New drug review

Hovilpri

Review section

Field	Value
Drug	Hovilpri (pritelivir)
Indication reviewed	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, in immunocompromised adults
Therapeutic category	Herpes simplex virus helicase-primase inhibitors
Manufacturer	Asahi Kasei Therapeutics, Inc.
Regulatory status	Approved October 9, 2026
Data as of	October 11, 2026
Prepared by	To be completed by the reviewing plan
Review status	Draft for pharmacy and therapeutics committee review

Indications

Table 1. FDA-approved indications

Indications	Hovilpri (pritelivir)
“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”	✓

Definition of refractory infection in the trial supporting the indication

“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)

Disease forms not enrolled and effect of treatment on latent infection

“Participants with ocular, CNS, or disseminated HSV disease were not enrolled.” (opens the prescribing information at this quote)
“Because HSV establishes lifelong latent infection, treatment is not curative.” (opens the prescribing information at this quote)
“Inform patients that HOVILPRI is indicated to heal lesions caused by HSV but is not a cure for HSV infection.” (opens the prescribing information at this quote)

Age range of the indication

“The safety and efficacy of HOVILPRI have not been established in pediatric patients 18 years of age and younger.” (opens the prescribing information at this quote)
“Of the 51 immunocompromised participants treated with HOVILPRI in the Phase 3 PRIOH-1 Part C trial, 20% (10/51) were 65 years and older and 4% (2/51) were 75 years of age and older (range 19-84 years)” (opens the prescribing information at this quote)
“No overall differences in safety or effectiveness were observed between patients 65 years of age and older and younger adult patients.” (opens the prescribing information at this quote)

Pharmacokinetics

Table 2. Pharmacokinetic parameters

Generic Name(s)	Bioavailability	Protein Binding	Metabolism	Excretion	Half-Life
Pritelivir	Absolute bioavailability: “72%”	Plasma protein binding: “97.3%”	“Pritelivir is primarily metabolized by non-enzymatic hydrolysis to its major inactive metabolites, AIC090015 (26.3%)”“AIC090105 (14.4%)”	Percentage of dose excreted in urine: “76.4% (0.6% unchanged)”Percentage of dose excreted in feces: “15.5% (6.0% unchanged)”Major route of elimination: “Non-enzymatic hydrolysis, followed by urinary excretion of the metabolites”	Mean, at 100 mg once daily: “60 h”

How the label reports pharmacokinetic values

“The pharmacokinetic properties of pritelivir following oral administration of HOVILPRI are displayed in Table 2.” (opens the prescribing information at this quote)
“The values are based on a 100 mg once daily dose.” (opens the prescribing information at this quote)
“Food effect after high-fat meal: 150 calories from protein, 250 calories from carbohydrates, and 500-600 calories from fat; a total of 1000 calories with >50% calories from fat.” (opens the prescribing information at this quote)
“Derived from population pharmacokinetic model post-hoc estimates for all participants taking 20-280 mg single or multiple doses.” (opens the prescribing information at this quote)
“Percentages represent the molar ratio of each metabolite to total drug-related material in plasma.” (opens the prescribing information at this quote)
“Dosing in mass balance study: Healthy participants received pritelivir 500 mg (loading dose, Day 1) and 100 mg once daily (Days 2-8), with a [14C]-labeled tracer dose co-administered on Day 8. Values represent recovery of total radioactivity as a percentage of administered dose.” (opens the prescribing information at this quote)
“Pharmacokinetic parameter values based on post-hoc estimates from pritelivir population pharmacokinetic model in immunocompromised participants receiving 100 mg of pritelivir once daily with or without food. Geometric mean (%CV).” (opens the prescribing information at this quote)

Absorption, food effect, distribution, clearance, and steady-state exposure

Parameter	Prescribing information
Time to maximum concentration, mean (range), at 100 mg once daily	“3 h (2.0–4.5 h)”
Food effect on exposure	“AUC ratio fed/fasted: 1.16”
Food effect on maximum concentration	“Cmax ratio fed/fasted: 1.33”
Apparent volume of distribution (Vd/F), geometric mean (%CV)	“64.1 L (37.3%)”
Blood-to-plasma ratio, mean, at 100 mg once daily	“AUC: 1.86”
Apparent clearance (CL/F), geometric mean (%CV)	“1.08 L/h (33.4%)”
Steady-state AUC0-24 (μg•h/mL), geometric mean (%CV)	“91.8 (49.0%)”
Steady-state Cmax (μg/mL), geometric mean (%CV)	“4.62 (50.7%)”
Steady-state Ctrough (μg/mL), geometric mean (%CV)	“3.14 (50.9%)”

