Discussion
acoziborole, anxiety
ADVERSE EVENTS, EVENTS, DISEASE, COMPLICATIONS
In this open-label, non-comparative study, a single 960 mg oral dose of acoziborole in fasted conditions showed an efficacy of 95·2% reached in 159 of 167 patients with late-stage gambiense HAT, corresponding to results from studies with NECT (94%).The criteria for success used in previous NECT studies were less stringent and consequently less favourable towards acoziborole. In addition to these differences, acoziborole is less cumbersome than previous treatments, which is an important advantage because the drug requires a single oral administration in fasted conditions compared with 10 days of oral fexinidazole administered with food or NECT administered in hospital (twice per day infusions of eflornithine for 7 days plus 10 days of three times per day of oral nifurtimox). The logistics (ie, shipment and drug storage) are simplified as acoziborole is packaged in a small box whereas NECT is packaged in a 4 kg box. Patient management is easier, unlike with NECT, because administration of acoziborole does not require hospital admission, highly skilled health personnel, or a lumbar puncture.The principal limitation of this study was the absence of a comparator or control group, precluding randomisation; instead comparisons were made with historical data, as permitted by WHO.The proportion of treatment-emergent adverse events related to treatment was low and all events were mild or moderate in intensity. No substantial drug-related safety signals were identified in this study. All 38 drug-related treatment-emergent adverse events occurred on days 1–5, mainly on day 1. Serious events were reported more often in patients with late-stage gambiense HAT and mainly occurred after patients were discharged from hospital; none were considered treatment related. The safety profile of acoziborole compares favourably with those of NECT and pentamidine.Pharmacokinetic analysis was performed on dry blood spots and CSF sampling, and supported the results observed in healthy volunteers in a phase 1 study (unpublished). The long half-life (around 14 days) and exposure observed in blood and CSF mean that concentrations of the active drug remain higher than the antiparasitic efficacy (ECBased on these findings, the benefit–risk profile of acoziborole for adults and adolescents with gambiense HAT, regardless of disease stage, is considered positive. Given the high efficacy and good safety at all stages of disease, acoziborole eliminates the need for routine lumbar puncture at diagnosis and during follow-up, which requires trained staff, is associated with complications, and is a source of anxiety for patients. These advantages and the fact that a single oral dose would be more accessible to patients living in remote areas without easy access to health care, means that acoziborole holds promise in the efforts to reach the WHO goal of interrupting HAT transmission by 2030. To facilitate the use of acoziborole in treatment of suspected patients with negative parasitological assays for gambiense HAT, the integration of new tools into the national and global policies part of WHO HAT elimination Technical Advisory Group has recommended extending the safety database to detect uncommon adverse events. A double-blind safety study investigating the use of acoziborole versus placebo in this at-risk population is ongoing in the Democratic Republic of the Congo and Guinea (

