Summary

Pritelivir is indicated for immunocompromised adults with mucocutaneous HSV lesions refractory, with or without documented resistance, to acyclovir, valacyclovir, or famciclovir. The indication follows failure of a nucleoside analogue; PRIOH-1 Part C defined failure as no clinical improvement after at least 7 days. It is an oral tablet taken once daily until lesions heal. Part C compared it with investigator's choice of intravenous foscarnet (70% of 50 participants), topical imiquimod (14%), intravenous cidofovir (12%), or topical cidofovir (4%). Parts D and F enrolled 35 participants refractory to or intolerant of foscarnet. Trial investigators state that intravenous foscarnet “requires hospitalization for monitoring and administration”. NIH and hematopoietic cell transplant guidelines name foscarnet as the treatment of choice for acyclovir-resistant HSV, and the CDC guideline names it for acyclovir-resistant genital herpes. The NIH and transplant guidelines list cidofovir as an alternative. The NIH guideline lists pritelivir as an expanded access option. Asahi Kasei describes pritelivir as “the first oral agent” in second-line treatment.

Labeled indication

“HOVILPRI is indicated in immunocompromised adults for the treatment of mucocutaneous lesions caused by herpes simplex virus (HSV) infection that is refractory (with or without documented resistance) to treatment with acyclovir, valacyclovir, or famciclovir” (opens the prescribing information at this quote)

Population described in the FDA approval announcement

“FDA has approved Hovilpri (pritelivir) tablets for adults with weakened immune systems (i.e., immunocompromised patients) who have mucocutaneous lesions caused by herpes simplex virus (HSV) infection and have not responded to other therapies (acyclovir, valacyclovir, or famciclovir).” (opens the source at this quote in a new tab)
“Mucocutaneous lesions occur on skin or mucosal surfaces, such as lips, nostrils, eyes and genitals.” (opens the source at this quote in a new tab)
“Patients with compromised immune systems can have more frequent and serious HSV outbreaks that might not respond well to available treatments because their virus is resistant to the medications or they cannot tolerate side effects.” (opens the source at this quote in a new tab)

Line of therapy: definition of refractory infection in the pivotal trial

“Refractory HSV infection (clinical failure) was defined as no clinical improvement after at least 7 days of standard-of-care nucleoside analogue treatment [acyclovir (ACV), valacyclovir (VACV) or famciclovir (FCV)], with or without laboratory confirmed genotypic/phenotypic resistance for the current HSV outbreak.” (opens the prescribing information at this quote)
“At enrollment, the majority of participants, 71%, had refractory HSV infection and 29% had laboratory confirmed ACV resistance.” (opens the prescribing information at this quote)

“These definitions were developed for use in clinical trials of new therapies, but can provide guidance for clinical practice” (opens the source at this quote in a new tab)

Comparator therapies in PRIOH-1 Part C: prescribing information

“Participants received HOVILPRI (400 mg loading dose on Day 1 followed by 100 mg once daily) or Investigator’s Choice treatment (IV foscarnet, IV/topical cidofovir, or 5% topical imiquimod) for up to 28 days until all mucocutaneous lesions healed, extended up to 42 days total if lesions were improving but not completely healed after 28 days.” (opens the prescribing information at this quote)
“the Investigator’s Choice arm was IV foscarnet (70%), followed by topical 5% imiquimod (14%), IV cidofovir (12%), and topical cidofovir (4%).” (opens the prescribing information at this quote)

Comparator therapies in PRIOH-1 Part C: participants by treatment received

Investigator's choice treatment	Participants (N=50), n (%)
Foscarnet, intravenous	“35 (70)”
Imiquimod, topical	“7 (14)”
Cidofovir, intravenous	“6 (12)”
Cidofovir, topical	“2 (4)”