Dose proportionality, time to steady state, and accumulation

“Cmax and AUC were dose-proportional after single dose administration (20–480 mg) and multiple dose administration (5–400 mg once daily).” (opens the prescribing information at this quote)
“After multiple dosing of 100 mg once daily, steady state was reached within 8 days.” (opens the prescribing information at this quote)
“When a loading dose of 400 mg pritelivir was administered on Day 1 followed by a maintenance dose of 100 mg once daily, steady-state exposures were reached on Day 2.” (opens the prescribing information at this quote)
“Plasma concentrations at steady state are approximately 5-fold higher than those after single dose administration.” (opens the prescribing information at this quote)

Specific populations

“There were no clinically significant differences in the pharmacokinetics of pritelivir based on age (19 to 84 years), gender, race (including American Indian/Alaska Native, Asian, Black/African American, White, or other), body weight (48 to 176 kg), or underlying immunocompromised condition (including HIV/AIDS, oncology, transplant, or autoimmune/inflammatory disorder).” (opens the prescribing information at this quote)
“In a single-dose pharmacokinetic study, pritelivir exposure (AUC and Cmax) was comparable between participants with mild (eGFR 60–89 mL/min) or moderate (eGFR 30–59 mL/min) renal impairment and those with normal renal function (eGFR ≥90 mL/min).” (opens the prescribing information at this quote)
“Pritelivir exposure (AUC and Cmax) were approximately 1.6- fold higher in participants with severe renal impairment (eGFR 15–29 mL/min, not on hemodialysis) relative to those with normal renal function.” (opens the prescribing information at this quote)
“Pritelivir pharmacokinetics in patients on hemodialysis is unknown.” (opens the prescribing information at this quote)
“In a single-dose pharmacokinetic study, pritelivir exposure (AUC and Cmax) was comparable in participants with moderate hepatic impairment (Child-Pugh Class B) relative to those with normal hepatic function.” (opens the prescribing information at this quote)
“The effect of severe hepatic impairment (Child-Pugh Class C) on pritelivir pharmacokinetics is unknown.” (opens the prescribing information at this quote)

Mechanism of action and antiviral activity

“HOVILPRI is an antiviral drug against HSV-1 and HSV-2 [see Microbiology (12.4)].” (opens the prescribing information at this quote)
“Pritelivir is a HSV helicase-primase inhibitor.” (opens the prescribing information at this quote)
“It is active against both HSV types, HSV-1 and HSV-2, and prevents de novo synthesis of virus deoxyribonucleic acid (DNA) through inhibition of the viral helicase-primase complex.” (opens the prescribing information at this quote)
“Kinetic analysis of the enzyme complex pUL5-pUL52-6xHis revealed the IC50 value of 30 nM.” (opens the prescribing information at this quote)
“Pritelivir exhibits an apparent 50% effective concentration (EC50 value) between 0.01 μM and 0.07 μM in cell culture infected with HSV-1 or HSV-2 (laboratory strains and clinical isolates), depending on cell type, virus strain/isolate, and method used.” (opens the prescribing information at this quote)
“The median EC50 values of pritelivir were 26 nM (average 26 nM, range 10-45 nM, n=27) and 24 nM (average 30 nM, range 7-70 nM, n=32) against HSV-1 and HSV-2 clinical isolates, respectively.” (opens the prescribing information at this quote)

Exposure-response and cardiac electrophysiology

“No exposure-response relationship was identified between steady-state plasma pritelivir exposures at 100 mg once daily and the occurrence of all lesions healed by Day 28.” (opens the prescribing information at this quote)
“At 4 times the recommended maintenance pritelivir dose, clinically significant QTc interval prolongation was not observed.” (opens the prescribing information at this quote)

