Pritelivir Cuts Hospital Days in Refractory HSV in Phase 3 PRIOH-1

Oral pritelivir (AiCuris) achieved complete lesion healing in 62.7% of immunocompromised patients with refractory herpes simplex virus (HSV) infection vs 34.0% with investigator's choice therapy, and it reduced all-cause hospitalizations from 76% to 29.4%.¹ The healthcare resource use data from the phase 3 PRIOH-1 trial were presented by Ryan C. Maves, MD, at IDWeek 2026, held October 21-24 in Washington, DC. A companion poster reported consistent results in a global early access program.²

Foscarnet, the only FDA-approved option for acyclovir-refractory HSV, requires intravenous administration, hydration, and close monitoring for nephrotoxicity.¹ In a retrospective study of hematopoietic cell transplant recipients cited by the investigators, 29.6% of foscarnet or cidofovir courses were discontinued because of toxicity. Pritelivir, a helicase-primase inhibitor, does not require activation by viral thymidine kinase and has a half-life of 60 hours, allowing once-daily oral dosing.^1,2

PRIOH-1 Lesion Healing and Hospitalization Results With Pritelivir

PRIOH-1 randomized 101 immunocompromised adults with refractory HSV, with or without acyclovir resistance, to pritelivir (n = 51) or investigator's choice therapy (n = 50).¹ Pritelivir patients received a 400-mg loading dose followed by 100 mg daily for up to 28 days, extendable to 42 days. Investigator's choice included intravenous foscarnet, intravenous or topical cidofovir, and topical imiquimod.¹

Transplant recipients made up 43.6% of the full analysis set, followed by patients with oncologic, autoimmune, or inflammatory disease (33.7%) and HIV infection (22.8%).¹ Mean age was 52.6 years.¹

Complete lesion healing by day 28 occurred in 62.7% (32/51) of the pritelivir group vs 34.0% (17/50) of the comparator group (P = .0047; 95% CI for difference, 9.6%-47.3%).¹ By day 42, healing rates reached 82.4% (42/51) vs 42.0% (21/50) (P < .0001; 95% CI, 22.7%-57.7%).¹

Pritelivir also shifted treatment out of the hospital, with 92.2% of recipients self-administering the drug while 68% of the comparator group received at least 1 dose in the hospital.¹ All-cause hospitalization occurred in 29.4% (15/51) vs 76% (38/50) of patients, totaling 21 stays and 428 hospital days with pritelivir vs 48 stays and 873 days with investigator's choice.¹

In the US subgroup, 40.7% vs 78.6% of patients were hospitalized, accounting for 189 vs 514 hospital days.¹ Study medication administration itself drove 32.0% of hospitalizations in the comparator arm and none in the pritelivir arm.¹

Pritelivir Safety and Early Access Program Outcomes in Refractory HSV

Drug-related treatment-emergent adverse events occurred in 21.6% of pritelivir recipients vs 54.0% of comparator recipients, and treatment-emergent serious adverse events occurred in 19.6% vs 30.0%.¹ Discontinuation because of drug-related adverse events occurred in 2.0% vs 20.0%. Renal and urinary disorders affected 5.9% vs 26.0% of patients, and hematologic adverse events affected 9.8% vs 28.0%.¹

Exposure-adjusted adverse event rates were 42.8 vs 102.0 events per participant-year, and no pritelivir recipient had hypokalemia vs 14.0% of comparator recipients.¹ Recurrent HSV led to hospitalization in 3.9% of pritelivir recipients and 2.0% of comparator recipients.¹

The early access program enrolled 227 immunocompromised patients with acyclovir- and foscarnet-refractory or foscarnet-intolerant HSV, a group with no approved treatment option.² Among 188 patients in the core efficacy analysis, 44.1% had complete lesion healing by day 28 and 63.8% by day 42, with about 90% healed or improved. Drug-related adverse events occurred in 8.4% of patients, and 6.2% discontinued because of an adverse event.²

Patients in the program ranged in age from 2 to 85 years, and the analysis used a September 2026 data cut.² Safety findings were consistent across second and third treatment courses, given to 70 and 31 patients, respectively.² Treatment-emergent serious adverse events occurred in 17.2% of patients during the first course, in a population with serious underlying immunosuppression.²

The investigators wrote pritelivir has the potential to reduce health care resource utilization by enabling self-administration at home.¹ AiCuris supported both analyses, and several coauthors are company employees.^1,2

References

1. Maves RC, Avery R, Peggs K, et al. Reduced healthcare resource utilization with pritelivir compared to investigator's choice therapy in immunocompromised patients treated for refractory herpes simplex virus: phase 3 PRIOH-1 study. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-28.

2. Lee YJ, Dadwal S, Avery R, et al. Early access program experience of pritelivir in the treatment of acyclovir- and foscarnet-refractory herpes simplex virus infection in immunocompromised patients. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-13.