Use after foscarnet failure or intolerance

“Enrolled participants were immunocompromised and had acyclovir/foscarnet (ACV/FOS) refractory HSV infection or were FOS intolerant (N=35).” (opens the prescribing information at this quote)
“Treatment with HOVILPRI resulted in lesion healing in 40% (95% CI: 23.9, 57.9) of participants during the treatment period up to 28 days and 66% (95% CI: 47.8, 80.9) of participants up to 42 days.” (opens the prescribing information at this quote)

“Patients who are refractory to foscarnet or intolerant currently lack any FDA-approved therapeutic option” (opens the source at this quote in a new tab)

Activity against virus resistant to nucleoside analogues and foscarnet

“Cross resistance is not likely with acyclovir, penciclovir, or foscarnet. Pritelivir retains activity against nucleoside analogue-resistant (e.g., acyclovir) and foscarnet-resistant HSV strains with TK or DNA polymerase substitutions. Substitutions leading to pritelivir resistance do not affect susceptibility to nucleoside analogs and foscarnet.” (opens the prescribing information at this quote)

Disease sites not enrolled in the pivotal trial

“Participants with ocular, CNS, or disseminated HSV disease were not enrolled.” (opens the prescribing information at this quote)

Federal HIV opportunistic infection guideline: preferred and alternative therapy for acyclovir-resistant infection

“Treatment failure due to acyclovir resistance should be suspected if lesions do not begin to resolve within 7–10 days after initiation of anti-HSV therapy.” (opens the source at this quote in a new tab)
“Treatment of acyclovir-resistant HSV should be given in consultation with an infectious disease expert (AIII).” (opens the source at this quote in a new tab)
“IV foscarnet 40 mg/kg every 8–12 hours until clinical response (AI)” (opens the source at this quote in a new tab)
“Topical imiquimod 5% cream three times a week (BIII), or Topical cidofovir 1% gel once daily (BIII), or Topical trifluridine 1% three times a day (BIII), or Topical foscarnet 1% five times a day (BIII), or IV cidofovir 5 mg/kg once weekly for 2 weeks, then every other week (CIII)” (opens the source at this quote in a new tab)
“Based on clinical response; typically 21–28 days or longer” (opens the source at this quote in a new tab)
“Topical formulations of trifluridine, cidofovir, and foscarnet are not commercially available.” (opens the source at this quote in a new tab)
“IV cidofovir is a potential alternative (CIII). Systemic foscarnet and cidofovir are nephrotoxic medications; treatment should be given in consultation with an infectious diseases specialist (AIII) and with frequent laboratory monitoring (see Table 5).” (opens the source at this quote in a new tab)

Federal HIV opportunistic infection guideline: expanded access note and investigational status of pritelivir

“An expanded access program of oral pritelivir is available for immunocompromised people with acyclovir-resistant HSV infection; see the Managing Treatment Failure in Mucocutaneous Disease section for more information.” (opens the source at this quote in a new tab)
“A novel oral agent, the helicase-primase inhibitor pritelivir, is currently being tested in clinical trials for treatment of acyclovir-resistant HSV in immunocompromised people (ClinicalTrials.gov Identifier: NCT03073967).” (opens the source at this quote in a new tab)
“There is an Expanded Access Program available for oral pritelivir in these populations (also see ClinicalTrials.gov Identifier: NCT05844436 for more information).” (opens the source at this quote in a new tab)

Sexually transmitted infections treatment guideline: antiviral-resistant genital herpes

“Such persons should be managed in consultation with an infectious disease specialist, and alternative therapy should be administered.” (opens the source at this quote in a new tab)
“Foscarnet (40–80 mg/kg body weight IV every 8 hours until clinical resolution is attained) is the treatment of choice for acyclovir-resistant genital herpes” (opens the source at this quote in a new tab)
“Intravenous cidofovir 5 mg/kg body weight once weekly might also be effective. Foscarnet and cidofovir are nephrotoxic medications that require intensive laboratory monitoring and infectious disease specialist consultation.” (opens the source at this quote in a new tab)
“Imiquimod 5% applied to the lesion for 8 hours 3 times/week until clinical resolution is an alternative that has been reported to be effective” (opens the source at this quote in a new tab)

