EDP-938 demonstrates efficacy against RSV

Ahmad A, Eze K, Noulin N, Horvathova V, Murray B, Baillet M, et al. EDP-938, a Respiratory Syncytial Virus Inhibitor, in a Human Virus Challenge. N Engl J Med. 2022;386:655-66.QuestionAmong adults artificially infected with respiratory syncytial virus (RSV), what is the therapeutic efficacy of EDP-938 (an RSV replication inhibitor), compared with placebo, in reducing the RSV viral load over a 12-day period?DesignRandomized, controlled, trial.SettingLaboratory setting.ParticipantsAdults, 18-55 years old, intranasally inoculated with RSV-A Memphis 37b.InterventionEDP-938, an RSV nonfusion replication inhibitor or placebo: 600 mg once daily (600 group), 300 mg twice daily after a 500-mg loading dose (300 group), or placebo.OutcomesPrimary: RSV viral load, area under the curve (AUC). Secondary: symptom score.Main ResultsThe mean viral load AUCs and the symptom scores were 204.0 and 125 in the 600 group, 217.7 and 182 in the 300 group, and 790.2 and 479 in the placebo group (statistically significant compared with placebo based on 95% confidence intervals for both EDP-938 groups). EDP-938 and placebo safety profiles were similar.ConclusionsEDP-938 demonstrated viral load reduction and clinical efficacy compared with placebo, with a similar safety profile.CommentaryRSV is a major burden for all infants as well as older adults and certain high-risk groups.1Centers for Disease Control and InfectionRespiratory syncytial virus (RSV): Trends and surveillance.https://www.cdc.gov/rsv/research/us-surveillance.htmlDate accessed: February 15, 2022Google Scholar Presently, treatment is supportive.2American Academy of PediatricsClinical Practice Guideline: The diagnosis, management, and prevention of bronchiolitis.Pediatrics. 2014; 134: e1474-e1502Crossref PubMed Scopus (901) Google Scholar With advances in the understanding of the molecular structure and function of the virus, promising newer approaches to prevention (vaccines and long-acting monoclonal antibodies) and treatment are in development. In this paper, Ahmad et al report a phase 2 trial of EDP-938 (a non-fusion replication inhibitor of RSV) in healthy adult volunteers inoculated with RSV. They demonstrated a good safety profile coupled with decreased viral load, decreased symptom score and decreased mucus production at various dosing ranges of EDP-938 versus placebo. Although these findings are promising, many questions remain before we can say we have an effective antiviral agent for treating RSV disease. As with earlier studies of aerosolized ribavirin, it remains to be seen whether these measures of effectiveness studied will translate to clinical benefits in real world settings.3Ventre K. Randolph A.G. Ribavirin for respiratory syncytial virus infection of the lower respiratory tract in infants and young children.Cochrane Database Syst Rev. 2007; 1: CD000181PubMed Google Scholar Given the study design, volunteers received treatment early in the course of infection and without lower respiratory tract symptoms. It will need be determined whether treatment later in the course of illness and/or with more severe symptoms will be beneficial. Additionally, it will need to be determined whether infants without preexisting immunity, or the elderly, will respond as well or have a similar safety profiles with treatment. Still this report of a promising agent with good antiviral activity and an initially favorable safety profile offers hope for improved treatment of RSV disease and further studies are warranted. Ahmad A, Eze K, Noulin N, Horvathova V, Murray B, Baillet M, et al. EDP-938, a Respiratory Syncytial Virus Inhibitor, in a Human Virus Challenge. N Engl J Med. 2022;386:655-66. QuestionAmong adults artificially infected with respiratory syncytial virus (RSV), what is the therapeutic efficacy of EDP-938 (an RSV replication inhibitor), compared with placebo, in reducing the RSV viral load over a 12-day period? Among adults artificially infected with respiratory syncytial virus (RSV), what is the therapeutic efficacy of EDP-938 (an RSV replication inhibitor), compared with placebo, in reducing the RSV viral load over a 12-day period? DesignRandomized, controlled, trial. Randomized, controlled, trial. SettingLaboratory setting. Laboratory setting. ParticipantsAdults, 18-55 years old, intranasally inoculated with RSV-A Memphis 37b. Adults, 18-55 years old, intranasally inoculated with RSV-A Memphis 37b. InterventionEDP-938, an RSV nonfusion replication inhibitor or placebo: 600 mg once daily (600 group), 300 mg twice daily after a 500-mg loading dose (300 group), or placebo. EDP-938, an RSV nonfusion replication inhibitor or placebo: 600 mg once daily (600 group), 300 mg twice daily after a 500-mg loading dose (300 group), or placebo. OutcomesPrimary: RSV viral load, area under the curve (AUC). Secondary: symptom score. Primary: RSV viral load, area under the curve (AUC). Secondary: symptom score. Main ResultsThe mean viral load AUCs and the symptom scores were 204.0 and 125 in the 600 group, 217.7 and 182 in the 300 group, and 790.2 and 479 in the placebo group (statistically significant compared with placebo based on 95% confidence intervals for both EDP-938 groups). EDP-938 and placebo safety profiles were similar. The mean viral load AUCs and the symptom scores were 204.0 and 125 in the 600 group, 217.7 and 182 in the 300 group, and 790.2 and 479 in the placebo group (statistically significant compared with placebo based on 95% confidence intervals for both EDP-938 groups). EDP-938 and placebo safety profiles were similar. ConclusionsEDP-938 demonstrated viral load reduction and clinical efficacy compared with placebo, with a similar safety profile. EDP-938 demonstrated viral load reduction and clinical efficacy compared with placebo, with a similar safety profile.