FDA Approves Pritelivir for Refractory Mucocutaneous HSV in Immunocompromised Adults

The US Food and Drug Administration (FDA) has approved pritelivir (HOVILPRI; Asahi Kasei Therapeutics) 100-mg tablets for the treatment of mucocutaneous lesions caused by herpes simplex virus (HSV) infection that is refractory, with or without documented resistance, to acyclovir, valacyclovir, or famciclovir in immunocompromised adults.^1,2

The October 9 approval introduces a new oral treatment option for patients with difficult-to-treat HSV and represents the first FDA-approved HSV therapy with a novel mechanism of action in nearly 30 years. Pritelivir is a helicase-primase inhibitor with activity against HSV-1 and HSV-2, including strains resistant to nucleoside analogues.¹

“Today’s approval delivers the first FDA-approved treatment for refractory mucocutaneous HSV lesions with a novel mechanism of action in nearly 30 years and marks an important advancement for immunocompromised adults,” Stacy Wheeler, chief executive officer of Asahi Kasei Therapeutics in the US and Europe, said in a news release.¹

Phase 3 PRIOH-1 Data

The approval was supported by results from Part C of the pivotal phase 3 PRIOH-1 trial (NCT03073967), a randomized, open-label, comparator-controlled superiority trial evaluating pritelivir among immunocompromised adults with mucocutaneous HSV infection refractory to acyclovir, valacyclovir, or famciclovir, with or without documented resistance.^1,2

The registrational portion included 101 adults with underlying immunocompromising conditions, including hematologic malignancies or disorders, hematopoietic stem cell transplantation, HIV infection, autoimmune or inflammatory diseases, nonhematologic malignancies, and solid organ transplantation.^1,2

Participants received oral pritelivir, administered as a 400-mg loading dose on day 1 followed by 100 mg once daily, or investigator's choice of intravenous foscarnet, intravenous or topical cidofovir, or 5% topical imiquimod. Treatment continued for up to 28 days and could be extended to 42 days in patients whose lesions were improving but had not completely healed.¹

The trial met its primary efficacy end point, with 63% of patients receiving pritelivir achieving complete lesion healing by day 28 compared with 34% of those receiving investigator's choice treatment. The adjusted treatment difference was 28.4% (95% CI, 9.6%-47.3%; P = .0047).^1,2

By day 42, observed complete lesion-healing rates were 82% with pritelivir and 42% with investigator's choice, corresponding to an adjusted treatment difference of 40.0% (95% CI, 22.7%-57.7%).¹

Adverse reactions were reported in 22% of participants treated with pritelivir compared with 54% receiving investigator's choice. Treatment discontinuations due to adverse drug reactions occurred in 2% and 20% of patients, respectively. Headache was the most common adverse reaction, occurring in 6% of patients receiving pritelivir and 4% receiving investigator's choice.¹

Addressing an Unmet Need in Refractory HSV

Although HSV infection may be asymptomatic or relatively mild in immunocompetent adults, immunocompromised patients are at increased risk of more frequent, severe, and treatment-refractory disease. Persistent mucocutaneous HSV lesions can be particularly challenging in patients undergoing transplantation, those with malignancies, people living with HIV, and patients with autoimmune or inflammatory diseases.^1,2

Standard nucleoside analogue antivirals, including acyclovir, require activation by viral thymidine kinase. Mutations affecting the enzyme can reduce viral susceptibility to these therapies. Patients whose infections are refractory to nucleoside analogues have historically had limited alternatives, some of which require intravenous administration.¹

Pritelivir instead inhibits the HSV helicase-primase complex, interfering with viral DNA replication through a mechanism distinct from nucleoside analogue therapies.¹

“In patients with blood cancers or those who have undergone stem cell transplantation, refractory HSV infections can be prolonged, painful, and difficult to treat, while available intravenous treatments carry substantial risks,” Genovefa Papanicolaou, MD, clinical director of the Infectious Disease Service at Memorial Sloan Kettering Cancer Center, professor at Weill Cornell Medical College, and a PRIOH-1 investigator, said in the release.¹

Pritelivir previously received FDA Fast Track and Breakthrough Therapy designations, and its new drug application was granted Priority Review. Asahi Kasei Therapeutics expects HOVILPRI to become available in the US before the end of 2026.^1,2

References

1. Asahi Kasei Therapeutics announces FDA approval of HOVILPRI (pritelivir) tablets for mucocutaneous HSV lesions refractory (with or without resistance) to standard antiviral treatment in immunocompromised adults. News release. Asahi Kasei Therapeutics. October 9, 2026. Accessed October 15, 2026.
2. US Food and Drug Administration. FDA approves drug to treat lesions caused by herpes simplex virus. Published October 9, 2026. Accessed October 15, 2026.