Drug interactions

Table 3. Major drug interactions

Generic Name(s)	Interaction	Mechanism
Pritelivir	Proton pump inhibitors (esomeprazole, rabeprazole, omeprazole, lansoprazole, pantoprazole)	“Elevation of gastric pH may decrease the systemic bioavailability of HOVILPRI”“which may reduce its effectiveness or cause drug resistance to HOVILPRI”“Avoid concomitant use of esomeprazole or rabeprazole with HOVILPRI. Avoid concomitant use of omeprazole or lansoprazole at daily doses above 20 mg with HOVILPRI. Avoid concomitant use of pantoprazole at daily doses above 40 mg with HOVILPRI”“Concomitant use of omeprazole, lansoprazole, or pantoprazole below the doses listed above is acceptable, as these lower doses do not reduce pritelivir exposure to a clinically relevant extent.”“Co-administration of a single oral dose of 100 mg pritelivir (on Day 1) with esomeprazole 40 mg once daily (from Day -3 to Day 1; 4 days total) decreased Cmax by approximately 76% and AUC by approximately 59% compared to pritelivir administered alone”“In the Phase 3 trial (PRIOH-1, Parts C-F), pritelivir exposures were evaluated for participants who received concomitant omeprazole or lansoprazole (≤20 mg daily), pantoprazole (≤40 mg daily), or an H2-receptor antagonist (with pritelivir administered at least 2 hours before or 12 hours after the H2-receptor antagonist).”“Pritelivir exposures in participants receiving these acid-reducing agents were not clinically meaningfully different from those in participants who did not receive any acid-reducing agents”
Pritelivir	H2-receptor antagonists	“Elevation of gastric pH may decrease the systemic bioavailability of HOVILPRI”“which may reduce its effectiveness or cause drug resistance to HOVILPRI”“Take HOVILPRI at least 2 hours before or 12 hours after H2- receptor antagonist intake”“In the Phase 3 trial (PRIOH-1, Parts C-F), pritelivir exposures were evaluated for participants who received concomitant omeprazole or lansoprazole (≤20 mg daily), pantoprazole (≤40 mg daily), or an H2-receptor antagonist (with pritelivir administered at least 2 hours before or 12 hours after the H2-receptor antagonist).”“Pritelivir exposures in participants receiving these acid-reducing agents were not clinically meaningfully different from those in participants who did not receive any acid-reducing agents”
Pritelivir	Antacids	“Elevation of gastric pH may decrease the systemic bioavailability of HOVILPRI”“which may reduce its effectiveness or cause drug resistance to HOVILPRI”“Take HOVILPRI at least 2 hours before or 2 hours after antacid intake”
Pritelivir	BCRP substrates (rosuvastatin studied)	“Pritelivir is a breast cancer resistance protein (BCRP) inhibitor. Co-administration of HOVILPRI with a BCRP substrate may increase the plasma concentrations of the BCRP substrate”“which may increase the risk of adverse reactions. Refer to the prescribing information for co-administered drugs for additional information.”“Co-administration of multiple pritelivir doses (400 mg on Day 1 followed by 100 mg once daily on Day 2 and Day 3) with a single 20 mg oral dose of rosuvastatin (on Day 3) resulted in a 1.7-fold increase in Cmax and a 1.4-fold increase in AUC of rosuvastatin compared to rosuvastatin administered alone”
Pritelivir	CYP2B6, CYP2C8, CYP2C9, CYP3A4, and OATP2B1 substrates (clinical studies)	“No clinically significant changes in substrate exposures were observed in clinical drug-drug interaction trials when pritelivir was co-administered with the cytochrome P450 (CYP)2B6 substrate bupropion, the CYP2C8 substrate repaglinide, the CYP2C9”“substrate flurbiprofen, the CYP3A4 substrate midazolam, and the organic anion transporting polypeptide (OATP)2B1 substrate celiprolol.”
Pritelivir	CYP enzyme inhibitors or inducers, and P-gp or BCRP inhibitors (in vitro)	“As pritelivir is primarily metabolized by non-enzymatic hydrolysis, leading to the formation of AIC090015 and AIC090105, clinically relevant drug-drug interactions with pritelivir as a CYP enzyme substrate are not expected.”“Pritelivir is a substrate of both P-glycoprotein (P-gp) and BCRP efflux transporters in vitro, but is not a substrate of OATP1B1, OATP1B3, OATP2B1, organic cation transporter (OCT)1, or organic anion transporter (OAT)1.”“Because pritelivir has a high absolute oral bioavailability of 72%, co-administration of P- gp or BCRP inhibitors is not expected to impact the oral absorption of HOVILPRI to a clinically relevant extent.”
Pritelivir	CYP450 enzyme substrates and transporter substrates (in vitro)	“Pritelivir does not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP2E1, or CYP3A4/5 at clinically relevant exposures.”“Pritelivir does not cause clinically relevant induction of CYP1A2, CYP2C9, or CYP2C19.”“Pritelivir does not cause time-dependent inhibition of any CYP enzymes.”“Pritelivir does not inhibit P-gp, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, multidrug and toxin extrusion protein (MATE)1, or MATE2-K at clinically relevant exposures.”“The major circulating metabolites of pritelivir, AIC090015 and AIC090105, are not expected to inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 to a clinically relevant extent.”“No clinically significant differences in the pharmacokinetics of OAT substrates are predicted when co- administered with HOVILPRI 100 mg once daily.”

