Amenamevir (ASP2151), a novel, non‐nucleoside analog, antiviral drug, inhibits the enzyme activities of helicase and primase, which are essential for replication of herpes viral genomic DNA. In this phase 3, randomized, double‐blind, placebo‐controlled, multicenter study, the authors investigated the efficacy and safety of a single patient‐initiated dose of amenamevir to treat recurrent herpes labialis. Adult immunocompetent patients with recurrent herpes labialis who had the experience and ability to recognize prodromal symptoms were randomly assigned to administer amenamevir 1200 mg or placebo as a patient‐initiated therapy within 6 hours after onset of prodromal symptoms. The primary efficacy end point was time to healing of all herpes labialis lesions in the modified intention‐to‐treat population. Secondary efficacy end points were time to crusting of all herpes labialis lesions, time to resolution of pain accompanying herpes labialis, proportion of patients with aborted lesions, and time to resolution of subjective symptoms accompanying herpes labialis. The modified intention‐to‐treat population, which excluded patients with aborted lesions, comprised 298 patients who self‐initiated amenamevir and 307 who took placebo. Amenamevir demonstrated superiority over placebo for the primary end point; the median time to all lesion healing was 5.1 days for amenamevir versus 5.5 days for placebo (hazard ratio, 1.24; 95% confidence interval, 1.06–1.46; p = 0.0085). Time to crusting of all lesions was significantly shorter with amenamevir versus placebo (p = 0.0065); there were no significant between‐group differences in other secondary outcomes. Treatment‐emergent adverse events in both groups were generally mild in severity; there were two moderate events that were judged unrelated to study treatment, and no severe or serious events. In summary, a single patient‐initiated dose of amenamevir 1200 mg taken within 6 hours of prodromal symptom onset significantly shortened the time to all lesion healing of recurrent herpes labialis compared with placebo, with no clinically important safety concerns.

Background Amenamevir is a helicase-primase inhibitor with novel mechanisms of anti-herpetic action. A patient-initiated single-dose regimen showed clinical efficacy for genital herpes in a phase 2 study. Methods In this phase 3 study, adult immunocompetent patients with recurrent genital herpes and able to accurately recognize prodromal symptoms were randomly assigned to administer amenamevir 1200 mg or placebo as a patient-initiated therapy within 6 hours after onset of prodromal symptoms. The primary efficacy endpoint was time to healing of all genital herpes lesions. Results In the modified intention-to-treat population, which excluded patients with aborted lesions (amenamevir, n = 89; placebo, n = 97), the median time to all lesion healing was 4.0 days for amenamevir versus 5.1 days for placebo (hazard ratio 1.60; 95% confidence intervals, 1.19–2.15; P = .0018), indicating superiority of amenamevir. All treatment-emergent adverse events in both groups were mild in severity. Conclusions Patient-initiated single-dose amenamevir reduced the time to all lesion healing of recurrent genital herpes versus placebo, with no safety concerns, suggesting it could be an effective treatment option for patients with recurrent genital herpes. Clinical Trial Registration JapicCTI-194955 (https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?clinicalTrialId=33260)