FDA Approves Pritelivir for Refractory HSV Lesions in Immunocompromised Adults

The FDA approved pritelivir (Hovilpri; Asahi Kasei Therapeutics) tablets for immunocompromised adults with mucocutaneous lesions caused by herpes simplex virus (HSV) infection that has not responded to acyclovir, valacyclovir, or famciclovir. The October 9, 2026, approval introduces an oral option for patients whose persistent infections can complicate cancer treatment or transplantation care. The indication includes refractory infection with or without documented antiviral resistance.^1,2

For pharmacists, the immediate practice consideration is medication review: certain acid-reducing medicines can decrease pritelivir exposure, jeopardizing its effectiveness. The approval also brings renewed attention to recognizing treatment failure in patients with weakened immune systems, particularly when lesions remain unresolved despite conventional antiviral therapy.^1,2

Addressing a Difficult Treatment Gap

HSV-1 and HSV-2 establish lifelong infections. Although antiviral medicines help control outbreaks, they do not eliminate latent virus. Immunocompromised patients can experience more frequent or severe episodes, with painful lesions involving the skin or mucosal surfaces. Resistance to existing treatments can make those episodes difficult to resolve.¹

The clinical challenge extends beyond switching between familiar oral antivirals. CDC guidance explains that acyclovir-resistant HSV strains are also resistant to valacyclovir, and most are resistant to famciclovir. Its guidance recommends infectious disease consultation for suspected resistant infection and identifies intravenous foscarnet as a treatment for acyclovir-resistant genital herpes. Foscarnet and cidofovir carry nephrotoxicity risks and require intensive laboratory monitoring.³

A multicenter retrospective study of foscarnet illustrates that burden. Among 31 HSV treatment episodes in immunocompromised adults, 15 resolved during or after therapy. Electrolyte disturbances occurred in 65% of episodes and kidney dysfunction in 42%; adverse events led to foscarnet discontinuation in 32%. These observational findings provide context for the need for alternatives, rather than a direct comparison with pritelivir.⁴

Pritelivir targets the HSV helicase-primase complex, which participates in viral DNA replication. This differs from the viral DNA polymerase target of nucleoside analogue therapies and provides a distinct approach to infections that have not responded to those agents.⁵

PRIOH-1 Demonstrates Improved Lesion Healing

The approval was supported by Part C of PRIOH-1 (NCT03073967), a phase 3 randomized, open-label, comparator-controlled superiority trial. Investigators randomly assigned and treated 101 immunocompromised adults with mucocutaneous HSV infection unresponsive to conventional antiviral therapy.¹

The study included patients with hematologic malignancies or disorders and recipients of hematopoietic stem-cell transplants. Other participants had HIV infection, autoimmune or inflammatory conditions, nonhematologic malignancies, or solid-organ transplants. This range of underlying conditions makes the findings relevant to pharmacists working across oncology and transplant services.¹

Participants received pritelivir or investigator-selected treatment for up to 28 days, stopping when all mucocutaneous lesions had healed. Treatment could continue to 42 days when lesions were improving but remained incompletely healed at day 28. The primary end point was complete healing of all lesions during the first 28 days.¹

Complete lesion healing occurred in 63% of pritelivir recipients compared with 34% of those receiving investigator-selected therapy. The manufacturer reported an adjusted treatment difference of 28.4 percentage points (95% CI, 9.6–47.3; P = .0047).^1,2

The endpoint measures resolution of the treated lesions, rather than eradication of HSV. The trial was open-label and compared pritelivir with investigator-selected treatments, which should guide interpretation of the results. Its findings apply to the studied immunocompromised population with refractory mucocutaneous disease.¹

Pharmacists Can Help Protect Treatment Effectiveness

Headache was the most common adverse reaction identified by the FDA. The agency also highlighted drug interactions, making reconciliation of prescription and over-the-counter medicines an important implementation step.¹

The manufacturer’s safety information advises avoiding certain proton pump inhibitor regimens. Pritelivir should be taken at least 2 hours before or 12 hours after H2-receptor antagonists, and at least 2 hours before or after antacids. Pritelivir also inhibits breast cancer resistance protein, potentially increasing exposure to medications that are substrates of this transporter.²

These findings support a practical pharmacist role in checking acid-suppressive therapy and explaining administration timing. Pharmacists can also help patients understand that lesion healing does not cure HSV and that persistent lesions warrant reassessment with the treating team. For oncology and transplant practices, the approval creates another treatment pathway for refractory infection while underscoring the importance of coordinated medication management.^1,3

REFERENCES

1. FDA approves drug to treat lesions caused by herpes simplex virus. News release. FDA. October 9, 2026. Accessed October 12, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-treat-lesions-caused-herpes-simplex-virus

2. 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 12, 2026.

3. Genital herpes. Sexually transmitted infections treatment guidelines. CDC. Reviewed September 21, 2022. Accessed October 12, 2026. https://www.cdc.gov/std/treatment-guidelines/herpes.htm

4. Hammond SP, Rangaraju M, Sumner M, Timmler B, Chandrasekar P, Avery RK. A multicenter assessment of the outcomes and toxicities of foscarnet for treatment of acyclovir-resistant mucocutaneous herpes simplex in immunocompromised patients. Open Forum Infect Dis. 2024;11(3):ofae046. doi:10.1093/ofid/ofae046

5. Birkmann A, Bonsmann S, Kropeit D, et al. Discovery, chemistry, and preclinical development of pritelivir, a novel treatment option for acyclovir-resistant herpes simplex virus infections. J Med Chem. 2022;65(20):13614-13628. doi:10.1021/acs.jmedchem.2c00668