The 97% cure rate for the novel compound, ganaplacide/lumefantrine in a recent Phase 3 trial offers hope for continued progress rolling back malaria even as resistance to artemisinin combination therapies (ACT) escalates. 

A next-generation antimalarial drug GanLum (ganaplacide/lumefantrine, KLU156) slightly outperformed a standard of care Artemisinin Combination Therapy (ACT) in a recent Phase 3 trial – offering new hope that recent gains against malaria can be maintained and advanced despite growing parasite resistance to current treatments.  

The randomised controlled trial (RCT) involving over 1,600 participants across 12 Sub-Saharan African Countries demonstrated a +97% cure rate for GanLum, as compared to 94% for the ACT, Coartem©, in the control arm of the trial, said the pharma firm Novartis. The results were published Wednesday following an embargoed briefing at the annual conference of the American Society for Tropical Medicine and Health (ASTMH) in Toronto, including Novartis co-developer, Medicines for Malaria Venture (MMV), lead trial coordinator, Abdoulaye Djimdé, and ASTMH President, David Fidock. 

The trial is all the more significant insofar as it tested efficacy against malaria caused by the most deadly parasite, Plasmodium falciparum (P. falciparum).

P. falciparum is responsible for almost all malaria-related deaths worldwide. African countries bear the heaviest burden, accounting for an estimated 95% of the 597,000 malaria-related deaths globally in 2023.

After falling dramatically from 2000 to 2015, malaria deaths and infections, which mainly occur in children under 5 years old, have increased. The 2023 levels of 263 million cases and 597,000 deaths reflect the sharp rise seen since 2016 when there were 216 million malaria cases and 445,000 deaths.

“GanLum could represent the biggest advance in malaria treatment for decades,” declared  Djimdé, Professor of Parasitology and Mycology at the Bamako University of Science, Techniques and Technologies in Mali. Djimdé coordinates the West African Network for Clinical Trials of Antimalarial Drugs (WANECAM), which was a lead partner in the GanLum trial. The trial, which included 34 sites across West and Central Africa along with others in Zambia, Kenya, Uganda, Tanzanina, and one site in India, began in March 2024 and concluded in June 2025. 

“After the successful Phase 3 trial, we will submit the drug for regulatory approval as soon as possible,“ said George Jagoe, Executive Vice President at Medicines for Malaria Venture (MMV), the Geneva-based non-profit product development partnership. “We hope to see it within a year, year and a half, in the hands of countries and eventually in patients.” 

Initial regulatory approval is expected to be sought in Switzerland via Swissmedic. But the aim is to kickstart national regulatory procedures in the Sub-Saharan Africa region as well, added Vaidyanathan.

The drug would be made available on a ‘largely not-for-profit’ basis in low- and middle-income countries, MMV said, in accordance with agreements signed with Novartis.

The next-generation drug GanLum combines the novel non-artemisinin compound ganaplacide (KAF156), with an updated formulation of lumefantrine (LUM-SDF), also used in standard ACTs. Ganaplacide was initially identified by Novartis through high-throughput screening of 2.3 million compounds in San Diego, California, funded by MMV and the Wellcome Trust.

Together, the components target multiple stages of the malaria parasite’s life cycle and can prevent transmission. Ganaplacide disrupts the parasite’s internal protein transport system, which is essential for its survival inside red blood cells. It is also effective against the mature sexual stages of the parasite (gametocytes), as explained by Sujata Vaidyanathan, Head of the Global Health Development Unit at Novartis. 

This blocks them from spreading to other human hosts via mosquito bites. Meanwhile, lumefantrine prevents the parasite from re-emerging in the human’s body at a later stage.

Trial confirms efficacy and safety

The trial involved randomised testing of the GanLum against the control drug Coartem©, a gold standard for treatment,  on 1,688 adults and children weighing at least 10 kg and aged at least two years with acute, uncomplicated malaria, across 34 sites in the 12 African countries where it was tested.

The primary objective of the Phase 3 trial was to demonstrate that KLU156 is non-inferior to Coartem© (artemether-lumefantrine), as measured by the PCR-corrected cure rate on day 29 of treatment. 

