Pyramax (artesunate/pyronaridine) / Medicines for Malaria Venture, Shin Poong Pharma - LARVOL DELTA

Efficacy of artemether-lumefantrine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso, 2020-2021. (PubMed, Malar J) - "Continued low uncorrected efficacy of AL was observed in all sites, with one half to one third of children returning to the clinic with repeat infection within 28 days. PCR-corrected efficacy was at or below 90% for AL. AS-PYR and DP were associated with low rates of recurrent parasitaemia suggesting a potential for implementing a multiple first-line therapy approach with non-AL ACT. This approach will allow to preserve future use of lumefantrine and improve patient outcomes."

Journal • Infectious Disease • Malaria

Spatio-temporal trends of artemisinin-based combination therapy efficacy from 2010 to 2024 in sub-Saharan Africa: a systematic review and meta-analysis. (PubMed, BMC Infect Dis) - "While AS-AQ, DHA-PPQ, and AS-PY have maintained high efficacy over time in sub-Saharan Africa, there is a concern about the declining efficacy of AL in some West and East African countries. Our findings suggest that AS-PY could be a promising candidate for inclusion in first-line malaria treatments to address the declining efficacy of AL. Continuous monitoring of ACT efficacy, innovative and efficient control strategies are crucial to prevent the spread of antimalarial drug resistance."

Journal • Retrospective data • Review • Infectious Disease • Malaria

WITHDRAWN Treatment of partial artemisinin-resistant Plasmodium falciparum malaria with pyronaridine-artesunate (Pyramax®) in Gia Lai province Vietnam (ASTMH 2025) - "Patients received Pyramax® once daily for 3 days, dosed according to body weight, plus single-dose primaquine (0.25 mg/kg) on Day 0. The eight patients who experienced a recrudescence of infection had lower (P=0.065) blood pyronaridine concentrations (median 33.3 ng/mL, range: 12.4 to 90.5) compared to the 95 patients who were malaria-free by Day 42 (median 47.6 ng/mL, range: 10.6 to 123.0). Although Pyramax® remains efficacious in treating P. falciparum the lower pyronaridine concentrations in those patients who recrudesced is of concern with reduced exposure of the long acting pyronaridine."

Infectious Disease • Malaria

SAFIRE: Safety of Antimalarials in the FIRst trimEster (clinicaltrials.gov) - P3 | N=1510 | Recruiting | Sponsor: Liverpool School of Tropical Medicine | Not yet recruiting ➔ Recruiting | Initiation date: Jul 2025 ➔ Sep 2025

Enrollment open • Head-to-Head • Trial initiation date • Infectious Disease • Malaria

Investigating the resurgence of malaria in Rwanda: factors contributing to rising cases amidst near-eradication success and strategies for sustained control. (PubMed, Ann Med Surg (Lond)) - "The 2025 Rwanda Malaria Strategic Plan highlights new drugs (dihydroartemisinin-piperaquine and artesunate-pyronaridine), regional cooperation, and partially subsidized insecticide-treated nets for at-risk populations. Gaps are Plasmodium vivax strategies, availability of funds, and evaluation of behavioral interventions. Elimination of lymphatic filariasis in Rwanda depends on multi-sectoral approaches that work to alleviate environmental, socioeconomic, and operational problems, cut down on recrudescence, and maintain sustained progress."

Journal • Review • Infectious Disease • Malaria

Efficacy, safety and tolerability of a single dose sulfadoxine-pyrimethamine plus artesunate-pyronaridine (SPAP) for the treatment of uncomplicated malaria in adults and children in Gabon: the 1-D-CURE study - a pragmatic randomized controlled . (ASTMH 2025) - "Positive patients with a signed informed consent and eligible are randomized in a 1:1 ratio to either the intervention group receiving a single dose SPAP or artemether-lumefantrine (AL). The findings suggest that single dose SPAP is non-inferior to standard 3-day AL based on cure rates, using a 5% absolute margin. The single day multidrug combination therapy is well tolerated and safe."

