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A single dose of oral acoziborole proved to be efficacious and safe for adults and adolescents with gambiense human African trypanosomiasis (HAT), also known as "sleeping sickness," suggesting its promise in interrupting transmission, a single-arm phase II/III trial showed.

Over 18 months of follow-up, the treatment success rate was 95.2% in those with late-stage disease and 98.1% in the evaluable population, reported Antoine Tarral, MD, of the Drugs for Neglected Diseases initiative in Geneva, Switzerland, and colleagues.

All 41 patients with early- or intermediate-stage disease and 96% of those with late-stage disease completed the last 18-month follow-up visit, and while four deaths occurred during the study, none were considered related to treatment, they noted in .

Acoziborole is "effective across every stage of the disease, thereby eliminating the many barriers currently in place for people most vulnerable to the disease," said Tarral in a press release. Previous treatment options required lengthy travel and hospitalization, but this oral one-dose treatment opens the door to "screen-and-treat approaches at the village level."

"Given the high efficacy and favorable safety profile, acoziborole holds promise in the efforts to reach the WHO goal of interrupting HAT transmission by 2030," Tarral and team concluded.

Gambiense HAT is caused by the microscopic parasite Trypanosoma brucei gambiense and is transmitted by the tsetse fly found in sub-Saharan Africa. The parasites enter the blood and lymphatic system, and attack the central nervous system (CNS). It can eventually be fatal if not treated, which is not uncommon given that many people who are at risk for the disease live in remote rural areas where health services are lacking.

Other treatment options include intramuscular pentamidine injections, or an intravenous drip of nifurtimox-eflornithine combination therapy for 7 days, which requires hospitalization. A 10-day treatment with fexinidazole was another option for late-stage disease, but this required a spinal tap to assess disease severity before it could be offered to patients.

Of note, gambiense HAT has been on the decline over the last decade or so. In 2020, the fewer than 700 cases, down from more than 10,000 a year before 2009.

In an , Jacques Pépin, MD, MSc, of the University of Sherbrooke in Canada, noted that acoziborole combines "all the desired qualities of a trypanocidal drug: well absorbed orally, long half-life, good penetration into the CNS, and few serious adverse effects."

"Gambiense HAT could become the first disease that is eradicated thanks to a drug rather than a vaccine," he added.

Pépin pointed out that development of this drug is not profitable, as there are too few people that need it. "The pharmaceutical industry had no financial motivation to seek new products for a disease with a market representing a few tens of thousands of cases per year, living in rural and impoverished regions of sub-Saharan Africa," he wrote, explaining that the study was carried out as a result of efforts and funding from several nonprofit organizations.

Although the trial was small and not randomized, nor did it have a control group, it was well carried out, he said, considering the recent drastic reduction in patients with the disease, and the distances between them.

The next step -- "already underway" -- will be to test the drug in 900 patients that are serologically positive and asymptomatic (the only way the disease can be eradicated is to also treat asymptomatic people), he said.

For the current study, Tarral and colleagues enrolled 208 patients ages 15 and up -- 41 with early- or intermediate-stage disease and 167 with late-stage disease -- who were recruited from 10 Democratic Republic of the Condo and Guinea hospitals from October 2016 to March 2019. Mean age was 34, and 56% were men. The primary outcome was treatment success at 18 months, defined as cure or probable cure (absence of trypanosomes and <20 white blood cells/μL of cerebrospinal fluid).

Oral acoziborole was administered as a single 960-mg dose to patients on an empty stomach.

Overall, there were 600 treatment-emergent adverse events among 75% of patients. Of these, 93% were mild or moderate and included procedural pain and procedural headache, both related to lumbar puncture. Headache, pyrexia, and malaria were also reported.

There was also 38 drug-related treatment-emergent adverse events reported in 14% of patients, all mild or moderate, with the most common being pyrexia and asthenia.

Serious treatment-emergent adverse events were reported in 10% of patients, but none were considered drug-related.

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