https://www.global-health-edctp3.europa.eu/results-and-insights/global-health-leaders/christian-happi_en

Entitled “Towards the First Non-artemisinin Combinations for falciparum Malaria: Phase 3 Results, Capacity Building in WANECAM 2 and Beyond”, this high-level scientific session brought together researchers, clinicians, institutional partners and global health stakeholders to discuss a major breakthrough in the fight against malaria.

Promising and Pivotal Phase 3 Results

The presenters shared the results of the Phase 3 clinical trial (KALUMA) of ganaplacide-lumefantrine SDF an innovative non-artemisinin-based therapeutic combination developed for the treatment of uncomplicated Plasmodium falciparum malaria.

The data demonstrated an efficacy rate exceeding 99%, confirming the strong potential of this new therapeutic combination. If approved, it could become the first fundamentally new antimalarial treatment without an artemisinin derivative in more than 25 years  a strategic breakthrough in a global context increasingly challenged by resistance to artemisinin derivatives.

This milestone represents a major scientific contribution from the WANECAM 2 consortium and highlights the excellence of clinical research conducted in partner countries.

WANECAM 2: A Lasting Impact on Capacity Building

Beyond the clinical results, the symposium also highlighted WANECAM 2’s achievements in strengthening research capacity across Africa.

The program has enabled:

• The training and mentorship of researchers and clinical research personnel;
• The development and modernization of research infrastructure meeting international standards;
• The strengthening of quality systems and Good Clinical Practice (GCP);
• The consolidation of a strong and sustainable regional scientific network.

These achievements constitute a structural legacy for biomedical research in Africa and reinforce the scientific autonomy of partner institutions.

A Key Step Toward the Future

The organization of this symposium at ASTMH 2025 marked a strategic milestone on the path toward the potential registration of a new non-artemisinin therapeutic combination for malaria.

Through this major scientific contribution, the WANECAM 2 consortium reaffirms its mission: advancing excellence in clinical research, sustainably strengthening local capacities, and making a decisive contribution to the global fight against malaria.

• Phase III trial for KLU156 (ganaplacide/lumefantrine, or GanLum), meets primary endpoint of non-inferiority to standard of care Coartem® (artemether-lumefantrine)
• Demonstrates PCR-corrected cure rate of 97.4% based on estimand method, equating to 99.2% under conventional per protocol analysis
• If approved, GanLum would represent first major innovation in malaria treatment since 1999, with potential to kill drug-resistant parasites and block transmission
• Novel ingredient in GanLum, ganaplacide, has entirely new mechanism of action, discovered after screening 2.3 million molecules
• Highlights Novartis long-term commitment to combating malaria, with more than 1.1 billion treatment courses of Coartem provided largely at no profit, and multiple novel antimalarial compounds in development

Basel, November 12, 2025 – Novartis today announced positive results from KALUMA, a Phase III study for new malaria treatment KLU156 (ganaplacide/lumefantrine, or GanLum). The novel non-artemisinin antimalarial, which was developed with Medicines for Malaria Venture (MMV), met the study’s primary endpoint of non-inferiority to the current standard of care. The treatment achieved a 97.4% PCR-corrected cure rate using an estimand framework, compared to 94.0% with standard of care. This equates to cure rates of 99.2% and 96.7% respectively based on conventional per protocol analysis.

The trial studied 1,720 adults and children across 34 sites in 12 African countries, with GanLum given as a sachet of granules once a day for three days. Additional analysis indicated the treatment was highly effective against mutant malaria parasites associated with partial drug resistance. The treatment was also found to have a rapid response against mature gametocytes, the sexual stage of the parasite’s lifecycle responsible for onward transmission. 

The findings come amid urgent calls to tackle the growing threat of antimalarial drug resistance in Africa.¹ Data were presented at the American Society of Tropical Medicine and Hygiene annual meeting 2025.²

“GanLum could represent the biggest advance in malaria treatment for decades, with high efficacy against multiple forms of the parasite as well as the ability to kill mutant strains that are showing signs of resistance to current medicines,” said Dr Abdoulaye Djimdé, Professor of Parasitology and Mycology at the University of Science, Techniques and Technologies of Bamako, Mali. “Drug resistance is a growing threat to Africa, so new treatment options can’t come a moment too soon.”