Clinical • Late-breaking abstract • Infectious Disease • Malaria

Understanding Drug Sources in Early Pregnancy: Insights from a Pregnancy Exposure Registry in Burkina Faso (ASTMH 2025) - "A total of 951 medications were identified in the first trimester, with quinine accounting for 32.4%, followed by paracetamol (11.9%), phloroglucinol (8.9%), artemether-lumefantrine (9.0%), and pyronaridine-artesunate (6.1%). Relying solely on health facility records misses nearly half of early pregnancy drug exposures. These findings underscore the importance of utilising multi-source data to enhance pharmacovigilance systems and ensure the accurate monitoring of medication use during pregnancy, particularly in resource-limited settings."

Infectious Disease

Natural in vitro susceptibility of Plasmodium falciparum to pyronaridine over 2009-2023 in French Guiana (ASTMH 2025) - "Currently, only artemether-lumefantrine remains effective in the region...Correlation between pyronaridine and other aminoquinoline derivatives including chloroquine, monodesethylamodiaquine, and mefloquine was assessed (r2=0.01; r2=0.04; r2=0.11, respectively), but no cross-resistance was found...However, the synonymous mutation PfMDR1S1034S, observed in 63% of French Guiana isolates, was associated with decreased pyronaridine susceptibility (p < 0.0001). The findings of this study suggest that artesunate-pyronaridine could be a new treatment alternative for P. falciparum in the Amazon region."

Preclinical • Infectious Disease • Malaria • ABCB1

Finally - evidence-based regimens for single, low dose primaquine for transmission blocking. How did we do it? (ASTMH 2025) - "The ACTs were dihydroartemisinin piperaquine, artesunate pyronaridine, artesunate amodiaquine (ASAQ), artesunate mefloquine, artemether lumefantrine (AL), and the triple ALAQ. These regimens offer flexibility for malaria control programmes and guidance for drug manufacturers wishing to coblister SLDPQ with ACTs. The WHO should reinstate the 3.75 mg for prequalification and determine which of these regimens should be incorporated into their treatment guidelines to advance malaria elimination."

Infectious Disease • Malaria

Tackling Drug Resistance in Malaria Treatment in Rwanda: Advancing Multiple First-Line Therapies as a Strategic Response (ASTMH 2025) - "In response, Rwanda launched a 2024 strategy deploying three ACTs—Artemether-Lumefantrine (AL), Dihydro-Artemisinin-Piperaquine (DHP), and Pyronaridine-Artesunate (ASPY)—in a multi-first line treatment (MFT) approach. Novel strategies like triple ACTs or sequential therapies offer additional potential to curb resistance.Urgent implementation of MFT policies alongside cross-border surveillance is essential to address resistance effectively. Such measures not only reduce treatment failures but also ensure the continued efficacy of malaria therapies, protecting public health in affected regions."

Clinical • Infectious Disease • Malaria

Pyronaridine-artesunate for treating uncomplicated Plasmodium falciparum malaria. (PubMed, Cochrane Database Syst Rev) - "Pyronaridine-artesunate was efficacious against uncomplicated P falciparum malaria; achieved a PCR-adjusted treatment failure rate of less than 8% at days 28 and 42; and may be at least as good as artesunate-amodiaquine and artesunate-mefloquine (based on 1 RCT per drug) and may be at least as good as, or better than, artemether-lumefantrine. Pyronaridine-artesunate increases the risk of episodes of abnormally raised ALT and AST compared to other studied therapeutics."

Clinical • Journal • Review • Hepatology • Infectious Disease • Liver Failure • Malaria

Health system challenges and facilitators associated with adaptive cycling deployment of multiple first-line treatment for uncomplicated malaria: a pilot study in a malaria-endemic region of Kenya. (PubMed, Malar J) - "Adaptive cycling MFT implementation is feasible in Kenya with adequate planning and addressing health systems challenges. Stakeholder engagement and continuous training were critical for success. Policy implications and regional cooperation potential warrant exploration in other sub-Saharan African countries with different deployment contexts."

