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

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) with 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 end point was time to lesion healing; secondary end points included healing rate, HSV DNA detection, and resistance. RESULTS: Twenty-two participants enrolled in Part A, 8 in Part B. In Part A, median time to healing was 26.0 days (95% CI, 13.0-31.0) with pritelivir, vs not estimable (95% CI, 20.0-NE) with foscarnet (HR, 2.7; 95% CI, 0.33-21.8; P = .34). Investigator-assessed healing rates were 93% with pritelivir and 57% with foscarnet, a 36.2% difference (95% CI, -10.1 to 74.1; P = .077). Postbaseline HSV DNA detection rates were 34.8% and 50.0%, respectively (P = .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, the 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.