Emodepside takes on hookworm infections with high efficacy but increased AEs

Emodepside appears to be efficacious in the treatment of hookworm infections, with cure rates that surpass those achieved with albendazole but at the expense of increased adverse events (AEs), as shown in a phase IIb study.

In a cohort of adults and adolescents (age 12–60 years) with confirmed hookworm infection who were recruited from four endemic villages and three secondary schools in Pemba Island, Tanzania, the observed cure rate was 96.6 percent with emodepside as opposed to 81.2 percent with albendazole. Emodepside increased the odds of achieving cure by 86 percent (odds ratio [OR], 0.14, 95 percent confidence interval [CI], 0.04-0.35; p=0.0001). [Lancet 2024;404:683-691]

Emodepside also showed greater efficacy against T. trichiura infections, with an observed cure rate of 98 percent compared with only 26 percent with albendazole. Meanwhile, no difference in efficacy against A. lumbricoides infections was documented, with cure rates of 100 percent in both treatment arms.

However, more patients in the emodepside arm than in the albendazole arm had at least one AE (79 percent vs 42 percent), the investigators pointed out.

Vision blur was the most frequently reported AE in the emodepside arm, occurring in 39 percent of participants at the 3-hour assessment and in 38 percent at the 24-hour assessment. This was followed by headache and dizziness at the 3-hour assessment (38 percent and 30 percent, respectively).

In the albendazole arm, headache and dizziness at the 3-hour assessment occurred in 18 percent and 10 percent of participants, respectively.

Most AEs in both treatment arms were mild, and none of the patients had serious AEs.

Emodepside has been shown to interact with SLO-1, a calcium-activated potassium channel, which is expressed in human cranial arteries and the trigeminal pathway. The investigators highlighted the value of exploring how emodepside might interact with such pathways, considering that a majority of the AEs from emodepside were vestibular or ocular in nature. [Basic Clin Pharmacol Toxicol 2022;131:347-354; Cephalalgia 2009;29:1242-1258; Cell Tissue Res 2008;334:359-369]

Additionally, in unpublished preclinical studies, emodepside treatment resulted in slight, dose-dependent elevations in blood glucose, the investigators noted, adding that whether drug-induced glucose changes have perceivable effects on vision should also be studied.

Overall, the findings “confirm the findings from the phase IIa clinical trial, solidifying emodepside as a promising candidate to move forward in development for the treatment of soil-transmitted helminth infections. With its excellent efficacy and satisfactory safety profile, emodepside could be used for individual case management, or be implemented into helminthiases control programmes to reach elimination,” they said. [N Engl J Med 2023;388:1863-1875]

A total of 293 patients participated in the phase IIb trial. These patients were randomly assigned to receive treatment with either 30 mg of emodepside (n=146, mean age 22.9 years, 68 percent female) or 400 mg of albendazole (n=147, mean age 24.5 years, 71 percent female), administered once orally. In the entire population, 96 percent had light intensity hookworm infection, and 91 percent were co-infected with another soil-transmitted helminth species.