Efficacy and safety of fosmidomycin-piperaquine as non-artemisinin-based combination therapy for uncomplicated falciparum malaria - A single-arm, age-de-escalation proof of concept study in Gabon

26 Dec 2017

Ghyslain Mombo-Ngoma, Jonathan Remppis, Moritz Sievers, Rella Zoleko Manego, Lilian Endamne, Lumeka Kabwende, Luzia Veletzky, The Trong Nguyen, Mirjam Groger, Felix Lötsch,  Johannes Mischlinger, Lena Flohr, Johanna Kim, Chiara Cattaneo, David Hutchinson,  Stephan Duparc, Joerg Moehrle, Thirumalaisamy P. Velavan, Bertrand Lell, Michael Ramharter, Ayola Akim Adegnika, Benjamin Mordmüller, and Peter G. Kremsner

Clinical Infectious Diseases

doi: 10.1093/cid/cix1122



Fosmidomycin-piperaquine is being developed as non-artemisinin-based combination therapy to meet the challenge of emerging artemisinin resistance.


The study was a phase 2 single arm open label proof of concept study of the efficacy, tolerability and safety of fosmidomycin-piperaquine for the treatment of uncomplicated Plasmodium falciparum mono-infection in Gabon. Adults and children of both sexes with initial parasite counts between 1,000 and 150,000/µL were eligible for oral treatment with fosmidomycin (twice daily doses of 30mg/kg), and piperaquine (once daily dose of 16mg/kg) for three days and followed-up for 63 days. The primary efficacy endpoint was the per protocol PCR-corrected Day 28 adequate clinical and parasitological response (ACPR).


100 patients were enrolled. The PCR-corrected Day 28 ACPR rate was 83/83 or 100% (95% CI: 96-100). Fourteen patients had asexual parasitaemia between Day 28 and Day 63; all were typed by PCR as new infections. Fosmidomycin-piperaquine therapy led to rapid parasite clearance (median: 36h; IQR: 6-60) and fever clearance time (median: 12h; IQR: 6-48). The electrocardiogram assessments showed two subjects with QT corrected from the formula of Bazett (QTcB) >500msec following study drug administration. The majority of adverse events affected the gastrointestinal and respiratory tracts and were transient and mild to moderate in severity.


This is the first report of the use of the combination fosmidomycin-piperaquine, a non-artemisinin-based combination therapy in clinical development. The combination appeared to have high efficacy, to be safe and well tolerated despite observed transient changes in electrocardiogram with prolongation of the QT interval.

Read the full article on Oxford Academic's website.