Ganaplacide/Lumefantrine

Novartis reported positive late-stage findings for its investigational antimalarial treatment KLU156 (ganaplacide/lumefantrine, or GanLum), with the non-artemisinin combination meeting its key goal of non-inferiority to the standard of care Coartem (artemether/lumefantrine) in patients with acute, uncomplicated malaria due to Plasmodium falciparum.According to the company, the therapy pairs ganaplacide — an imidazolopiperazine class compound that disrupts the parasite's internal protein transport systems essential for its survival in host red blood cells — with a new once-daily formulation of lumefantrine. An earlier Phase II study in 524 participants had met its primary endpoint, showing efficacy of the combination in adults and children.Highlighting the threat of drug-resistant parasites, Novartis’ Chief Medical Officer Shreeram Aradhye, said “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.”The Phase III KALUMA trial — conducted in partnership with the WANECAM 2 consortium with financial support from the EU — enrolled 1,688 adults and children weighing ≥10 kg with P. falciparum infection across 12 African countries. Patients were randomised to receive either GanLum granules once daily or Coartem twice-daily for three days. Cure rate was the proportion of patients without clinical symptoms or parasites 28 days after treatment initiation, regardless of whether recurrence stemmed from recrudescence or new infection.The findings, presented Wednesday at the American Society of Tropical Medicine and Hygiene annual meeting, showed the study’s primary endpoint was met, with GanLum achieving a non-inferior PCR-corrected cure rate of 97.4% using an estimand framework against Coartem’s 94.0%, equating to cure rates of 99.2% and 96.7% respectively, under conventional per protocol analysis.Additional analyses demonstrated high efficacy of GanLum against mutant malaria parasites associated with partial drug resistance, as well as rapid response against mature gametocytes responsible for onward transmission. Meanwhile, the experimental combination’s safety profile matched the standard of care, with adverse events consistent with malaria itself.Granted Fast Track and Orphan Drug Designations by the FDA in 2022, Novartis plans to seek regulatory approvals for GanLum at the earliest.