Hematopoietic cell transplant guideline: resistant disease

“Foscarnet is the treatment of choice for resistant disease (BI); cidofovir may serve as an alternative (CIII).” (opens the source at this quote in a new tab)

European leukemia guideline: alternative regimens for resistant virus

“If HSV disease is unresponsive to antiviral therapy given at maximum dose, resistance testing should be performed (CIII).” (opens the source at this quote in a new tab)
“Foscarnet 60 mg/kg q12h iv or 40 mg/kg q8h iv for 7-21 d or until complete healing (BIII)” (opens the source at this quote in a new tab)
“Cidofovir 5 mg/kg once a week for 2 weeks, then once every 2 weeks” (opens the source at this quote in a new tab)

Solid organ transplant guideline: acyclovir-resistant infection

“Acyclovir-resistant HSV is less common in SOT patients than in HSCT and can be treated with foscarnet, though other novel therapies are currently under investigation.” (opens the source at this quote in a new tab)

United Kingdom anogenital herpes guideline: drug-resistant herpes and compassionate access to pritelivir

“Systemic therapy with either foscarnet or cidofovir is generally preferred to treat drug resistant herpes in those living with HIV.” (opens the source at this quote in a new tab)
“Pritelivir and amenamevir (helicase primase inhibitors) may also be available through compassionate access.” (opens the source at this quote in a new tab)

European genital herpes guideline: recalcitrant herpes and the pritelivir access program

“Systemic therapy with either foscarnet or cidofovir is generally preferred to treat drug‐resistant herpes in those living with HIV.” (opens the source at this quote in a new tab)
“The efficacy, safety and durability of the therapeutic response of these agents have yet to be determined in prospective controlled trials.” (opens the source at this quote in a new tab)
“Reports of outcomes in the open access pritelivir programme for immunocompromised people living with refractory lesions has shown great promise for this novel helicase primase inhibitor.” (opens the source at this quote in a new tab)

Route of administration against the intravenous standard

“Initiate treatment with a loading dose of 400 mg (four 100 mg tablets) on day 1, followed by a maintenance dose of 100 mg (one tablet) daily by mouth with or without food, until HSV lesions have healed” (opens the prescribing information at this quote)

“As an oral therapy, HOVILPRI provides a non-intravenous treatment option for eligible immunocompromised adult patients with refractory (with or without resistance) HSV infection.” (opens the source at this quote in a new tab)
“When HSV infection does not improve with nucleoside analogue therapy, available treatment options have often required intravenous administration and may present additional treatment-management challenges for patients and healthcare teams.” (opens the source at this quote in a new tab)

Care setting of intravenous foscarnet as described by trial investigators

“Foscarnet IV (SOC): high risk of side effects, requires hospitalization for monitoring and administration” (opens the source at this quote in a new tab)

“the pyrophosphate analogue foscarnet is the main alternative and the only Food and Drug Administration (FDA)–approved agent” (opens the source at this quote in a new tab)
“including electrolyte abnormalities, nephrotoxicity, and the need for hospitalization for intravenous (IV) administration and close monitoring” (opens the source at this quote in a new tab)
“Safe, effective, oral therapies to treat immunocompromised patients with refractory HSV infections with or without resistance remain an unmet medical need.” (opens the source at this quote in a new tab)

Care setting of standard therapy as described by the developer

“Several SoC treatments require intravenous infusions and are poorly tolerated with common side effects including kidney toxicity and electrolyte imbalances with risk of seizures requiring in-patient hospital management.” (opens the source at this quote in a new tab)

