Pritelivir, a new oral therapy, was significantly more effective against herpes simplex virus (HSV) than a comparator treatment for immunocompromised patients with refractory infections, based on data from 101 individuals. The findings were presented at the Tandem Meeting of the American Society for Transplantation and Cellular Therapy and CIBMTR.

Treatment options for HSV types 1 and 2 in immunocompromised patients are limited, but pritelivir offers a distinct mechanism of action by targeting the HSV helicase-primase complex, blocking viral DNA, and targeting both HSV-1 and HSV-2, according to Cynthia Wat, MD, chief medical officer for Aicuris, the drug’s manufacturer.

“HSV infections refractory or resistant to nucleoside analogs are increased in immunocompromised patients who have increased use of standard-of-care HSV nucleoside analogs for either treatments or for prophylaxis,” Wat told Medscape Medical News.

The only currently FDA-approved treatment after failure of standard-of-care nucleoside analog therapy is foscarnet, a pyrophosphate analog, but the drug is associated with a range of side effects that cause many patients to discontinue treatment. These side effects include granulocytopenia, anemia, hypokalemia, hypocalcemia, hypomagnesemia, paresthesia, rash, chills, fluid overload, increased blood creatinine, and decreased hemoglobin. The need for intravenous (IV) administration further complicates foscarnet treatment, Wat said. By contrast, pritelivir is given orally, and preliminary phase 3 data released by the company in October 2025 showed effectiveness and favorable tolerability.

In the study, researchers randomized 101 immunocompromised patients aged 16 years or older with HSV mucocutaneous infection, with or without resistance, to receive either oral pritelivir (100 mg daily after a 400-mg loading dose) or the investigator’s choice of IV foscarnet, IV or topical cidofovir, or topical imiquimod for up to 28 days, with potential extension to 42 days.

Patients were immunocompromised from conditions including organ transplant (43.6%); oncology and other indications (such as autoimmune diseases, primary immunodeficiency disorders, and the use of chronic immunosuppressive agents) (33.7%); and HIV infection (22.8%). Most of the patients (71.3%) had refractory HSV, and 28.7% had acyclovir-resistant infections. The mean age of the patients was 52.6 years, and 52.5% were men.

The primary endpoint was complete lesion healing within 28 days. Overall, 62.7% of patients treated with pritelivir achieved the primary endpoint, compared with 34% of patients randomized to the comparison treatments, for a significant adjusted treatment difference of 28.4% (P = 0.0047). Most of the adverse events were less common in the pritelivir patients than in other patients. Notably, pritelivir was associated with significantly fewer renal problems, electrolyte events, and drug-related treatment-discontinuations than comparator treatments (2.0% vs 20.0%). The most common treatment-emergent adverse events were headache, nausea, diarrhea, and vomiting. In addition, seven patients in the comparator group developed hypokalemia, but none of the patients treated with pritelivir did.

The study findings were not fundamentally surprising, but clinically meaningful in magnitude, Wat told Medscape Medical News. “The results are consistent with pritelivir’s novel mechanism of action targeting the helicase-primase complex, so activity against acyclovir- and foscarnet-resistant strains was expected, and initial clinical activity has been demonstrated in otherwise healthy adults with genital HSV-2 infection,” she said. “What is notable is the size and robustness of the effect; the combination of oral dosing, clear efficacy advantage, and fewer drug-related discontinuations makes these results more impactful than earlier, smaller studies suggested,” she added.

The clinical implications of pritelivir include reducing the need for prolonged IV therapy, lowering the risk for renal and electrolyte toxicity, improving treatment outcomes, allowing better outpatient management, and improving patients’ quality of life, Wat told Medscape Medical News. The company is preparing a regulatory filing, with a New Drug Application in the works, so clinicians should watch for labeling, approved indications, and guidance on dosing and monitoring, Wat said.

The study findings were limited by the nature of the current treatments for the study population that prevented direct comparison, Wat noted. The range of treatments with different administrations (oral vs IV) required that the study be open label, although it was randomized, she said. However, the research addresses an unmet need in current clinical practice, Wat added. “The ongoing early access program, which to date has treated over 180 patients who have been dosed with over 320 cycles of treatment, illustrates the value of real-world data, helping healthcare professionals choose the most appropriate pathway for their patients,” she added.

In future studies, focusing on real-world effectiveness and healthcare utilization analyses to evaluate impact on hospitalization rates, IV resource use, and cost effectiveness in transplant and oncology settings would be beneficial, Wat said.

New Options for Vulnerable Patients

Immunocompromised individuals are at an increased risk of developing more severe infections, including atypical infections, and those with HSV are at a higher risk for complications, said Shirin A. Mazumder, MD, an infectious diseases specialist and associate professor at the University of Tennessee Health Science Center in Memphis, Tennessee.

“Alternative therapy options are critical in the treatment of HSV infections, especially for immunocompromised hosts, as antiviral resistance to standard therapy tends to be higher in this group with prolonged use,” said Mazumder, who was not involved in the research. “The current alternative therapies can be associated with significant toxicity, which can limit use,” she added.

If approved, “pritelivir offers a treatment option with a favorable safety profile and superior efficacy,” Mazumder told Medscape Medical News. “Since it is administered orally, it also offers a convenience in administration compared to the IV antivirals currently available,” she added. However, access may be a barrier to use in clinical practice because the drug is new and not standard of care, she noted.

More research is needed to evaluate the resistance potential of pritelivir and the efficacy in the treatment of non-mucocutaneous HSV infections, said Mazumder. Evaluation of efficacy in other patient populations, including pregnant women and people living with HIV, is required as well, she said.

The study was funded by Aicuris. Wat is the chief medical officer for Aicuris. Mazumder reported no financial conflicts.