Mosnodenvir Prophylaxis Demonstrated in Controlled Dengue Infection Model

Dengue threatens nearly half of the global population, yet no antiviral drug is available for prevention or treatment. 

In the phase 2a, double-blind, randomized trial, healthy adults received oral mosnodenvir once per day at low, medium, or high doses, or a matched placebo. Participants first received loading doses for 5 days, followed by 21 days of maintenance dosing. On day 1, the first day of maintenance dosing, each participant was intentionally exposed to a weakened dengue virus serotype 3 (DENV-3) strain as part of a controlled human infection model. The main goal was to determine how well mosnodenvir reduced viral load, measured as DENV-3 RNA levels from day 1 to day 29.

Results published in the New England Journal of Medicine showed a clear dose-response effect. No participants in the low-dose group and only one in the medium-dose group remained free of DENV-3 infection, while 60% of those receiving the high dose showed no signs of infection. By contrast, none of the placebo recipients avoided infection. The high-dose group showed a significantly lower viral RNA load than the placebo group. Mosnodenvir was generally well tolerated, with no serious side effects. Drug levels rose steadily before virus exposure and remained stable through day 21. Genetic sequencing showed viral mutations in all mosnodenvir-treated participants but none in the placebo group. Overall, high-dose mosnodenvir effectively reduced dengue viral replication without serious safety concerns.

In a controlled human infection model, a high daily dose of oral mosnodenvir significantly reduced DENV-3 viral levels compared with placebo and caused no serious adverse events.

References:

1. Durbin AP, Van Wesenbeeck L, Pierce KK, Herrera-Taracena G, Ebone L, Buelens A, Lutton P, et al. Daily mosnodenvir as dengue prophylaxis in a controlled human infection model. N Engl J Med. 2025;393:2107-18. doi:10.1056/NEJMoa2500179.; https://www.nejm.org/doi/full/10.1056/NEJMoa2500179?query=featured_home