According to data provided by Novartis, GanLum achieved an efficacy of 97.4% using the “estimand” framework. The current standard of care with ACTs has a rate of 94%. The “estimand” method is a conservative approach to results, required to support regulatory submissions, which considers patients that discontinue the study or for whom PCR data is missing at the time of the primary analysis to have failed the treatment.

Regarding the side effects, expert Djimdé said: “As with any drug, there are certain expected side effects. However, this was a randomised trial, and the safety profile is comparable to that of the reference compound. So it is absolutely fine to be put in the hands of patients.”

Hope in face of drug resistance and funding cuts

This new drug combination is a vital advance in the fight against malaria. Progress had recently stalled due to global health funding cuts and the conflict-linked displacement of many malaria-prone populations. In addition, extreme weather events caused by climate change have damaged public health infrastructure and enabled malaria parasites to spread to new regions.

The emergence of partial resistance to artemisinin-based combination therapies (ACTs), threatens to undo years of progress. According to the WHO, this could result in an additional 78 million malaria cases over five years in a business as usual scenario.

MMV’s Jagoe described reports of resistance in several countries in Central and Eastern Africa, such as Rwanda and Uganda, as “smoke signals’’, adding. “It is a huge relief that we can now think about a brighter future,“ he said. “We finally have a fire extinguisher ready.”

The intention is not to abandon artemisinin-based treatments, but rather to add an effective new weapon to the fight against malaria. 

Significantly, GanLum also targets mutations of the parasite that are markers of drug resistance.

Crucial step in long road toward elimination 

The experts presenting the Phase 3 trial results described tremendous excitement over the results – a crucial step forward in the fight against malaria. 

“I’m very, very excited, and very pleased to see the results of this GanLum trial”, said Jagoe from MMV.

However, after approval, the drug will still have to prove its efficacy in the field.

Challenges to overcome

And there are major challenges to overcome. The trial was initially designed to include children weighing over 5 kg and aged over two months. 

That is because infants and toddlers, especially those in the lowest weight category, typically have the highest mortality rates, particularly in areas with moderate to high transmission rates.

However, since reported prevalence is often lower, the age, and weight thresholds of the trial were increased in a pragmatic move to identify trial participants and accelerate the process of testing the new drug.

But the intention is to trial the drug on children between 5 and 10 kg in weight and 2 months and 2 years in age – as soon as it becomes feasible.

As a Novartis spokesperson explained in an interview with Health Policy Watch, “We are committed to supporting the youngest children.” 

Novartis recently received approval for Coartem Baby, a malaria drug designed for newborns and young infants, also co-developed with MMV.

See related story here. 

Ghanaian Newborns First to Get New Malaria Medication

While the road to a single-dose curative treatment for malaria, often referred to as the Holy Grail, remains elusive, GanLum also represents a step forward on that score. It is administered as a daily sachet of granules for three consecutive days. Standard antimalarial therapy with ACTs involves taking medication twice daily for three days.

This complex regimen is known to result in suboptimal patient adherence – wiith a third or more of patients failing to complete regimes in the real-world. This reduces the effectiveness of the drug and increases the likelihood of partial resistance.

A potential single-dose treatment, also unveiled at the ASTMH, could significantly improve adherence as well as fighting parasite resistance, its proponents say.  The single-dose treatment combining four known anti-malarials –  sulfadoxine, pyrimethamine, artesunate and pyronaridine (SPAP) — was trialed on 539 patients in Gabon with uncomplicated malaria, including children under the age of 10, as compared to another 442 people who received the standard ACT. Some 93% of patients who received the single dose cure were free of parasites after 28 days, as compared to 90% of those who received the standard ACT.  

“We found that our single-dose treatment was just as effective as the standard course that typically requires taking six doses spaced out over three days, which many patients never complete,” said Ghyslain Mombo-Ngoma, MD, PhD, lead author of the study and head of clinical operations at the Medical Research Center of Lambaréné, Gabon (known by its French acronym CERMEL).

Image Credits: Novartis, Health Policy Watch , Novartis , Munira Ismail_MSH, Peter Mgongo, WHO .