In a phase 3 trial, the novel oral antiviral pritelivir demonstrated superior lesion healing and better tolerability than existing therapies in immunocompromised patients with refractory or resistant herpes simplex virus infections.
This week, German clinical-stage pharmaceutical company, Aicuris, announced positive results from its phase 3 PRIOH-1 trial evaluating its investigational antiviral, pritelivir, in immunocompromised patients with refractory herpes simplex virus (HSV) infections, with or without antiviral resistance. The findings represent a major advance for a patient population with few effective and well-tolerated treatment options and were selected for an oral late breaker presentation at the 2026 Tandem Meetings happening this week in Salt Lake City.
The global, controlled, open-label study (NCT03073967) assessed the efficacy and safety of pritelivir, a first-in-class helicase-primase inhibitor, compared with investigator’s choice therapy (ICT). Current ICT options for refractory HSV—such as intravenous foscarnet, cidofovir, or topical imiquimod—are often limited by toxicity, resistance, and the need for prolonged intravenous administration in healthcare settings.
As previously announced in October 2025, the trial met its primary efficacy endpoint. Pritelivir achieved a statistically significant and clinically meaningful improvement in lesion healing, with 62.7% of patients experiencing healing compared with 34.0% in the ICT group. This translated to an adjusted treatment difference of 28.4% (p = 0.0047), underscoring pritelivir’s superiority in a population at high risk for severe and persistent disease.
Equally notable were the safety and tolerability findings. Patients treated with pritelivir experienced substantially fewer drug-related treatment-emergent adverse events (TEAEs) than those receiving ICT. Discontinuations due to adverse events occurred in just 2.0% of pritelivir-treated patients, compared with 20% in the ICT arm. Renal and electrolyte abnormalities—well-recognized complications of existing therapies—were less frequent with pritelivir. The most commonly reported TEAEs, occurring in at least 5% of patients, included headache, diarrhea, nausea, decreased appetite, vomiting, and dizziness.
“These patients often face poor response rates, significant toxicities, and the burden of daily intravenous infusions,” Genovefa Papanicolaou, MD, clinical director of the Infectious Disease Service at Memorial Sloan Kettering Cancer Center and lead investigator of the study said in a statement. Papanicolaou emphasized that an effective oral agent with fewer side effects could meaningfully improve both clinical outcomes and quality of life for hematopoietic cell transplant recipients and other immunocompromised individuals.
Pritelivir significantly outperformed investigator’s choice therapy in lesion healing among immunocompromised patients with refractory or resistant HSV.
The oral antiviral showed a more favorable safety and tolerability profile, with far fewer treatment discontinuations than existing therapies.
With a novel mechanism of action and activity against resistant strains, pritelivir could redefine care for high-risk patients lacking effective HSV treatment options.
The trial randomized 101 immunocompromised patients with refractory or resistant HSV infections, including recipients of hematopoietic stem-cell or solid organ transplants, patients with malignancies, autoimmune or inflammatory disorders, and individuals living with HIV. An additional 56 patients were treated in a non-randomized cohort. Participants received either oral pritelivir (100 mg daily with a 400 mg loading dose on day one) or ICT for up to 28 days, with the option to extend therapy to 42 days if lesions continued to improve.
Pritelivir is an oral, direct-acting antiviral drug designed to treat herpes simplex virus (HSV-1 and HSV-2). Its distinct mechanism of action differentiates it from currently available antivirals. By inhibiting the HSV helicase-primase complex, it blocks viral DNA synthesis through a pathway independent of nucleoside analogues and foscarnet. This allows activity against resistant strains, addressing a long-standing gap in HSV management. Earlier clinical studies demonstrated favorable safety and early efficacy signals, leading to FDA Breakthrough Therapy designation.
“For more than two decades, there has been no meaningful innovation in HSV antivirals,” Aicuris Chief Medical Officer Cynthia Wat, MD, said in a statement. “These results support pritelivir’s potential to redefine the standard of care for patients at highest risk of morbidity and mortality.”
HSV remains a major global public health burden, with billions infected worldwide and particularly severe consequences in immunocompromised populations. Aicuris expects to file for FDA marketing authorization in the first quarter of 2026, positioning pritelivir as a potential new standard for treating refractory HSV infections.
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