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

Association between number of previous malaria episodes and treatment failure among children and adults with laboratory-confirmed Plasmodium infection treated with pyronaridine-artesunate in Gabon: a retrospective cohort study. (PubMed, Malar J) - "Previous malaria episodes may constitute a surrogate marker for increased risk of recurrence and recrudescence, particularly in younger children. This association may reflect increased vulnerability or transient alterations in host immunity, although other unmeasured factors may also contribute. This understanding could improve malaria management in high-transmission settings, highlighting the need for targeted follow-up of patients at highest risk of treatment failure."

Journal • Retrospective data • Infectious Disease • Malaria

APP: A Clinical Study of Piperaquine, Pyronaridine, and Artesunate Administered in Combination in Healthy Adults (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: University of Oxford | Trial completion date: Aug 2027 ➔ Nov 2027 | Initiation date: Jun 2026 ➔ Nov 2026 | Trial primary completion date: Jun 2027 ➔ Nov 2027

Trial completion date • Trial initiation date • Trial primary completion date • Infectious Disease • Malaria

Evaluation of the effectiveness of artemether-lumefantrine and artesunate-pyronaridine each combined with single low-dose primaquine in adults with Plasmodium falciparum infection in Ethiopia: a phase 2/3, observer-masked, randomised, parallel-group trial. (PubMed, Lancet Microbe) - "Our findings reinforce the continued use of artemether-lumefantrine plus primaquine for treating uncomplicated P falciparum malaria. Pyronaridine-artesunate plus primaquine also shows promise as an alternative regimen. Continued surveillance remains essential to safeguarding both therapeutic effectiveness and diagnostic accuracy."

Journal • P2/3 data • Hematological Disorders • Infectious Disease • Malaria • Pain

Efficacy of chloroquine plus low-dose primaquine and pyronaridine-artesunate plus low-dose primaquine against Plasmodium vivax malaria in adults and transmission to mosquitoes in Ethiopia: a phase 2/3, observer-masked, randomised, parallel-group trial. (PubMed, Lancet Microbe) - "Both regimens treated P vivax malaria with high efficacy. Pyronaridine-artesunate plus low-dose primaquine rapidly interrupted transmission. The findings support further evaluation of pyronaridine-artesunate plus low-dose primaquine as a unified treatment strategy in co-endemic settings to improve malaria control and support malaria elimination efforts."

Journal • P2/3 data • Infectious Disease • Malaria • Pain

Molecular Surveillance of Plasmodium vivax and Plasmodium falciparum Drug Resistance Genes in the Republic of Korea: 2022-2025. (PubMed, Pathogens) - "In the Republic of Korea (ROK), chloroquine is the first-line treatment for Plasmodium vivax (P. vivax), and primaquine is also prescribed to prevent relapse...falciparum), atovaquone-proguanil, pyronaridine-artesunate, and mefloquine are recommended...Group comparisons revealed significant differences (p < 0.05), whereas temporal trends were not observed. Because drug resistance gene mutations can be closely linked to treatment, surveillance of drug resistance genes is expected to contribute to malaria eradication in the ROK through providing basic information related to treatment."

Journal • Infectious Disease • Malaria • ABCB1

Uncomplicated malaria as a risk factor for COVID-19 duration and severity in western Kenya and Burkina Faso (MALCOV): a prospective cohort study. (PubMed, Lancet Glob Health) - "This study shows that acute uncomplicated malaria co-infection does not adversely affect COVID-19 progression when appropriately treated. Moreover, serological evidence confirms that previous lifelong malaria exposure might provide some protection, with exposed individuals having faster symptom resolution."

