Efficacy and Safety of Pritelivir Versus Foscarnet for the Treatment of Acyclovir-Refractory Herpes Simplex Virus Infection in Immunocompromised Adults: A Randomized, Open-Label Phase 2 Trial

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Abstract Background Immunocompromised patients are at risk for severe, prolonged herpes simplex virus (HSV) recurrences. Refractory disease and intolerance to standard therapy drive an unmet medical need. Pritelivir, a novel HSV helicase-primase inhibitor, has shown favorable tolerability and efficacy in immunocompetent adults. Methods PRIOH-1, a multicenter, randomized, open-label Phase 2 trial compared oral pritelivir (400 mg loading dose followed by 100 mg daily) versus intravenous foscarnet (40 mg/kg q8h or 60 mg/kg q12h) for up to 28 days in immunocompromised adults with acyclovir-refractory HSV (Part A). Participants with refractoriness/intolerance to foscarnet received pritelivir (Part B). The primary endpoint was time to lesion healing; secondary endpoints included healing rate, HSV DNA detection, and resistance. Results Twenty-two participants enrolled in Part A, eight in Part B. In Part A, median time to healing was 26.0 days (95% CI 13.0–31.0) with pritelivir, versus not estimable (95% CI 20.0–NE) with foscarnet (HR 2.7, 95% CI 0.33–21.8; p=0.34). Investigator-assessed healing rates were 93% with pritelivir, 57% with foscarnet; a 36.2% difference (95% CI -10.1–74.1; p=0.077). Post-baseline HSV DNA detection rates were 34.8% and 50.0%, respectively (p=0.42). Treatment-emergent adverse events occurred in 60% of pritelivir- and 100% of foscarnet-treated participants; serious treatment-emergent adverse events were less frequent with pritelivir. In Part B, median time to healing was 19.0 days with a 63% healing rate. Conclusions Pritelivir demonstrated encouraging efficacy and favorable safety in immunocompromised adults with limited treatment options, supporting Phase 3 evaluation for the treatment of refractory HSV infection in this population.