Journal • Infectious Disease • Malaria

Strategies for mitigating emerging artemisinin-based antimalarial drug resistance in Rwanda: a promising approach for managing therapies in malaria-endemic countries. (PubMed, BMJ Glob Health) - "Malaria treatment failures associated with reduced efficacy of chloroquine (CQ) and amodiaquine (AQ) antimalarial drugs emerged in Rwanda during the 1980s, prompting the policy shift towards adopting artemisinin-based combination therapies in 2006 as an alternative...Particularly, artemether-lumefantrine (AL) efficacy has significantly decreased, probably due to the emergence of Plasmodium falciparum (Pf) genomic mutations...A significant rise in Pfkelch13 mutations, particularly A675V associated with AL resistance, was mainly reported in the western region; therefore, artesunate-pyronaridine was recommended...On the contrary, AL was maintained in the southern region, where the prevalence of the R561H mutation was low. Insights from this data-driven model will inform its extension to other malaria-endemic countries facing emerging Pf genetic diversity."

Journal • Review • Infectious Disease • Malaria

Making the most of existing antimalarial medicines: a single dose cure with sulfadoxine-pyrimethamine plus artesunate-pyronaridine. (PubMed, Malar J) - "Multi-drug regimens, such as artemether-lumefantrine-amodiaquine appear to be well tolerated, but these are under development to address emerging resistance to lumefantrine and will be unlikely to improve compliance...Mefloquine is excluded for tolerability concerns, amodiaquine because of its use in seasonal malaria chemoprevention, and lumefantrine and piperaquine due to concerns of emerging resistance...Importantly, a comprehensive clinical evaluation will generate valuable real-world insights into community acceptance and operational feasibility. This information will be an important foundation for future design of single dose malaria therapies involving new chemical entities."

Journal • Review • Infectious Disease • Malaria

Evaluation of in vitro drug-drug interactions of ivermectin and antimalarial compounds. (PubMed, Malar J) - "Several of the commonly used antimalarial drugs, are mostly or in part metabolized by CYP3A4 and showed a notable DDI effect on the in vitro metabolism of ivermectin. This could potentially lead to clinically important pharmacokinetic and pharmacodynamic DDIs if co-administered, and needs to be evaluated in prospective clinical trials."

Journal • Preclinical • Infectious Disease • Malaria • CYP3A4

Efficacy of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine and artesunate-pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria in Mozambique, 2022. (PubMed, Malar J) - P4 | "AL and AS-AQ remain effective, as their efficacy remained above the 90% WHO-recommended cut-off. DP and AS-PY also showed therapeutic efficacy above the WHO-acceptable cut-off and could be used as first-line treatments when needed. All four artemisinin-based combinations were well tolerated, with minimal safety concerns."

Journal • Infectious Disease • Malaria

The transmission blocking activity of artemisinin-combination, non-artemisinin, and 8-aminoquinoline antimalarial therapies: A pooled analysis of individual participant data. (PubMed, PLoS Med) - "We found marked differences among ACTs and single low-dose 8-aminoquinoline drugs in their ability and speed to block transmission. The findings from this analysis can support treatment policy decisions for malaria elimination and be integrated into mathematical models to improve the accuracy of predictions regarding community transmission and the spread of drug resistance under varying treatment guidelines."

Journal • Retrospective data • Infectious Disease • Malaria

Therapeutic efficacy monitoring of pyronaridine-artesunate (Pyramax®) in treating uncomplicated Plasmodium falciparum malaria in Gia Lai province, Vietnam from 2022 to 2023. (PubMed, J Antimicrob Chemother) - "Although Pyramax® remains efficacious in treating P. falciparum, the lower pyronaridine concentrations in patients who had recrudescent malaria are worrisome and suggest that reduced pyronaridine exposure may be responsible for the Pyramax® treatment failures."

