At the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Global 2026 conference, Phase III data for Aicuris’s pritelivir, a novel oral helicase primase inhibitor in development for herpes simplex virus (HSV) infections, was presented in an ePoster flash session.
HSV is a virus of the Herpesviridae family. There are two types of HSV. HSV-1 is predominately an orally transmitted infection and causes cold sore wounds around the mouth. HSV-2 is a sexually transmitted infection (STI) and predominately causes genital herpes. Co-infection of both HSV-1 and HSV-2 can also occur. HSV infections are not curable, but antivirals can be used to manage symptoms.
Go deeper with GlobalData
Access deeper industry intelligence
Experience unmatched clarity with a single platform that combines unique data, AI, and human expertise.
The management of HSV infections among immunocompromised patient populations can be particularly challenging as these patients are more prone to severe, prolonged, and refractory HSV infections that do not respond to standard-of-care antivirals such as acyclovir. Refractory infections are associated with substantial quality-of-life and psychosocial impacts, and can lead to dissemination and hospitalisation. Treatment options for ACV-refractory patients are typically limited to foscarnet, an antiviral associated with suboptimal efficacy, intravenous (IV) administration burden, and treatment-limiting toxicities; or off-label therapies. Consequently, there is a very high unmet need for novel therapies that are more effective and better tolerated.
Pritelivir is a first-in-class small molecule drug that targets the viral helicase-primase complex. The drug candidate has demonstrated activity against nucleoside analogue and foscarnet-resistant HSV-1 and HSV-2 isolates in vitro. It is also orally bioavailable with a half-life of approximately 60 days, allowing for once-daily dosing. Additionally, studies demonstrate that pritelivir does not exhibit clinically relevant drug-drug interactions.
PRIOH-1 was a randomised, open-label Phase III trial that investigated the efficacy and safety of pritelivir compared to investigator’s choice treatment (ICT)—foscarnet IV, imiquimod topical, cidofovir IV, or cidofovir topical—administered in a 1:1 ratio in 101 immunocompromised adults with acyclovir-refractory mucocutaneous HSV infections, with or without resistance (R±R). Key inclusion criteria included evidence of clinical failure (no clinical improvement in HSV lesion(s) after treatment with either acyclovir, valacyclovir, or famciclovir for at least seven days), or laboratory confirmed genotypic/phenotypic acyclovir resistance. Underlying causes of the subjects’ immunocompromised state included haematological malignancies and disorders, haematopoietic cell transplantation (HCT), HIV infection, autoimmune/inflammatory diseases, non-haematological malignancies, and solid organ transplants.
The study met its primary endpoint with pritelivir achieving statistically significantly higher rates of complete lesion healing up to 28 days of treatment compared to ICT (62.7% and 34.0%, respectively), equating to an adjusted treatment difference of 28.4% (p=0.0047). Treatment effects and response rates also increased further up to 48 days of treatment. Complete lesion healing was achieved in 82.4% of patients treated with pritelivir compared to 42.0% of patients treated with ICT, equating to an adjusted treatment difference of 40.2% (p>0.0001).
Additionally, a post-hoc analysis found that the percentage of patients with cessation of HSV DNA detection was 73.7% in the pritelivir group compared to 48.7% in the ICT group, equating to an adjusted treatment difference of 25% (p=0.0251).
Pritelivir also demonstrated a favorable safety and tolerability profile compared to ICT. The number of subjects who experienced drug-related treatment-emergent adverse events (TEAEs) was 11 (21.6%) in the pritelivir group compared to 27 (54.0%) in the ICT group. Furthermore, serious TEAEs occurred in 10 (19.6%) subjects in the pritelivir group compared to 15 (30.0%) subjects in the ICT group, while treatment discontinuations due to drug-related TEAEs occurred in one (2.0%) subject in the pritelivir group and 10 (20.0%) subjects in the ICT group. TEAEs of special interest, including those relating to electrolyte abnormalities, renal and urinary disorders, skin disorders, and haematological events, all occurred at lower rates in the pritelivir group compared to the ICT group.
Pritelivir is currently at the pre-registration stage of development in the US. The FDA granted priority review for the new drug application (NDA) for pritelivir in April 2026, and has set a Prescription Drug User Fee Act (PDUFA) target date for Q4 2026, indicating that the drug could be available in this market within the next year. The PRIOH-1 trial has demonstrated that pritelivir’s clinical profile is far superior to that of current standard-of-care therapies used to manage immunocompromised patients with refractory HSV infections, based on multiple parameters. The drug candidate is expected to be a game-changer for these patients, providing them with safer, more convenient, and more effective means to manage their symptoms. Additionally, due to improved cancer treatments and other medical advances, the proportion of the global population that is immunocompromised is likely to continue to increase in the near future, culminating in an expanding target patient population for pritelivir.
