FDA Approves Pritelivir for Acyclovir-Refractory HSV in Immunocompromised Adults. Here Is What the Label Covers.
The FDA approved oral pritelivir (Hovilpri) on Oct. 9 for immunocompromised adults with mucocutaneous HSV lesions refractory to acyclovir-class drugs. In the open-label phase 3 PRIOH-1 trial, 63 percent healed by day 28 versus 34 percent on investigator's choice.
On Oct. 9, the Food and Drug Administration approved pritelivir (Hovilpri, Asahi Kasei Therapeutics), an oral helicase-primase inhibitor, for immunocompromised adults whose mucocutaneous herpes simplex virus lesions have not responded to acyclovir, valacyclovir or famciclovir.
Until now, the options after nucleoside analog failure have been intravenous foscarnet, intravenous or topical cidofovir and topical imiquimod. Those were the comparators in the pivotal trial, and 70 percent of the comparator arm received intravenous foscarnet, according to the prescribing information.
What the label covers
The label limits the indication to immunocompromised adults with mucocutaneous HSV lesions that are refractory, with or without documented resistance, to acyclovir, valacyclovir or famciclovir. It is not an indication for immunocompetent patients or for first-line treatment. The label notes that treatment is not curative, because HSV establishes lifelong latent infection, and safety and efficacy have not been established in pediatric patients.
Pritelivir inhibits the viral helicase-primase complex, a different target from the DNA polymerase inhibited by nucleoside analogs, and the label says cross-resistance with acyclovir, penciclovir or foscarnet is not likely. The company describes it as the first FDA-approved HSV therapy with a novel mechanism of action in nearly 30 years and expects U.S. availability before the end of 2026. It has not announced a price.
What the trial showed
Approval rests on Part C of PRIOH-1 (NCT03073967), a randomized, open-label, comparator-controlled superiority trial in 101 immunocompromised adults. Refractory infection was defined as no clinical improvement after at least 7 days of a nucleoside analog. At enrollment, 71 percent had clinically refractory infection and 29 percent had laboratory-confirmed acyclovir resistance. Patients with ocular, central nervous system or disseminated HSV were not enrolled.
Underlying conditions included hematologic malignancy (47 percent), hematopoietic stem-cell transplantation (40 percent), HIV infection (38 percent), autoimmune or inflammatory disease (29 percent), nonhematologic malignancy (26 percent) and solid organ transplantation (4 percent).
The primary endpoint was the proportion of patients with all lesions healed by day 28. Per the label, 63 percent of pritelivir patients (32 of 51) healed, compared with 34 percent (17 of 50) on investigator's choice, an adjusted difference of 28.4 percentage points (95% CI, 9.6 to 47.3; p=0.0047). Treatment could be extended to 42 days if lesions were improving; by day 42, response rates were 82 percent and 42 percent.
The comparator was mostly intravenous foscarnet, and the trial was open-label. Read both the healing advantage and the tolerability gap with that in mind.
Dosing and warnings
The label dose is a 400 mg loading dose (four 100 mg tablets) on day 1, then 100 mg once daily until lesions have healed. In the trial, mean treatment duration was 27.1 days. Adverse reactions occurred in 22 percent of patients on pritelivir and 54 percent on investigator's choice, and discontinuations for adverse reactions were 2 percent versus 20 percent. Headache was the only reaction above 5 percent, at 6 percent versus 4 percent. ALT elevations of at least 2.5 times the upper limit of normal occurred in 8 percent of pritelivir patients and 2 percent of comparator patients.
The one warning concerns acid-reducing drugs, which can lower pritelivir exposure and may reduce effect and promote resistance. The label says to avoid esomeprazole and rabeprazole, omeprazole or lansoprazole above 20 mg daily and pantoprazole above 40 mg daily. Pritelivir should be taken 2 hours before or 12 hours after an H2-receptor antagonist and separated from antacids by 2 hours. Pritelivir also inhibits breast cancer resistance protein, so substrates of that transporter may reach higher concentrations. No dose adjustment is recommended for renal impairment or for mild or moderate hepatic impairment.
What it means in clinic
Transplant, oncology, HIV and dermatology clinicians can consider pritelivir after documented clinical failure of an acyclovir-class drug, where the alternative would be foscarnet or cidofovir. The indication does not require genotypic resistance testing.
The practical step before launch is a medication review. Ask pharmacy to flag which patients with recurrent HSV take proton pump inhibitors above the label thresholds or transporter substrates, since stepping down a PPI may be part of the plan, and agree on an approach with infectious disease colleagues before the first prescription arrives.
Reported, fact-checked and edited by The Script Pad's editorial staff.
This article is for professional education and does not replace clinical judgment. Treatment decisions should be based on the individual patient and current guidelines.
