Malaria leads to nearly 600,000 deaths annually, but that figure was closer to 2 million a quarter century ago. Deaths spiked because the parasite that causes malaria developed resistance to drugs that were the standard of care for decades, said George Jagoe, executive vice president, access & product management, Medicines for Malaria Venture (MMV).
The tide turned against the disease with Coartem, a Novartis combination therapy that became the new standard of care for malaria infection following its initial regulatory approval in 1999. But in parts of Africa where this infectious disease is prevalent, Jagoe said there are now worrying “smoke signals” of resistance to artemisinin, one of the main components of Coartem. An experimental Novartis malaria drug that brings a new mechanism of action to malaria has pivotal clinical trial results showing cure rates surpassing the 90-95% recommended threshold of the World Health Organization. The data were presented Wednesday at the American Society of Tropical Medicine and Hygiene annual meeting in Toronto.
“The deaths that we saw, to be very clear, in the late 90s and early 2000s, like 2 million deaths a year, that was a direct function of drug failure,” Jagoe said, speaking during a briefing with journalists ahead of the data presentation. “And what gives us tremendous, the French word is ‘soulagement,’ it’s like a sense of relief, the sense of relief here literally comes from the fact that finally, in 2025, heading to a regulatory submission, we have a non-artemisinin drug.”
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Novartis said it plans to seek regulatory approvals for its malaria drug soon. It’s comprised of the novel molecule ganaplacide paired with the existing anti-malarial compound lumefantrine. Novartis refers to this combination by the shorthand “GanLum.” Lumefantrine is also the second part of the drug combination that makes up Coartem, whose artemisinin-derived component is artemether. While artemether kills the malaria-causing Plasmodium falciparum parasites quickly, the longer-acting effect of lumefantrine eliminates any parasites that were missed.
Ganaplacide was discovered and developed at Novartis’s San Diego labs, said Sujata Vaidyanathan, head of the company’s global health development unit. This drug works by disrupting the parasite’s internal protein transport system, which is essential for its survival inside a host’s red blood cells. The drug also acts on the parasite at the stage in its life cycle when it can be picked up by a mosquito that bites an infected host. Attacking the parasite at this stage helps stop disease transmission, Vaidyanathan said.
Novartis evaluated GanLum in a Phase 3 clinical trial that enrolled 1,688 adults and children with malaria across 34 sites in 12 African countries. The study drug, given as a sachet of granules once a day for three days, was tested alongside standard of care Coartem and compared against treatment with Coartem alone.
Results showed that the proportion of patients free from clinical symptoms and baseline parasites 28 days after starting treatment, corrected by excluding new infections, was 97.4% for GanLum and Coartem compared to 84% for standard of care Coartem. The proportion of patients free of clinical symptoms and any parasites 28 days after the start of treatment, regardless of whether a recurrence was due to resurgence or new infection, was 85.3% for GanLum and Coartem compared to 82.1% for Coartem alone. These results met the main goal of showing GanLum was non-inferior to standard of care. Abdoulaye Djimdé, professor of parasitology and mycology at University of Sciences Techniques and Technologies of Bamako, Mali, who was part of the GanLum clinical trials, said the safety profile of the study drug was comparable to Coartem and adverse events were generally consistent with underlying disease.
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While MMV welcomes the development of GanLum, that will not mean abandoning the family of medicines that includes Coartem, Jagoe said. These anti-malarial drugs still work. But he added that the fact that Kenya, Rwanda, and Uganda had enough resistant strains to allow a clinical trial is a signal that a new drug is needed.
“I would call it being ready, having a fire extinguisher in the back that you’re ready to use but maybe not necessarily deploying, versus the house catches on fire and you’ve got nothing,” Jagoe said.
David Fidock, professor of microbiology & immunology and medical sciences at Columbia University and president of the American Society of Tropical Medicine and Hygiene, said that following regulatory approvals, he thinks GanLum should be moved into multiple lines of therapy in the countries most at risk. He said that includes Rwanda, where an estimated 40-50% of parasites already have the mutation that makes them resistant to artemisinin therapies.
Vaidyanathan said Novartis will seek regulatory approval through the same Swissmedic path used for Coartem Baby, a formulation of Coartem developed for newborns and young infants that was approved by the Swiss drugs regulator over the summer. Novartis is also talking with regulators in Sub-Saharan Africa.
GanLum was developed by Novartis with the scientific and financial support from 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. Addition funding came from the German Aerospace Center and the U.K. Department of Health and Social Care.
Illustration by Novartis