FDA Approves Hovilpri (Pritelivir): First-of-Its-Kind Helicase-Primase Inhibitor for Refractory HSV in Immunocompromised Adults

FDA Approves Hovilpri (Pritelivir): First-of-Its-Kind Helicase-Primase Inhibitor for Refractory HSV in Immunocompromised Adults

October 9–10, 2026. The FDA has approved pritelivir (HOVILPRI; Asahi Kasei Therapeutics) tablets for mucocutaneous herpes simplex virus (HSV) lesions refractory to standard antiviral treatment — with or without documented resistance to acyclovir, valacyclovir, or famciclovir — in immunocompromised adults. Pritelivir is a helicase-primase inhibitor, "a mechanism distinct from nucleoside analogues, which require activation by viral thymidine kinase," and is active against HSV-1 and HSV-2 "including strains resistant to nucleoside analogues and foscarnet." Developed by AiCuris and granted priority review, the drug is expected to be available in the US before the end of 2026.

This is the first approval of a genuinely new mechanism for HSV — nucleoside analogues (acyclovir and descendants) have been the backbone of HSV therapy since the early 1980s¹, leaving refractory patients with only IV foscarnet or cidofovir, both nephrotoxic.

The evidence — PRIOH-1 part C (NCT03073967): a randomized, open-label, comparator-controlled Phase 3 superiority trial in 101 immunocompromised adults with refractory mucocutaneous HSV. Pritelivir (400 mg day 1, then 100 mg daily up to 28 days, extendable to 42) produced:

• Complete healing of all lesions by day 28: 63% vs 34% for investigator's choice (IV foscarnet, IV/topical cidofovir, or topical imiquimod) — adjusted difference 28.4% (95% CI 9.6–47.3; P = .0047)
• Lesion response through day 42: 82% vs 42% (adjusted difference 40.0%)
• Adverse reactions 22% vs 54%; discontinuations 2% vs 20%; headache most common (6% vs 4%). No boxed warning described.

Why it matters: Genovefa Papanicolaou, MD, of Memorial Sloan Kettering, a PRIOH-1 investigator, framed the unmet need in the approval announcement: "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." Asahi Kasei US/Europe CEO Stacy Wheeler called HOVILPRI "a new oral treatment option for adult patients with a persistent, difficult-to-treat disease."

Practical caveats from the label: acid-reducing agents (PPIs) can lower pritelivir exposure — esomeprazole and rabeprazole should be avoided, omeprazole/lansoprazole capped at 20 mg/day, pantoprazole at 40 mg/day — and pritelivir inhibits BCRP, raising levels of BCRP-substrate drugs.