GanLum is a combination of two compounds, attacking the malaria parasite on multiple fronts: ganaplacide, a novel compound with an entirely new mechanism of action, and a new once-daily formulation of existing antimalarial lumefantrine, a longer-acting treatment. 

Ganaplacide is understood to work by disrupting the parasite’s internal protein transport systems, which are essential for its survival inside red blood cells.³ It belongs to a class of compounds called imidazolopiperazines, first identified as potential antimalarials after a groundbreaking screen of 2.3 million molecules to find drug candidates at Novartis labs in San Diego, California.

“Drug-resistant parasites threaten the efficacy of medicines that have helped to control malaria for decades,” said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. “Together with our partners, 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. We look forward to working with health authorities to bring this innovation to patients as soon as possible, helping close a critical gap in malaria care for those who need it most.”

Novartis plans to seek regulatory approvals from health authorities for GanLum as soon as possible. The combination therapy was granted Fast Track Designation and Orphan Drug Designation by the U.S. Food and Drug Administration in 2022. If authorized by regulators, GanLum would represent the first major innovation in malaria treatment since artemisinin-based combination therapies, the current gold standard treatments, were introduced more than 25 years ago.⁴

The treatment was developed by Novartis with the scientific and financial support of 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, with co-funding from the German Aerospace Center and the UK Department of Health and Social Care.

“Antimalarial drug resistance is a ticking clock—without action today, lives will be lost,” said Dr Martin Fitchet, CEO of MMV. “GanLum’s Phase III results are a key step towards a new tool to help stay ahead of resistance. Working with Novartis and our partners, we’re committed to turning this promise into impact.”

About the KALUMA study

The KALUMA (NCT05842954) study was a Phase III randomized, open-label, multicenter study to compare efficacy, safety and tolerability of GanLum with Coartem® (artemether-lumefantrine), the standard of care, in the treatment of acute, uncomplicated malaria due to Plasmodium falciparum in adults and children. The trial studied 1,720 adults and children ≥ 10kg with acute, uncomplicated malaria due to Plasmodium falciparum, with or without mixed plasmodium infection, at 34 trial sites across 12 countries in sub-Saharan Africa. Patients treated with GanLum were given a once-daily dose for three days, as a sachet of granules. The primary analysis was conducted using an ‘estimand’ approach, a conservative approach required to support regulatory submissions, which considers patients who discontinue the study or for whom PCR data is missing at the time of the primary analysis to have failed the treatment. A conventional ‘per protocol’ approach, which excludes these patients from the analysis, is the standard methodology used in clinical trials for antimalarials, and more easily allows for comparison to historical trials and other antimalarial drugs. The principal stratum estimand consisted of patients who took a complete course of study treatment (at least 80% of study medication) and took non-study treatment with antimalarial activity prior to day 29 only in case of recrudescence. Results found:

• GanLum was non-inferior to the standard of care, meeting its primary and key secondary endpoint.
• PCR-corrected adequate clinical and parasitological response at Day 29 (proportion of patients free from clinical symptoms and baseline parasites 28 days after the start of treatment, corrected by excluding new infections) was 97.4% for GanLum, compared to 94.0% with the standard of care. Under a conventional per protocol analysis, conducted post hoc, this represents a cure rate of 99.2%, compared to 96.7% with the standard of care.
• Uncorrected adequate clinical and parasitological response at Day 29 (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 recrudescence or new infection) was 85.3% for GanLum, compared to 82.1% for the standard of care.
• The safety profile was similar to standard of care and adverse events were generally consistent with the underlying disease.

About malaria 

Malaria is a life-threatening disease caused by a parasite and spread to humans by some types of mosquitoes. According to the most recent WHO data, there were 263 million cases of malaria and 597,000 deaths in 2023, almost all of them in Africa. Children under 5 years old accounted for about three in four malaria deaths in the region.⁵ 

About Novartis in malaria innovation 

Novartis has built the industry’s largest pipeline of treatments to control or eliminate malaria and neglected tropical diseases,⁶ backed by nearly USD 500 million in funding for global health R&D since 2021. This includes four new non-artemisinin antimalarial compounds with the potential to combat rising drug resistance. Novartis has delivered more than 1.1 billion treatment courses of its antimalarial Coartem since 1999, mostly at no profit, and earlier this year launched Coartem Baby, the first malaria treatment for newborns and young infants.

