Synthetic antimalarial effective, safe against P. falciparum
Treatment using a synthetic alternative to artemisinins appeared comparable to artemether-lumefantrine against Plasmodium falciparum malaria in adolescent and adult patients, according to the results of a phase 3 trial published in Clinical Infectious Diseases.
Results showed that treatment with a combination of arterolane maleate (AM) — a new synthetic trioxolane — and piperaquine phosphate (PQP) was equally effective and safe compared with artemether-lumefantrine (A-L). The AM-PQP combination also had other favorable factors, according to researchers.
“The advantages of AM–PQP are once-daily dosing and low pill burden as well as a long duration of posttreatment prophylaxis,” they wrote. “Availability of this synthetic, rapid-acting medicine would have beneficial impact on patient access, treatment, and adherence.”
Artemisinin combination therapies (ACTs) are recommended by WHO as a first-line treatment for uncomplicated P. falciparum malaria in endemic regions, the researchers noted. However, as a derivative of the sweet wormwood plant, artemisinin is subject to supply interruptions because of climate change.
To identify a new synthetic antimalarial, a fixed dose of AM (150 mg), as an alternative to artemisinins, and PQP (750 mg) was compared with A-L (20 mg-120 mg) in patients with uncomplicated P. falciparum malaria in nine countries in Asia and Africa.
In the randomized, multicenter, comparative, double blind, noninferiority trial, patients aged 12 to 65 years were randomly assigned in a 2:1 ratio either AM-PQP or A-L.
Of the 1,072 patients enrolled in the study, 939 completed treatments — 638 in the group that received AM-PQP and 301 who were given A-L. Researchers observed comparable cure rates at day 28 and safety of treatment in the two groups.
The PCR-corrected adequate clinical and parasitological response (PCR–corrected ACPR) on day 28 in the intent-to-treat population was 92.86% for AM-PQP and 92.46% for A-L; it was 99.25% for AM-PQP and 99.07% for A-L in the per-protocol population. The overall incidence of treatment-emergent adverse effects was comparable as well, with headache, abdominal pain, cough, vomiting, nausea and diarrhea observed most frequently, the researchers said. Serious adverse events — abdominal pain, spontaneous abortion, sepsis, suspected meningeal syndrome — were seen in four patients in each group, they reported.
“AM–PQP showed comparable efficacy and safety to A–L in the treatment of uncomplicated P. falciparum malaria in adolescent and adult patients,” the researchers concluded. “AM–PQP demonstrated high clinical and parasitological response rates as well as rapid parasite clearance.” – by Gerard Gallagher
Disclosure: Please see the full study for a list of all authors’ relevant financial disclosures.