Pritelivir efficacy and safety
1 evidence topic · 18 sources
Summary
- Design: PRIOH-1 Part C (NCT03073967) was a phase 3, randomized, open-label comparison of oral pritelivir (400 mg on day 1, then 100 mg once daily) with investigator's choice (intravenous foscarnet in 70% of that arm; otherwise cidofovir or topical imiquimod) for up to 28 days, or 42 days if lesions were improving, in immunocompromised adults with mucocutaneous HSV infection refractory to acyclovir, valacyclovir, or famciclovir, with or without documented resistance. Of 102 participants randomized, 101 were treated (51 pritelivir, 50 investigator's choice). The registry lists 70 locations and an enrollment of 158; other sources print 153 or 157 participants, 60 or 66 sites, and 12, 14, or 15 countries.
- Primary efficacy: in the prescribing information, all lesions healed within 28 days in 32 of 51 participants (63%) on pritelivir and 17 of 50 (34%) on investigator's choice (adjusted difference 28.4; 95% CI 9.6 to 47.3; p = 0.0047). The congress presentations print 62.7% and 34.0% with the same adjusted difference, confidence interval, and P value.
- Secondary and subgroup results: healing up to day 42 was 82% and 42% in the label (adjusted difference 40%; 95% CI 22.7 to 57.7); the congress presentation prints 82.4%, 42.0%, and 40.2% (p<0.0001). Median time to undetectable HSV DNA in lesions was 9 and 21 days (hazard ratio 1.76; 95% CI 0.98 to 3.16; p = 0.0581). Day 28 healing was 14 of 23 (61%) and 3 of 15 (20%) among all participants living with HIV, a post hoc analysis (p = 0.027); 8 of 16 (50.0%) and 11 of 28 (39.3%) among transplant recipients; and 11 of 22 (50.0%) and 10 of 34 (29.4%) with laboratory-confirmed acyclovir resistance. The 95% CI of the difference includes zero in the last two subgroups.
- Parts D to F and phase 2: single-arm Parts D and F enrolled 35 participants refractory to acyclovir and foscarnet or foscarnet intolerant; lesions healed in 40% up to 28 days and 66% up to 42 days. Part E treated 21 participants with acyclovir-sensitive infection; no result was found. Phase 2 Part A randomized 22 participants to pritelivir (15) or intravenous foscarnet (7): the hazard ratio for the primary endpoint, time to healing by independent photographic review, was 2.70 (P = .34), and investigators recorded healing in 14 of 15 (93.3%) and 4 of 7 (57.1%). In open-label Part B, 5 of 8 participants (62.5%) healed.
- Safety: in the label, headache was the adverse reaction in more than 5% of pritelivir recipients (6%, and 4% on investigator's choice); adverse reactions occurred in 22% and 54%, and discontinuations due to adverse drug reactions in 2% and 20%. The congress presentation reports serious adverse events in 10 (19.6%) and 15 (30.0%) and renal or urinary disorders in 3 (5.9%) and 13 (26.0%). The label lists no contraindications and one warning: certain acid-reducing agents may reduce pritelivir exposure. It reports pUL5 substitutions with reduced susceptibility in 4 phase 3 participants and 1 phase 2 participant.
- Other populations and clinical pharmacology: in adults with genital HSV-2, the placebo-controlled trial AIC316-01-II-01 (156 randomized) found shedding rates of 16.6% with placebo and 2.1% with pritelivir 75 mg daily (relative risk 0.13). The crossover trial AIC316-01-II-02 detected HSV in 2.4% of swabs on pritelivir 100 mg and 5.3% on valacyclovir 500 mg (relative risk 0.42); it randomized 91 of 98 planned participants and was terminated after the FDA imposed a clinical hold in May 2013, based on hematologic and dermatologic findings in a chronic toxicity study in monkeys. In the thorough QT trial, the placebo-corrected QTcF change predicted at the mean maximum concentration was 0.8 ms (90% CI -1.3 to 2.9). Esomeprazole 40 mg decreased pritelivir AUC by approximately 59%, and pritelivir increased rosuvastatin AUC 1.4-fold. The label recommends no dose adjustment in mild to severe renal impairment or in mild or moderate hepatic impairment.
- Evidence gaps: as of October 2026, no full peer-reviewed publication of Part C was found, and the registry has no posted results. Part C was open-label with investigator-assessed healing, and 23 of 50 comparator participants (46%) did not complete treatment. No evidence was found for time to lesion healing, recurrence, pain, or quality-of-life results in Part C, or for any Part E result. Participants with ocular, central nervous system, or disseminated HSV disease were not enrolled.