The following is a summary of “EDP-938 has a high barrier to resistance in healthy adults experimentally infected with respiratory syncytial virus” published in the October 2024 issue of Infectious Disease by Levene et al.
EDP-938, an oral Respiratory syncytial virus (RSV) nucleoprotein inhibitor, exhibited potent antiviral activity in a human RSV, reducing the viral load and symptom severity.
Researchers conducted a retrospective study to examine the development of viral resistance to EDP-938 in a human challenge trial, following in vitro studies suggesting a higher barrier to resistance compared to RSV fusion inhibitors.
They selected 124 participants infected with RSV and analyzed 159 nasal wash samples from 48 participants using next-generation sequencing of the RSV N gene; from 48 participants sampled, 37 were from the EDP-938 treatment group, and 11 were from the placebo group, representing 45% and 26% of the participants, respectively and assessed the impact of treatment-emergent mutations on viral load, EDP-938 efficacy, and viral fitness.
The results showed that 2 of the 37 EDP-938-treated participants with sequenced samples had treatment-emergent mutations: N:L139I and N:E112G. In vitro analysis revealed that N:L139I reduced sensitivity to EDP-938 by approximately 10-fold, while N:E112G had no effect. However, N:L139I was associated with a reduction in viral fitness, suggesting that clinical resistance is associated with fitness costs with none of the variants associated with reduced viral clearance.
They concluded the human RSV infections treated with EDP-938, the emergence of RSV variants with reduced sensitivity to the drug was rare and associated with decreased viral fitness, emphasizing EDP-938’s mechanism of action and high barrier to resistance.
Source: academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiae471/7824591
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