About MMV

MMV is a Swiss non-profit product development partnership. MMV works “end-to-end” to discover, develop and deliver affordable and accessible medicines to treat, prevent and eliminate malaria. Since 1999, over 1.3 billion people have benefited from MMV’s co-developed medicines. With malaria still killing 600,000 each year, MMV brings partners together to close the remaining gaps in antimalarial access and innovation.
For more information, visit www.mmv.org. Follow MMV on social media: X, LinkedIn, YouTube and Facebook 

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis 
Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach nearly 300 million people worldwide.

Reimagine medicine with us: Visit us at www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram.

References

1. Rosenthal, Philip J et al. The emergence of artemisinin partial resistance in Africa: how do we respond? The Lancet Infectious Diseases, Volume 24, Issue 9, e591 – e600.
2. Winnips, C., et al. KALUMA – A pivotal Phase III trial to evaluate the efficacy, safety and tolerability of the novel anti-malarial drug ganaplacide-lumefantrine (KLU156) in uncomplicated malaria, Presented at Annual Meeting of the American Society of Tropical Medicine and Hygiene, November 12, 2025.
3. LaMonte GM, et al. Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway. Nat Commun. 2020 Apr 14;11(1):1780; Brancucci NMB, et al. An all-in-one pipeline for the in vitro discovery and in vivo testing of Plasmodium falciparum malaria transmission blocking drugs. Nat Commun. 2025 Jul 25;16(1):6884; Gal IR, et al. Drug Interaction Studies of Cabamiquine:Ganaplacide Combination against Hepatic Plasmodium berghei. ACS Infect Dis. 2025 Jan 10;11(1):69-79.
4. Premji ZG. Coartem: the journey to the clinic. Malar J. 2009 Oct 12;8 Suppl 1(Suppl 1):S3.
5. WHO. Malaria.
6. Access to Medicine Foundation. Access to Medicine Index 2024.  

On August 22, 2025, in the gracious presence of Their Majesties the Emperor and Empress of Japan, Professor Abdoulaye Djimdé received the Fifth Hideyo Noguchi Africa Prize, presented by Prime Minister Ishiba during a solemn ceremony held in Tokyo.

Our warmest congratulations to Professor Abdoulaye Djimdé for this prestigious distinction, which celebrates African research and Mali’s scientific leadership.

Maiga, F.O., Wele, M., Toure, S.M. et al. Artemisinin-based combination therapy for uncomplicated Plasmodium falciparum malaria in Mali: a systematic review and meta-analysis.

Malar J 20, 356 (2021). https://doi.org/10.1186/s12936-021-03890-0

Camara, M.D., Zhou, Y., De Sousa, T.N. et al. Meta-analysis of the global distribution of clinically relevant CYP2C8 alleles and their inferred functional consequences. Hum Genomics 18, 40 (2024). https://doi.org/10.1186/s40246-024-00610-y

Camara MD, Zhou Y, Dara A, Tékété MM, Nóbrega de Sousa T, Sissoko S, Dembélé L, Ouologuem N, Hamidou Togo A, Alhousseini ML, Fofana B, Sagara I, Djimde AA, Gil PJ, Lauschke VM. 2024. Population-specific variations in KCNH2 predispose patients to delayed ventricular repolarization upon dihydroartemisinin-piperaquine therapy. Antimicrob Agents Chemother 68:e01390-23.

https://doi.org/10.1128/aac.01390-23

Roukayatou Omorou, Blanche Delabie, Adeline Lavoignat, Victorien Chaker, Guillaume Bonnot, Karim Traore, Anne-Lise Bienvenu, Stephane Picot. Nanoparticle tracking analysis of natural hemozoin from Plasmodium parasites,Acta Tropica, Volume 250, 2024,107105,ISSN 0001-706X, https://doi.org/10.1016/j. Actatropica.2023.107105

Bin Said, I., Kouakou, Y.I., Omorou, R. et al. Systematic review of Plasmodium knowlesi in Indonesia: a risk of emergence in the context of capital relocation to Borneo?. Parasites Vectors 15, 258 (2022). https://doi.org/10.1186/s13071-022-05375-8

Omorou, R., Bin Sa’id, I., Delves, M. et al. Protocols for Plasmodium gametocyte production in vitro: an integrative review and analysis. Parasites Vectors 15, 451 (2022).

