Phase 3 trial confirms superior efficacy of oral pritelivir for refractory HSV in immunocompromised patients

AiCuris Anti-infective Cures AG announced that its registrational Phase 3 trial (PRIOH-1, NCT03073967) of pritelivir, a first-in-class helicase-primase inhibitor for herpes simplex virus (HSV), met its primary endpoint of superiority (p=0.0047) in lesion healing for patients treated up to 28 days. Efficacy further improved in patients treated for up to 42 days (p<0.0001).

The study evaluated pritelivir’s efficacy and safety compared to standard of care (SoC)—including investigator-selected foscarnet, cidofovir, compounded topical cidofovir, or imiquimod—in immunocompromised patients with refractory HSV infections, with or without resistance (R±R) to existing antivirals.

“As a clinician who treats immunocompromised patients, I see these results as a major step forward,” Genovefa Papanicolaou, MD, clinical director of the Infectious Disease Service at Memorial Sloan Kettering Cancer Center and Professor at Weill Cornell College of Medicine, said in a statement. “There has been no HSV treatment innovation for decades. Pritelivir’s oral availability and safety profile could be life-changing—particularly for R±R patients.”

Pritelivir is a small-molecule antiviral that targets the HSV helicase-primase complex through a novel mechanism of action independent of viral enzyme activation, enabling efficacy against strains resistant to acyclovir, valacyclovir, famciclovir, or foscarnet. Immunocompromised patients frequently experience severe, prolonged, and treatment-refractory HSV outbreaks, often requiring intravenous therapies that can cause kidney toxicity, electrolyte imbalances, and hospitalization.

With its superior efficacy, favorable safety profile, and convenient oral dosing, pritelivir represents a potential breakthrough for patients facing limited treatment options.

“Refractory HSV infections remain a significant challenge for patients with weakened immune systems,” Cynthia Wat, MD, chief medical officer at AiCuris, said in a statement. “Pritelivir’s strong efficacy, oral convenience, and safety profile demonstrated in PRIOH-1 could mark a paradigm shift in care. We are deeply grateful to the patients and investigators who made this milestone possible.”

Trial Parameters

The open-label, multicenter trial (NCT03073967 / Eudra-CT 2023-510088-37-00) enrolled 158 immunocompromised patients across 15 countries. Participants received an initial 400 mg loading dose of pritelivir, followed by 100 mg daily until complete lesion healing.

Among the 102 randomized R±R patients, pritelivir was compared 1:1 with investigator’s choice of SoC to assess lesion healing rates and safety. Two additional non-randomized cohorts included 35 patients resistant or intolerant to both acyclovir and foscarnet and 21 acyclovir-sensitive patients, all treated with pritelivir.

About the Therapy

Pritelivir, a novel helicase-primase inhibitor developed by Aicuris, targets both HSV-1 and HSV-2. These viruses are responsible for genital, oral or disseminated infections with increasing severity that are often difficult to treat with a higher risk of resistance development in immunocompromised people.

Unlike traditional antivirals, pritelivir blocks viral DNA synthesis by inhibiting the helicase-primase complex, a mechanism distinct from marketed nucleoside analogues. Because of this distinct mode of action, pritelivir is active against viral strains that are resistant to nucleoside analogs. Earlier trials in immunocompetent and immunocompromised individuals showed a favorable safety profile and early signs of clinical efficacy compared to standard-of-care treatments like valacyclovir and foscarnet. Based on the earlier clinical trial results, pritelivir received FDA breakthrough designation. In July, the last patient was enrolled in the Phase 3 pivotal trial, the outcomes of which are expected to serve as a basis for filing for marketing authorization in 2026.

Reference

Aicuris Announces Pritelivir Met Primary Endpoint in Immunocompromised Patients with Refractory Herpes Simplex Virus in Phase 3 Pivotal Trial. Biospace press release. October 16, 2025. Accessed October 16, 2025.
https://www.biospace.com/press-releases/aicuris-announces-pritelivir-met-primary-endpoint-in-immunocompromised-patients-with-refractory-herpes-simplex-virus-in-phase-3-pivotal-trial