Company positioning as second-line therapy

“When symptoms fail to improve and acyclovir resistance is suspected, 2nd line treatment is initiated” (opens the source at this quote in a new tab)
“foscarnet IV injection in hospital setting 1–2 hours per dose,1–3 times per day (daily administration during treatment period [period depends on condition])” (opens the source at this quote in a new tab)
“Once-daily oral administration” (opens the source at this quote in a new tab)
“Pritelivir is a second-line treatment for HSV in immunocompromised patients” (opens the source at this quote in a new tab)
“As the first oral agent in the 2nd-line treatment, targeting a 70% prescription share in the 2nd-line market” (opens the source at this quote in a new tab)

“Market research suggests that prescribing will likely shift significantly toward pritelivir compared to the existing drug foscarnet, which requires intravenous infusion at hospitals, since pritelivir is administered orally once daily. However, market research for new drugs often shows higher prescription intent than actual clinical adoption. Taking this into account, we set the prescription share target conservatively at 70%.” (opens the source at this quote in a new tab)

“Pritelivir is anticipated to address approximately 15,000 immunocompromised patients in the U.S. and is projected to achieve meaningful penetration in the second-line setting, potentially approaching 70%, subject to market conditions.” (opens the source at this quote in a new tab)

Treatment centers and prescribers targeted by the company

“Veloxis Pharmaceuticals, Inc. has an established sales network targeting transplant physicians at transplant centers, cultivated through Envarsus XR.” (opens the source at this quote in a new tab)
“This network already covers more than half of the treatment facilities targeted” (opens the source at this quote in a new tab)

Investigator statements on anticipated use

“Current therapeutic options for hematopoietic cell transplant patients with refractory or resistant herpes simplex viral infection are limited by poor response rates, significant toxicities, and the burden of daily intravenous infusions in a healthcare setting” (opens the source at this quote in a new tab)
“Pritelivir addresses a critical unmet medical need for an oral agent offering statistically superior and clinically meaningful lesion healing with fewer side effects.” (opens the source at this quote in a new tab)

“The subgroup analysis from this Phase 3 trial provides important evidence that pritelivir can achieve meaningful lesion healing in this population, using an oral treatment option.” (opens the source at this quote in a new tab)

“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” (opens the source at this quote in a new tab)

Position of helicase-primase inhibitors: review of refractory and resistant infection after hematopoietic cell transplantation

“Limited data from the Early Access Program, which allows compassionate use, suggest that pritelivir holds promise as a treatment option for HCT recipients with R/R HSV infections.” (opens the source at this quote in a new tab)
“The recommendations outlined in this algorithm are not based on findings from randomized controlled clinical trials but rather on retrospective or observational studies, expert opinion, and clinical experience.” (opens the source at this quote in a new tab)
“The main advantage of HPI over the standard of care is the mechanism of action that does not confer cross-resistance with other anti-HSV agents. However, data on its efficacy, safety, and longer follow-up periods to characterize recurrences are still limited.” (opens the source at this quote in a new tab)

Position of helicase-primase inhibitors: review of drug resistance

“Helicase-primase (UL52/UL5) (HP) inhibitors amenamevir and pritelivir reportedly have less adverse effects. They do not depend on activation by enzymes like TK” (opens the source at this quote in a new tab)
“Long-term safety profile not yet established” (opens the source at this quote in a new tab)

Position of helicase-primase inhibitors: review by authors affiliated with the developer

“Rescue therapies such as foscarnet exhibit limiting toxicity.” (opens the source at this quote in a new tab)
“HPIs represent a significant advance in HSV management. Their safety profile and novel mode of action may provide better viral suppression with a lower risk of resistance, offering hope for better control of the disease.” (opens the source at this quote in a new tab)

Concomitant acid-reducing agents

“Concomitant use of HOVILPRI with certain acid-reducing agents may reduce pritelivir exposure, potentially resulting in reduced therapeutic effect and development of resistance.” (opens the prescribing information at this quote)

Expected commercial availability

“HOVILPRI is expected to be available in the United States before the end of 2026.” (opens the source at this quote in a new tab)