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

Authors

• Camille N. Kotton, Massachusetts General Hospital, Boston, MA
• Kimberly A. Workowski, Emory University, Atlanta, GA
• Princy N. Kumar, Georgetown University Medical Center, Washington, DC
• Robin K. Avery, Johns Hopkins University, Baltimore, MD
• Roy F. Chemaly, University of Texas MD Anderson Cancer Center, Houston, TX
• Nicolas C. Issa, Brigham and Women's Hospital, Boston, MA
• Moti Ramgopal, Midway Immunology and Research Center, Fort Pierce, FL
• Joshua T. Schiffer, Fred Hutchinson Cancer Center, Seattle, WA
• Joerg Albrecht, Cook County Health, Chicago, IL
• Hollis R. O’Neal, LSU Health Sciences Center - New OrleansFollow
• Pranatharthi Chandrasekar, Wayne State University, Detroit, MI
• Tanya S. Schreibman, CAN Community Health, Sarasota, FL
• Mayur Ramesh, Henry Ford Health System, Detroit, MI
• Michael G. Ison, National Institutes of Health, Bethesda, MD
• Melanie E. Sumner, AiCuris Anti-infective Cures AG, Wuppertal, Germany
• Aaron Dane, DaneStat Consulting, Cheshire, United Kingdom
• Bernadette Surujbally, AiCuris Anti-infective Cures AG, Wuppertal, Germany
• Burkhard Timmler, AiCuris Anti-infective Cures AG, Wuppertal, Germany
• Manickam Rangaraju, AiCuris Anti-infective Cures AG, Wuppertal, Germany
• Genofeva A. Papanicolaou, Memorial Sloan Kettering Cancer Center, New York, NY
• Alexander Birkmann, AiCuris Anti-infective Cures AG, Wuppertal, Germany
• Anna Wald, University of Washington, Seattle, WA

Document Type

Article

Publication Date

8-31-2026

Publication Title

Open Forum Infectious Diseases

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

Publisher

Oxford University Press on behalf of Infectious Diseases Society of America

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Kotton, Camille N.; Workowski, Kimberly A.; Kumar, Princy N.; Avery, Robin K.; Chemaly, Roy F.; Issa, Nicolas C.; Ramgopal, Moti; Schiffer, Joshua T.; Albrecht, Joerg; O’Neal, Hollis R.; Chandrasekar, Pranatharthi; Schreibman, Tanya S.; Ramesh, Mayur; Ison, Michael G.; Sumner, Melanie E.; Dane, Aaron; Surujbally, Bernadette; Timmler, Burkhard; Rangaraju, Manickam; Papanicolaou, Genofeva A.; Birkmann, Alexander; and Wald, Anna, "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" (2026). School of Medicine Faculty Publications. 5256.
https://digitalscholar.lsuhsc.edu/som_facpubs/5256
10.1093/ofid/ofag539