https://doi.org/10.1186/s13071-022-05566-3

Kouakou, Y.I., Millet, A., Fromentin, E. et al. Pre-referral intranasal artesunate powder for cerebral malaria: a proof-of-concept study. Malar J 21, 291 (2022).

https://doi.org/10.1186/s12936-022-04309-0

Masters-WANECAM2

Hepatic and renal tolerances of the combinations artemisinin-based therapeutics in the treatment of  uncomplicated malaria in Bougoula-Hameau, Sikasso in Mali

Mr Kassim SANOGO, Master of Clinical Biology (defended on May 2022)

Evaluation de la prévalence du paludisme due aux différentes espèces plasmodiales rencontrées dans une zone hyper-endémique  à Kati Faladje, Mali.

Mr Siaka GOITA, Master of Parasitology and Medical entomology

(Defended on January 2023).

Evaluation of epidemiological parameters of malaria transmission on a WANECAM 2 site, Kolle, Mali.

Dr Bouran Sidibé, Master of Parasitology and Medical Entomology

 (Defended on June 2023)

Evaluation des paramètres paludométriques dans l’aire de santé de Bougoula-Hameau à Sikasso au Mali.

Mr Mohamed Lamine Alhousseini, Master of Parasitology and medical entomology (Defended on September 2023).

Scientifics communications-WANECAM2

Study of biological reference values in the research sites at the Abdou Moumouni University, Niger. EDCTP Forum 7-10 November 2023 Paris, France

In vivo study to monitor the sensitivity of Plasmodium falciparum and other species to

Pyronaridine-artesunate and Artemether-lumefantrine in Niger. Fofana B., BRAH S., Daou M., Togo AH., Bamadio A., Sagara I., Dicko A., Ouedraogo J.B., Adehossi E, Djimde A. (ASTMH 2023).

Clinical trial capacity building from scratch: the WANECAM 2 experience in Niamey, Niger

Abdoulaye Djimde, WANECAM 2 – University of Science, Techniques and Technologies of Bamako (Mali) 7-9 November 2023

Dama S, Niangaly H, Ouattara A, Sagara I, Sissoko S, Traore OB, Bamadio A, Dara N, Djimde M, Alhousseini ML, Goita S, Maiga H, Dara A, Doumbo OK, Djimde AA. Reduced ex vivo susceptibility of Plasmodium falciparum after oral artemether-lumefantrine treatment in Mali. Malar J. 2017 Feb 2;16(1):59. doi: 10.1186/s12936-017-1700-8. PMID: 28148267; PMCID: PMC5289056.

West African Network for Clinical Trials of Antimalarial Drugs (WANECAM). Pyronaridine-artesunate or dihydroartemisinin-piperaquine versus current first-line therapies for repeated treatment of uncomplicated malaria: a randomised, multicentre, open-label, longitudinal, controlled, phase 3b/4 trial. Lancet. 2018 Apr 7;391(10128):1378-1390. doi: 10.1016/S0140-6736(18)30291-5. Epub 2018 Mar 29. PMID: 29606364; PMCID: PMC5889791.

Funck-Brentano C, Ouologuem N, Duparc S, Felices M, Sirima SB, Sagara I, Soulama I, Ouedraogo JB, Beavogui AH, Borghini-Fuhrer I, Khan Y, Djimdé AA, Voiriot P. Evaluation of the effects on the QT-interval of 4 artemisinin-based combination therapies with a correction-free and heart rate-free method. Sci Rep. 2019 Jan 29;9(1):883. doi: 10.1038/s41598-018-37113-5. PMID: 30696921; PMCID: PMC6351684.

Compaoré YD, Zongo I, Somé AF, Barry N, Nikiéma F, Kaboré TN, Ouattara A, Kabré Z, Wermi K, Zongo M, Yerbanga RS, Sagara I, Djimdé A, Ouédraogo JB. Hepatic safety of repeated treatment with pyronaridine-artesunate versus artemether-lumefantrine in patients with uncomplicated malaria: a secondary analysis of the WANECAM 1 data from Bobo-Dioulasso, Burkina Faso. Malar J. 2021 Jan 29;20(1):64. doi: 10.1186/s12936-021-03593-6. PMID: 33514368; PMCID: PMC7847156.