Abbreviations: AUC=area under the concentration-time curve; BCRP=breast cancer resistance protein; Cmax=maximum concentration; CYP=cytochrome P450; H2=histamine type 2; MATE=multidrug and toxin extrusion protein; OAT=organic anion transporter; OATP=organic anion transporting polypeptide; OCT=organic cation transporter; P-gp=P-glycoprotein

Warning on 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)
“Avoid concomitant use with certain proton pump inhibitors, and stagger concomitant use with H2-receptor antagonists and antacids” (opens the prescribing information at this quote)

Geometric mean ratio (90% CI) of exposure with and without the co-administered drug in the interaction studies

Analyte	Co-administered drug and regimen	Pritelivir regimen	N	AUC0-inf	AUC0-last	Cmax
Pritelivir	Esomeprazole 40 mg once daily	“100 mg single dose”	“15”	“0.41 (0.36, 0.48)”	“0.41 (0.35, 0.47)”	“0.24 (0.20-0.30)”
Rosuvastatin	Rosuvastatin 20 mg single dose	“100 mg once daily”	“16”	“1.37 (1.27, 1.48)”	“1.41 (1.28, 1.56)”	“1.67 (1.45, 1.92)”

Counseling on disclosure of other medicines

“Inform patients that HOVILPRI may interact with some drugs; therefore, advise patients to report the use of any other medications to their healthcare provider” (opens the prescribing information at this quote)

Adverse drug events

Table 4. Adverse drug events reported in more than 5% of participants receiving Hovilpri in PRIOH-1 Part C, with treatment for up to 42 days

Adverse Event	Hovilpri (N = 51), %	Investigator's Choice (N = 50), %
Headache (all grades)	“6%”	“4%”

Adverse reactions as the label states them

“The most common adverse reaction (incidence >5%) was headache.” (opens the prescribing information at this quote)
“The adverse reaction (all grades) occurring in more than 5% of participants receiving HOVILPRI was headache, which occurred in 6% and 4% of the HOVILPRI and Investigator’s choice participants, respectively.” (opens the prescribing information at this quote)
“Adverse reactions were reported in 22% of HOVILPRI-treated participants, compared with 54% of participants in the Investigator’s Choice treatment arm.” (opens the prescribing information at this quote)
“Discontinuations due to adverse drug reactions occurred in 2% and 20% of participants, respectively.” (opens the prescribing information at this quote)

Overall incidence of adverse reactions, discontinuations, and hepatic laboratory abnormalities in PRIOH-1 Part C by treatment arm

Event	Hovilpri (N = 51)	Investigator's Choice (N = 50)
Any adverse reaction	“22%”	“54%”
Discontinuation due to adverse drug reactions	“2%”	“20%”
ALT elevation of 2.5 times the upper limit of normal or more	“4/51 (8%)”	“1/50 (2%)”
AST elevation of 2.5 times the upper limit of normal or more	“3/51 (6%)”	“2/50 (4%)”

Hepatic laboratory abnormalities

“Hepatic laboratory abnormalities were observed in both treatment groups in PRIOH-1, Part C.” (opens the prescribing information at this quote)
“ALT elevations ≥2.5 × upper limit of normal (ULN) were reported in 4/51 (8%) participants receiving HOVILPRI and 1/50 (2%) receiving Investigator’s Choice, while AST elevations ≥2.5 × ULN were reported in 3/51 (6%) and 2/50 (4%) participants, respectively.” (opens the prescribing information at this quote)
“One participant discontinued HOVILPRI due to elevated liver enzymes.” (opens the prescribing information at this quote)

