The  early  preclinical and clinical development of ganaplacide (KAF156), a novel antimalarial compound

ABSTRACT

Introduction: Ganaplacide (previously known as KAF156) is a novel antimalarial compound part of the imidazolopiperazine family.

Areas covered: At the time of writing, a total of eight studies addressing its preclinical and clinical development have been published on this compound, which is currently in phase 2 of clinical development, alongside lumefantrine in a novel soluble formulation as combination partner. This review provides an overview and interpretation of the published pre-clinical and clinical data of this possible next-generation antimalarial drug.

Expert opinion: In the search for a ‘magic bullet’ in malaria therapy and prophylaxis facilitating single encounter radical cure and prophylaxis, ganaplacide demonstrates some promising properties toward this ultimate goal. The available data suggest that ganaplacide exerts multi-stage antimalarial activity, and that its pharmacokinetic profile potentially allows for a simplified dosing regimen compared to that of existing antimalarial drug combinations. The first in-patient results demonstrate promising single-dose antimalarial activity, and no serious in-human safety and tolerability concerns have been reported to date.

KEYWORDS:

• Antimalarial
• clinical development
• ganaplacide
• imidazolopiperazine
• KAF156
• malaria
• Single Encounter Radical Cure and Prophylaxis (SERCaP)

Article highlights box

• Ganaplacide is the first imidazolopiperazine class representative currently undergoing phase 2 clinical trials to evaluate its potential as antimalarial combination partner and to establish the most appropriate dosing regimen

• Lumefantrine in soluble dispersion formulation (LSDF) appears to be the most promising partner compound at this stage

• Ganaplacide is active against all stages of P. falciparum

• The mechanism of action of KAF156 remains to be elucidated

Resistance-conferring polymorphisms in the pfcarl, pfact and pfugt genes are inducible in vitro

Acknowledgments

We thank David Hughes and Cornelis Winnips, Novartis, for critical appraisal of the manuscript.

Declaration of Interests

MP Grobusch is International Lead Principal Investigator on the ongoing ganaplacide phase 2 trial [19]. GM Mombo-Ngoma is CERMEL/Gabon site Principal Investigator, and R Koller served as coinvestigator on that trial. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.