Malaria remains an acute global health problem, causing hundreds of thousands of fatal cases every year, especially in the child population of Africa. For the past two decades, the standard treatment has been Artemisinin-based Combination Therapies (ACTs). However, the causative agent of malaria, Plasmodium falciparum, is showing increasing resistance to artemisinin. Against the backdrop of this critical resistance, the new combined drug from Novartis, KLU156, has proven in a large-scale clinical trial conducted in 12 African countries that its therapeutic efficacy is comparable to ACT treatment.
Antimicrobial resistance was first recorded in 2009 in the Thailand-Cambodia border region. Since then, mutations in the K13 gene have also spread to the African continent. The advantage of KLU156 is that it eradicated K13 mutants faster, thereby “protecting” lumefantrine (one of the drug components) from therapeutic failure.
Study Details:
The study, involving more than 1,600 patients, compared the efficacy of KLU156 to Coartem, a globally recognized ACT therapy. The strategic importance of the results is undeniable, as the trend of ACT resistance turns malaria into a difficult-to-treat disease. KLU156 represents a promising alternative that effectively eradicates parasites—especially resistant strains—and reduces transmission potential.
Researchers treated patients with a fixed, three-day protocol, using KLU156 for some and Coartem for others. The clinical data received: 99.2% of patients in the KLU156 group achieved a complete cure, compared to 96.7% in the Coartem group. “This is really music to my ears,” said Abdoulaye Djimde (University of Sciences, Techniques, and Technologies of Bamako), one of the leading scientists in the study.
It is also important that KLU156 more effectively eradicates gametocytes—the parasite stage transmitted by mosquitoes (Anopheles)—than Coartem. According to David Fidock, a specialist at Columbia University, this could help limit malaria transmission. Notably, in 2023 alone, 246 million cases and 569,000 fatal outcomes were recorded on the African continent.
How Does KLU156 Work?
Unlike artemisinin, which is derived from an ancient Chinese plant (wormwood), ganaplacide was identified as a result of synthetic, high-tech research. Novartis screened 2 million different chemical compounds under laboratory conditions to find a substance that would specifically destroy the malaria parasite. Ganaplacide disrupts protein synthesis by the parasite, which leads to its rapid eradication. KLU156 is a combined drug that provides a synergistic therapeutic effect with lumefantrine (Coartem’s partner).
Artemisinin-based Combination Therapies (ACTs) operate on a strictly defined pharmacological principle that involves a two-stage strategy. In the first stage, the fast-acting component, artemisinin, causes the primary and massive destruction of most parasites. In the second stage, the second “partner drug” ensures the complete eradication of the remaining parasites that survived the action of artemisinin.
Side Effects:
In the clinical trial, 20% of patients experienced vomiting (compared to 5% with Coartem), which also led to a high rate of early treatment discontinuation. Novartis attributes the problem to the drug’s bitter taste. The research centers partially overcame this challenge by mixing the medication with liquid. Intensive testing of taste improvement methods is currently underway.
Future Perspective
Debate is currently underway regarding the use of KLU156: Should it be kept as a backup therapy? Should its use be started immediately in regions with high resistance? Or should it be rotated with ACTs annually? The financial accessibility of the drug remains a critical factor—in response to this challenge, Novartis states that it plans to ensure non-commercial access.
Authorization for the drug is expected in the near future. “In a year, or a year and a half,” said George Jagoe, a representative of Medicines for Malaria Venture. This event represents a “sigh of relief” for global healthcare.
Diana Wirth, a specialist at Harvard University, calls this finding fundamental: “We have been waiting for this for a long time.”
This biotechnological breakthrough will radically transform malaria management and buy us time for an effective fight against resistance.
Source: Science