Trial and treatment duration in the safety evaluation

“The safety of HOVILPRI was evaluated in 206 adults treated with HOVILPRI and an additional 100 healthy adult participants exposed to HOVILPRI in clinical trials.” (opens the prescribing information at this quote)
“The safety of HOVILPRI was evaluated in a Phase 3, randomized, open-label, comparator-controlled trial, PRIOH-1 (Part C), in immunocompromised participants with mucocutaneous (mucosal and/or cutaneous lesions) HSV infection that was refractory (with or without documented resistance) to treatment with acyclovir, valacyclovir, or famciclovir” (opens the prescribing information at this quote)
“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 lesions healed, extended up to 42 days if lesions were improving.” (opens the prescribing information at this quote)
“A total of 101 participants were randomized 1:1 and treated with either HOVILPRI or the Investigator’s Choice.” (opens the prescribing information at this quote)
“Across the 51 participants treated with HOVILPRI, the mean duration of treatment was 27.1 days (range 6–43).” (opens the prescribing information at this quote)
“Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.” (opens the prescribing information at this quote)

Safety in PRIOH-1 Parts D and F

“The safety of HOVILPRI was also evaluated in a non-randomized, open-label, multicenter, single-arm Phase 3 trial, PRIOH-1 (Parts D and F) in immunocompromised adults with acyclovir/foscarnet (ACV/FOS) refractory HSV infection or who were FOS intolerant (N=35).” (opens the prescribing information at this quote)
“The safety and tolerability profile observed in these” (opens the prescribing information at this quote)
“populations was consistent with that observed in Part C, with no new or unexpected adverse drug reactions identified.” (opens the prescribing information at this quote)

Contraindications

“None.” (opens the prescribing information at this quote)

Pregnancy and lactation

“There are no available data on HOVILPRI use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.” (opens the prescribing information at this quote)
“In animal reproduction studies, no” (opens the prescribing information at this quote)
“adverse developmental effects were observed when pritelivir was administered to rats and rabbits at exposures (AUC) approximately 16- (rats) and 2- (rabbits) times the systemic pritelivir exposure in humans at the therapeutic dose of 100 mg” (opens the prescribing information at this quote)
“The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.” (opens the prescribing information at this quote)
“In both species, developmental toxicities were only observed at maternally toxic doses, ≥200 mg/kg/day in the rat, and ≥40 mg/kg/day in the rabbit, resulting in low birth weights in both species, skeletal variations in the rat and fetal loss in rabbits at doses ≥60 mg/kg/day.” (opens the prescribing information at this quote)
“There are no data on the presence of pritelivir or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production.” (opens the prescribing information at this quote)
“The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for HOVILPRI and any potential adverse effects on the breastfed infant from HOVILPRI or from the underlying maternal condition.” (opens the prescribing information at this quote)

Fertility findings in humans and animals

“There are no data on the effect of pritelivir on human fertility.” (opens the prescribing information at this quote)
“A fertility study of pritelivir in rats (50, 150 and 500 mg/kg/day) showed adverse effects on male fertility at 500 mg/kg/day.” (opens the prescribing information at this quote)
“Male rats dosed at 500 mg/kg/day exhibited direct effects on epididymal sperm counts, sperm motility and morphology and a minor increase in severity in lumen detritus in the epididymis.” (opens the prescribing information at this quote)
“At 150 mg/kg/day, male rats exhibited slight reduction of epididymal sperm counts as well as minor changes in sperm morphology.” (opens the prescribing information at this quote)
“The effects were confirmed to be reversible after 6 weeks of discontinuing pritelivir with no lasting adverse effects on male reproduction.” (opens the prescribing information at this quote)
“No effects on fertility or the offspring occurred at 50 mg/kg/day approximately 6-times the human exposure (AUC) at the therapeutic dose of 100 mg.” (opens the prescribing information at this quote)
“Sexually mature male monkeys dosed at 1,000 mg/kg/day for 39 weeks had no findings in the reproductive organs or semen” (opens the prescribing information at this quote)