Journal • Acute Respiratory Distress Syndrome • Gastroenterology • Hematological Disorders • Infectious Disease • Malaria • Novel Coronavirus Disease • Peptic Ulcer • Pulmonary Disease • Respiratory Diseases

APP: A Clinical Study of Piperaquine, Pyronaridine, and Artesunate Administered in Combination in Healthy Adults (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: University of Oxford

New P1 trial • Infectious Disease • Malaria

TADORE+: Tafenoquine and DHA-piperaquine (TADORE- Plus) (clinicaltrials.gov) - P4 | N=507 | Not yet recruiting | Sponsor: Menzies School of Health Research | N=280 ➔ 507 | Trial completion date: Dec 2027 ➔ Jun 2028 | Initiation date: Nov 2025 ➔ Jun 2026 | Trial primary completion date: Dec 2027 ➔ Jun 2028

Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date • Infectious Disease • Malaria

Effectiveness and safety of 7-day high-dose primaquine and single-dose tafenoquine versus 14-day low-dose primaquine in patients with Plasmodium vivax malaria (EFFORT): a multicentre, open-label, randomised, controlled, superiority trial. (PubMed, Lancet Infect Dis) - P3 | "Both unsupervised 7-day high-dose primaquine and single-dose tafenoquine were well tolerated in patients with normal G6PD activity and they had a lower risk of P vivax recurrence compared with those in the 14-day low-dose primaquine group, albeit with uncertain magnitude. Our findings support the effectiveness and operational feasibility of shorter radical cure regimens across diverse malaria-endemic settings."

Head-to-Head • Journal • CNS Disorders • Hematological Disorders • Infectious Disease • Malaria • Psychiatry • Schizophrenia

Artesunate-pyronaridine-atovaquone-proguanil and artesunate-fosmidomycin-clindamycin compared with standard artesunate-pyronaridine for the treatment of uncomplicated malaria (MultiMal): a randomised, controlled, clinical, phase 2 trial in Gabon and Ghana. (PubMed, Lancet Microbe) - "Antimalarial regimens of APAP and AFC have unique characteristics to tackle the development and spread of drug-resistant P falciparum malaria. Given that APAP and AFC were safe, well tolerated, and highly efficacious in this clinical phase 2 study, they constitute promising multidrug combination regimens for further clinical development."

Journal • P2 data • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Infectious Disease • Malaria • Peptic Ulcer

Health Systems Implementation and Molecular Surveillance of Multiple First-Line Treatments for Uncomplicated Malaria in Western Kenya (clinicaltrials.gov) - P=N/A | N=316 | Completed | Sponsor: Strathmore University

New trial • Infectious Disease • Malaria

Therapeutic efficacy of dihydroartemisinin-piperaquine and artesunate-pyronaridine combinations in the treatment of uncomplicated Plasmodium falciparum malaria in Ghana, 2023. (PubMed, Front Public Health) - "Currently, artesunate-amodiaquine (AS-AQ), artemetherlumefantrine (AL), and artesunate-pyronaridine (AP) are the first-line medicines for treating uncomplicated malaria whilst dihydroartemisinin-piperaquine (DHAP) is the second-line medicine. We conclude that the therapeutic efficacy level of DHAP has remained high (>90%) since the baseline study in 2020/2021. Also, the baseline efficacy level of AP is high (>90%) warranting the use of both DHAP and AP in the treatment of uncomplicated malaria in the country."

Journal • Hematological Disorders • Infectious Disease • Malaria

Artemether-lumefantrine versus pyronaridine-artesunate for the treatment of malaria in patients with mild to moderate COVID-19 in Kenya and Burkina Faso: a randomised open-label trial (MALCOV). (PubMed, EClinicalMedicine) - P3 | "Several antimalarials exhibit antiviral activity against SARS-CoV-2 in vitro and have been suggested as potential therapeutic candidates for COVID-19, particularly pyronaridine-artesunate (PA), despite disappointing clinical results with chloroquine and hydroxychloroquine. Both treatments were highly effective as antimalarials and should continue to be considered first- or second-line treatment options for uncomplicated malaria in patients with mild to moderate COVID-19. Gates Foundation."

Journal • Infectious Disease • Malaria • Novel Coronavirus Disease • Respiratory Diseases

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