding to a 99.2% cure rate under conventional per-protocol analysis.
“Drug-resistant parasites threaten the efficacy of medicines that have helped to control malaria for decades,” said Shreeram Aradhye, President, Development and Chief Medical Officer, Novartis. “[This is]… a new class of antimalarial with an entirely new mechanism of action, which has the potential to both treat the disease and block transmission.”
Novartis said it intends to submit GanLum to regulatory and health authorities in the near future.