Pritelivir, a novel helicase-primase inhibitor under investigation by AiCuris, may become a new treatment option for individuals with severe mucocutaneous herpes simplex virus (HSV) infections that are refractory or resistant to acyclovir and foscarnet, according to new data.
“Immunocompromised patients are at high risk for developing recurrent HSV infections that are refractory to acyclovir and other nucleoside analogs,” said Kenneth Lawrence, PharmD, a senior vice president and the head of Medical Affairs at AiCuris U.S., located in Waltham, Mass. “The only FDA-approved treatment for these patients is foscarnet, which is associated with well-known severe toxicities and needs to be administered intravenously in the hospital. Patients with HSV infections that are also resistant or intolerant to foscarnet have only limited off-label treatment options, often associated with efficacy issues or similar safety concerns.”
A New Mechanism
While standard therapy—nucleoside analogs—targets the HSV polymerase, pritelivir targets the viral helicase-primase enzyme complex, which is essential for HSV replication.
“Due to the different mode of action of pritelivir, its potency and oral bioavailability with a long plasma half-life allowing convenient once-daily dosing, pritelivir addresses the limitations of foscarnet and off-label therapies,” Dr. Lawrence said.
83% Full Resolution of HSV Lesions
In the PRIOH-1 phase 2 case series presented at MAD-ID 2025 (abstract 13 E), in Orlando, Fla., 23 immunocompromised patients with acyclovir-refractory HSV infections were treated with pritelivir. The cohort included individuals with HIV infection, malignancies, transplant histories or autoimmune disease. Patients received an initial 400-mg loading dose followed by 100 mg daily for up to 28 days.
Results were encouraging: 19 of 23 patients (83%) achieved full resolution of HSV lesions during the treatment period. The remaining patients experienced partial healing, with several achieving full recovery after the observation window. Pritelivir was well tolerated, with no significant adverse events reported.
“If approved by the FDA, pritelivir will offer a well-tolerated outpatient treatment alternative for patients that require hospitalization when treated with currently approved therapies,” Dr. Lawrence said.
Phase 3 Study Under Way
The strong phase 2 results have propelled pritelivir into late-stage testing, and AiCuris has completed patient enrollment in a pivotal phase 3 trial evaluating pritelivir for the treatment of refractory and/or resistant HSV infection in immunocompromised patients.
“We are focused on preparing for study completion and the data readout and look forward to continuing to explore additional patient populations who may benefit from pritelivir in the future,” Dr. Lawrence said.
Dr. Lawrence reported that he is an employee of AiCuris.