Scoping Review of Antimalarial Drug Candidates in Phase I and II Drug Development

Azrin N. Abd-Rahman, Sophie Zaloumis, James S. McCarthy, Julie A. Simpson, Robert J. Commons

Research output: Contribution to journalReview articlepeer-review

16 Citations (Scopus)
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Abstract

The emergence and spread of parasite resistance to currently available antimalarials has highlighted the importance of developing novel antimalarials. This scoping review provides an overview of antimalarial drug candidates undergoing phase I and II studies between 1 January 2016 and 28 April 2021. PubMed, Web of Science, Embase, clinical trial registries, and reference lists were searched for relevant studies. Information regarding antimalarial compound details, clinical trial characteristics, study population, and drug pharmacokinetics and pharmacodynamics (PK-PD) were extracted. A total of 50 studies were included, of which 24 had published their results and 26 were unpublished. New antimalarial compounds were evaluated as monotherapy (28 studies, 14 drug candidates) and combination therapy (9 studies, 10 candidates). Fourteen active compounds were identified in the current antimalarial drug development pipeline together with 11 compounds that are inactive, 6 due to insufficient efficacy. PK-PD data were available from 24 studies published as open-access articles. Four unpublished studies have made their results publicly available on clinical trial registries. The terminal elimination half-life of new antimalarial compounds ranged from 14.7 to 483 h. The log10 parasite reduction ratio over 48 h and parasite clearance half-life for Plasmodium falciparum following a single-dose monotherapy were 1.55 to 4.1 and 3.4 to 9.4 h, respectively. The antimalarial drug development landscape has seen a number of novel compounds, with promising PK-PD properties, evaluated in phase I and II studies over the past 5 years. Timely public disclosure of PK-PD data is crucial for informative decision-making and drug development strategy.

Original languageEnglish
Article numbere01659-21
Pages (from-to)1-18
Number of pages18
JournalAntimicrobial Agents and Chemotherapy
Volume66
Issue number2
DOIs
Publication statusPublished - Feb 2022

Bibliographical note

Funding Information:
This work is supported in part by the Australian Centre for Research Excellence in Malaria Elimination, funded by the Australian National Health and Medical Research Council of Australia (NHMRC; 1134989). J.A.S. is funded by an Australian NHMRC Leadership Investigator Grant (1196068). J.S.M. is funded by an NHMRC Program Grant (1132975) and Practitioner Fellowship (1041802). R.J.C. is supported by an Australian NHMRC Emerging Leader Investigator Grant (1194702). The review was done completely independent from any funding bodies.

Publisher Copyright:
© 2022 Abd-Rahman et al.

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