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
Recommended Citation
Kotton CN, Workowski KA, Kumar PN, Avery RK, Chemaly RF, Issa NC, Ramgopal M, Schiffer JT, Albrecht J, O’Neal HR, Jr., Chandrasekar P, Schreibman TS, Ramesh M, Ison MG, Sumner ME, Dane A, Surujbally B, Timmler B, Rangaraju M, Papanicolaou GA, Birkmann A, Wald A. 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. Open Forum Infect Dis. 2026;13(9):539.
Document Type
Article
Publication Date
9-1-2026
Publication Title
Open Forum Infect Dis
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) 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.
PubMed ID
42751311
Volume
13
Issue
9
First Page
539