Journal • Infectious Disease • Malaria

Efficacies of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria in children aged 6 months to 10 years in Uganda: a randomised, open-label, phase 4 clinical trial. (PubMed, Lancet Infect Dis) - "Artemether-lumefantrine was associated with a higher risk of recurrent malaria than other antimalarial combinations tested, and K13 mutations were associated with delayed parasite clearance. Changes in first-line therapy for uncomplicated malaria must be considered in response to suboptimal efficacy of artemether-lumefantrine."

Journal • P4 data • Hematological Disorders • Infectious Disease • Malaria • Respiratory Diseases

Fractional curative killing of pyronaridine or artesunate combinations with tafenoquine, 4-aminoquinolines, or azithromycin in a murine malaria-luciferase model. (PubMed, Antimicrob Agents Chemother) - "In the pharmacodynamic high parasitemia Plasmodium berghei ANKA-luciferase mouse blood-stage model, we investigated curative interaction analysis of multiple, daily dosed, short half-life, artesunate or single-dose, long half-life, pyronaridine against three single-dose, long half-life, quinolines-chloroquine, amodiaquine, and tafenoquine. Short blood half-life azithromycin, requiring multiple daily doses, was additive to artesunate or pyronaridine in fractional curative dose combination killing. Murine malaria high parasitemia drug interactions at the curative metric in vivo are a potential benchmark for human studies."

Journal • Preclinical • Infectious Disease • Malaria

Single low dose primaquine to block the transmission of Plasmodium falciparum-proposed stand-alone and ACT-adapted regimens. (PubMed, BMC Med) - "These regimens offer flexibility for malaria control programmes and guidance for drug manufacturers wishing to co-blister SLDPQ with ACTs. The WHO should reinstate the 3.75 mg tablet for prequalification and determine which regimens should be incorporated into their treatment guidelines to advance malaria elimination."

Journal • Hematological Disorders • Infectious Disease • Malaria • Metabolic Disorders

SAFIRE: Safety of Antimalarials in the FIRst trimEster (clinicaltrials.gov) - P3 | N=1510 | Not yet recruiting | Sponsor: Liverpool School of Tropical Medicine

Head-to-Head • New P3 trial • Infectious Disease • Malaria

Preferential transmission of minority and drug-resistant clones in polyclonal infections in Mali. (PubMed, Malar J) - "Overall, these findings indicate that parasite dynamics and clonal transmissibility are highly complex, even after ACT. This complexity may have important epidemiological implications, as it suggests the transmission of minority clones and highlights the impact of drug resistance markers on transmissibility."

Journal • Infectious Disease • Malaria

SY148 - Echinococcosis: neglected but expanding (ESCMID Global 2025) - "The first talk will highlight the rising incidence and importance of the condition in Europe. In the second talk, the management of both alveolar and cystic echinococcosis will be discussed, with focus on new imaging techniques (PET-CT) and repurposing of drugs (e.g. artesunate/pyronaridine)."

Infectious Disease

Congenital malaria in newborns of mothers living in highly endemic parts of Kinshasa, Democratic Republic of Congo. (PubMed, Paediatr Int Child Health) - "Although 10 of 72 women (16.7%) with placental malaria gave birth to low-weight infants, the association was not statistically significant. Although this first assessment of congenital malaria by PCR in DRC found a low prevalence, maternal and placental malaria at delivery were still associated with congenital malaria, highlighting the importance of maternal health in preventing neonatal infections.Abbreviations: Aor adjusted odds ratio; CI confidence interval; cOR crude odds ratio; DNA de-oxyribonucleic acid; GAPDH glyceraldehyde-3-posphate dehydrogenase; g/dL grams per decilitre; Hb haemoglobin; IQR interquartile range; IPTp-SP Intermittent Preventive Treatment in pregnancy with sulfadoxine-pyrimethamine; ITN insecticide-treated nets; PA pyronaridine-artesunate; PCR polymerase chain reaction; RDT rapid diagnostic tests; SD; standard deviation; uRDTs ultra-sensitive rapid diagnostic tests; WHO World Health Organization; µL microlitre."

Journal • Infectious Disease • Malaria • GAPDH