Fofana B, Takala-Harrison S, Ouattara A, Sagara I, Togo AH, Diakité H, Keita M, Sanogo K, Touré S, Doumbo OK, Djimde AA. Differential Incidence of Malaria in Neighboring Villages in a High-Transmission Setting of Southern Mali. Am J Trop Med Hyg. 2022 Feb 28;106(4):1209-1214. doi: 10.4269/ajtmh.21-0788. PMID: 35226874; PMCID: PMC8991365.

Beshir KB, Diallo N, Somé FA, Sombie S, Zongo I, Fofana B, Traore A, Dama S, Bamadio A, Traore OB, Coulibaly SA, Maurice OS, Diarra A, Kaboré JM, Kodio A, Togo AH, Dara N, Coulibaly M, Dao F, Nikiema F, Compaore YD, Kabore NT, Barry N, Soulama I, Sagara I, Sirima SB, Ouédraogo JB, Djimde A, Sutherland CJ. Persistent Submicroscopic Plasmodium falciparum Parasitemia 72 Hours after Treatment with Artemether-Lumefantrine Predicts 42-Day Treatment Failure in Mali and Burkina Faso. Antimicrob Agents Chemother. 2021 Jul 16;65(8):e0087321. doi: 10.1128/AAC.00873-21. Epub 2021 Jul 16. PMID: 34060901; PMCID: PMC8284475.

Highlights of the Meeting

1. Research Progress

• Investigators from research sites in Burkina Faso, Gabon, Mali, and Niger presented updates on their work, particularly regarding recruitment for the ongoing KALUMA study.
• Preliminary results of the KALUMI study were shared at the African Society of Parasitology (SoAP) congress in a symposium format, hosted by the Gabonese Society of Parasitology-Mycology and Tropical Medicine (SOGAPAMME).

2. Site Reports

• CERMEL (Gabon): A total of 127 participants were recruited, with analyses revealing cases of reinfection from day 29 and mild to moderate side effects, including respiratory and gastrointestinal symptoms.
• GRAS (Burkina Faso): 160 patients were screened, but challenges arose due to the seasonality of malaria and inclusion criteria. Additional efforts were made to recruit younger participants.
• INSTech (Mali): 15 participants were randomized despite difficulties in sample collection and participant understanding of study requirements.
• AMU (Niger): A research center at the Faculty of Health Sciences in Niamey has been equipped for biomedical studies but faced delays due to the expiration of supplies.
• Bougoula Hameau (Mali): A total of 264 participants were recruited across multiple sites, with exclusions primarily due to vomiting and abnormalities in biological parameters.

3. Challenges and Solutions

• Recruiting young children was hindered by preventive campaigns.
• Logistical issues included sample transportation and staff turnover.
• Efforts to increase participant awareness about hospitalization protocols and sample collection were emphasized.

Outlook and Commitment

This congress provided a platform to share valuable lessons and identify innovative solutions to address the challenges encountered. The collective efforts of the WANECAM 2 consortium will continue to strengthen local capacities and advance the fight against malaria in Africa.

A Training Focused on Participants’ Expectations

At the outset, Professor Abdoulaye Djimdé conducted an interactive survey to better understand:

• The participants’ expectations for the training.
• The number of individuals who had already published a scientific article.
• The main challenges faced by those who had published.

These discussions helped tailor the content to meet the specific needs of the participants.

Clear and Ambitious Objectives

The main objective of the training was to help participants:

• Master scientific writing techniques.
• Identify funding and scholarship opportunities.
• Understand how to avoid plagiarism through transversal techniques.

These key topics were addressed through interactive presentations, allowing participants to become familiar with the various stages of scientific writing.

Experts Leading the Training

Several experts led this training, including:

• Professor Abdoulaye Djimdé, project coordinator, who shared his expertise on scientific writing.
• Dr. Mamadou Teketé, deputy of the ASSAP project (PI Mali), and Dr. Bakary Fofana, PI of the WANECAM 2 consortium, who presented strategies for successful publication.
• Moussa Djimdé, biostatistician, who provided in-depth insights into study design and statistical analysis.

A Closure Marked by Motivation and Recognition

The training ended on a positive note, with encouraging words from the trainers and the distribution of participation certificates. Participants now leave better equipped to face the challenges of scientific publication and contribute to the advancement of knowledge in their respective fields.