Nonclinical toxicology: carcinogenesis, mutagenesis, and ocular findings

“Carcinogenicity studies with pritelivir are ongoing.” (opens the prescribing information at this quote)
“Pritelivir free base and pritelivir mesylate monohydrate were not mutagenic in in vitro and in vivo genotoxicity assays which included bacterial mutation assays in S. typhimurium, micronucleus tests with cultured mammalian cells, and in the rodent micronucleus assay.” (opens the prescribing information at this quote)
“In a 26-week oral toxicity study in rats at 10, 50, 250 mg/kg/day, early stages of lenticular opacity (cataracts) and vitreous floaters in the eye were observed at 250 mg/kg/day.” (opens the prescribing information at this quote)
“In a 13-week mouse toxicity study at 100, 500, 1,500 mg/kg/day, lenticular opacity and compound depositions were noted at ≥500 mg/kg/day.” (opens the prescribing information at this quote)
“No ocular findings occurred in the rat and mouse at systemic exposures (AUC) approximately 28- (rats) and 14- (mice) times the human exposure at the therapeutic dose of 100 mg.” (opens the prescribing information at this quote)
“Further, no ocular findings were apparent in the monkey with up to 39 weeks of treatment at 1,000 mg/kg/day.” (opens the prescribing information at this quote)

Overdosage

“There is no known specific antidote for HOVILPRI.” (opens the prescribing information at this quote)
“In the event of an overdose, patients should be monitored for adverse reactions and managed with supportive care, as appropriate.” (opens the prescribing information at this quote)
“Due to the high plasma protein binding of pritelivir, hemoperfusion or dialysis is unlikely to significantly reduce systemic exposure of pritelivir.” (opens the prescribing information at this quote)

Dosing and administration

Table 5. Usual dosing regimens

Generic Name	Usual Adult Dose	Usual Pediatric Dose	Availability
Pritelivir	“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”	“The safety and efficacy of HOVILPRI have not been established in pediatric patients 18 years of age and younger.”	“Tablets: 100 mg of pritelivir.”“HOVILPRI film-coated tablets are white to off-white, round, biconvex and contain 100 mg pritelivir.”“HOVILPRI is available in cartons of 16 or 32 film-coated tablets.”“NDC 68992-100-32”“NDC 68992-100-16”

See the current prescribing information for full details.

Co-administration with acid-reducing agents

“While taking HOVILPRI, avoid concomitant use of the following proton pump inhibitors” (opens the prescribing information at this quote)
“Esomeprazole or rabeprazole” (opens the prescribing information at this quote)
“Omeprazole or lansoprazole at daily doses above 20 mg” (opens the prescribing information at this quote)
“Pantoprazole at daily doses above 40 mg” (opens the prescribing information at this quote)
“Take HOVILPRI 2 hours before or 12 hours after taking a H2-receptor antagonist” (opens the prescribing information at this quote)
“Separate any dosing of antacids from HOVILPRI dosing by 2 hours” (opens the prescribing information at this quote)

Missed dose

“If a dose of HOVILPRI is missed, take it as soon as it is remembered. If it is not taken until the scheduled dosing time on the next day, take two tablets at that time.” (opens the prescribing information at this quote)
“Inform patients that it is important not to miss or skip doses and to take HOVILPRI for the duration that is recommended by the healthcare provider.” (opens the prescribing information at this quote)

Dosage in renal and hepatic impairment

“No dose adjustment is recommended for patients with mild, moderate, or severe renal impairment.” (opens the prescribing information at this quote)
“The pharmacokinetics and safety of pritelivir in patients requiring hemodialysis have not been evaluated” (opens the prescribing information at this quote)
“No dose adjustment is recommended for patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment.” (opens the prescribing information at this quote)
“The pharmacokinetics and safety of pritelivir in patients with severe hepatic impairment (Child-Pugh Class C) have not been evaluated” (opens the prescribing information at this quote)

Treatment duration studied in PRIOH-1 Part C

“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)
“Across the 51 participants treated with HOVILPRI, the mean duration of treatment was 27.1 days (range 6–43).” (opens the prescribing information at this quote)
“33 % of participant in the HOVILPRI arm extended treatment up to 42 days, whose lesions were improving by Day 28.” (opens the prescribing information at this quote)

Tablet description and composition

“The tablets are embossed with ‘AIC’ on one side and with ‘1’ on the other side.” (opens the prescribing information at this quote)
“Each tablet contains 100 mg of pritelivir (equivalent to 123.9 mg of pritelivir mesylate) and is available as immediate release tablets for oral administration.” (opens the prescribing information at this quote)
“The tablet core contains standard excipients: colloidal silica dioxide, croscarmellose sodium, magnesium stearate, mannitol, and microcrystalline cellulose, as well as the film-coat (hydroxy propyl methyl cellulose and polyethylene glycol) and the colorant/opacifier calcium diphosphate.” (opens the prescribing information at this quote)

Packages and national drug codes

Package	NDC	Contents
Carton of 32 tablets	“NDC 68992-100-32”	“Each carton contains two blister wallets. Each blister wallet contains 16 film-coated tablets, for a total of 32 film-coated tablets per carton.”
Carton of 16 tablets	“NDC 68992-100-16”	“Each carton contains one blister wallet containing 16 film-coated tablets.”

