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Peer-reviewedCC BYAntimicrobial Agents and Chemotherapy

Modeling the potential effect of cabamiquine-pyronaridine for chemoprevention against Plasmodium falciparum malaria

  • Lucy C. Okell1
  • Perrine Courlet2
  • Filippo Venezia3
  • Claude Oeuvray4
  • Claudia Demarta4
  • Thomas Spangenberg4
  • Joseph Okebe4
4 affiliations
  1. 1MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, United Kingdom
  2. 2Merck Institute for Pharmacometrics, Ares Trading S.A. (an affiliate of Merck KGaA, Darmstadt, Germany), Lausanne, Switzerland
  3. 3The Healthcare Business of Merck KGaA, Darmstadt, Germany
  4. 4Global Health R&D of Merck Healthcare, Ares Trading S.A. (an affiliate of Merck KGaA, Darmstadt, Germany), Eysins, Switzerland
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Abstract

Preventive treatment (chemoprevention) is a key intervention for reducing the burden of Plasmodium falciparum malaria in children. The impact of the current widely used drug combination, sulfadoxine-pyrimethamine-amodiaquine (SP-AQ), is challenged by emerging drug resistance and adherence to multi-day dosing. Cabamiquine is a novel antimalarial with activity against liver- and blood-stage malaria parasites, administered as a single dose, and under development in combination with pyronaridine. We used mathematical modeling to translate early phase 1 clinical results into estimates of its potential impact as malaria chemoprevention. Pharmacokinetic-pharmacodynamic (PKPD) models of cabamiquine and pyronaridine were combined, assuming Bliss independence, to estimate time-varying protection against infection. PKPD results were incorporated into an established individual-based malaria transmission model to estimate the impact of seasonal malaria chemoprevention (SMC) across settings with differing transmission and seasonality. Cabamiquine-pyronaridine was predicted to provide protection of >95% for approximately 4 weeks, slightly outperforming SP-AQ even in children who fully adhere to SP-AQ treatment. Six weeks after treatment, cabamiquine-pyronaridine protection dropped for the regimens containing <200 mg cabamiquine, but the combination could still outperform SP-AQ at doses ≥200 mg. If deployed as SMC, a longer duration of protection may enable fewer, more widely spaced treatment cycles while maintaining impact, improving projected cost-effectiveness. Cabamiquine-pyronaridine shows strong potential as a next-generation single-dose chemoprevention regimen, supporting continued clinical development and evaluation.

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Cite

BibTeXRIS
BibTeX
@article{okell2026modeling,
  title = {{Modeling the potential effect of cabamiquine-pyronaridine for chemoprevention against Plasmodium falciparum malaria}},
  author = {Lucy C. Okell and Perrine Courlet and Filippo Venezia and Claude Oeuvray and Claudia Demarta and Thomas Spangenberg and Joseph Okebe},
  journal = {Antimicrobial Agents and Chemotherapy},
  year = {2026},
  month = nov,
  doi = {10.1128/aac.00434-26},
  url = {https://doi.org/10.1128/aac.00434-26},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Modeling the potential effect of cabamiquine-pyronaridine for chemoprevention against Plasmodium falciparum malaria
AU  - Lucy C. Okell
AU  - Perrine Courlet
AU  - Filippo Venezia
AU  - Claude Oeuvray
AU  - Claudia Demarta
AU  - Thomas Spangenberg
AU  - Joseph Okebe
PY  - 2026
DA  - 2026/11/04
JO  - Antimicrobial Agents and Chemotherapy
DO  - 10.1128/aac.00434-26
UR  - https://doi.org/10.1128/aac.00434-26
AB  - Preventive treatment (chemoprevention) is a key intervention for reducing the burden of Plasmodium falciparum malaria in children. The impact of the current widely used drug combination, sulfadoxine-pyrimethamine-amodiaquine (SP-AQ), is challenged by emerging drug resistance and adherence to multi-day dosing. Cabamiquine is a novel antimalarial with activity against liver- and blood-stage malaria parasites, administered as a single dose, and under development in combination with pyronaridine. We used mathematical modeling to translate early phase 1 clinical results into estimates of its potential impact as malaria chemoprevention. Pharmacokinetic-pharmacodynamic (PKPD) models of cabamiquine and pyronaridine were combined, assuming Bliss independence, to estimate time-varying protection against infection. PKPD results were incorporated into an established individual-based malaria transmission model to estimate the impact of seasonal malaria chemoprevention (SMC) across settings with differing transmission and seasonality. Cabamiquine-pyronaridine was predicted to provide protection of >95% for approximately 4 weeks, slightly outperforming SP-AQ even in children who fully adhere to SP-AQ treatment. Six weeks after treatment, cabamiquine-pyronaridine protection dropped for the regimens containing <200 mg cabamiquine, but the combination could still outperform SP-AQ at doses ≥200 mg. If deployed as SMC, a longer duration of protection may enable fewer, more widely spaced treatment cycles while maintaining impact, improving projected cost-effectiveness. Cabamiquine-pyronaridine shows strong potential as a next-generation single-dose chemoprevention regimen, supporting continued clinical development and evaluation.
SN  - 1098-6596
SN  - 0066-4804
ER  -