Storage

“Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].” (opens the prescribing information at this quote)
“Keep HOVILPRI and all medicines out of the reach of children.” (opens the prescribing information at this quote)

Effectiveness

Table 6. Comparative clinical trials

Study and Drug Regimen	Study Design and Demographics	Study Size and Duration	End Points	Results
PRIOH-1 Part C (protocol AIC316-03-II-01; NCT03073967): “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.”Treatments received in the comparator arm: “Investigator’s Choice arm was IV foscarnet (70%), followed by topical 5% imiquimod (14%), IV cidofovir (12%), and topical cidofovir (4%).”	“The efficacy of HOVILPRI was evaluated in a randomized, open-label, comparator-controlled, superiority trial (PRIOH-1 Phase 3 Trial, Part C; NCT 03073967) in immunocompromised participants with mucocutaneous (mucosal and/or cutaneous lesions) HSV infection that was refractory (with or without documented resistance) to treatment with acyclovir, valacyclovir, or famciclovir.”“Participants with ocular, CNS, or disseminated HSV disease were not enrolled.”“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.”“The mean age of participants was 53 years (range 19-84 years), 53% were male. Race and ethnicity were as follows: 49% White, 23% Black/African American, 16% American Indian/Alaska native, 10% other, and 3% Asian; 26 % were of Hispanic/Latino ethnicity.”“At enrollment, the majority of participants, 71%, had refractory HSV infection and 29% had laboratory confirmed ACV resistance.”“Participants represented a wide range of immunosuppressive clinical conditions, including one or more of the following underlying conditions: hematologic malignancy/disorder (47%), hematopoietic stem-cell transplantation (40%), HIV infection (38%), autoimmune/inflammatory diseases (29%), non-hematologic malignancies (26%) or solid-organ transplantation (4%).”	“A total of 101 participants (≥18 years) were randomized 1:1 and treated with HOVILPRI (N = 51) or Investigator’s Choice (N =50).”“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”“Across the 51 participants treated with HOVILPRI, the mean duration of treatment was 27.1 days (range 6–43).”“33 % of participant in the HOVILPRI arm extended treatment up to 42 days, whose lesions were improving by Day 28.”	Primary: “The primary efficacy endpoint was the proportion of participants with all lesions healed with complete epithelization, as assessed by the Investigator, (response rate) during the treatment period up to 28 days.”“Response rate defined as all mucocutaneous HSV lesions healed by complete epithelization within the treatment period and no appearance of new lesions post-end of treatment, as assessed by the Investigator.”Secondary: “The secondary endpoint was the response rate up to 42 days.”	Response rate up to Day 28, Hovilpri, n/N (%): “32/51 (63%)”Response rate up to Day 28, Investigator's Choice, n/N (%): “17/50 (34%)”Adjusted treatment difference (95% CI): “28.4 (9.6, 47.3)”p-value: “0.0047”“n=number of participants with healed lesions within the respective treatment arm; N=number of participants in the respective arm”“Full Analysis Set.”“The stratified Cochran-Mantel-Haenszel test was used to compare treatment groups, adjusting for protocol versions that reflected change in the control arm design.”“Confidence Intervals are based on the stratified Sato method and the p-value from the stratified CMH test.”Response rate up to 42 days: “The observed response rates were 82% treated with HOVILPRI vs. 42% with Investigator’s Choice, with an adjusted treatment difference of 40% (95% CI: 22.7, 57.7).”
PRIOH-1 Parts D and F (protocol AIC316-03-II-01; NCT03073967): “HOVILPRI (400 mg loading dose on Day 1 followed by 100 mg once daily)”	“The efficacy of HOVILPRI was further evaluated in Parts D and F of Trial PRIOH-1, which had a non-randomized, open-label, single-arm design to assess the efficacy and safety of HOVILPRI (400 mg loading dose on Day 1 followed by 100 mg once daily).”“Enrolled participants were immunocompromised and had acyclovir/foscarnet (ACV/FOS) refractory HSV infection or were FOS intolerant (N=35).”“Underlying immunosuppressive conditions included hematologic malignancy/disorder, hematopoietic stem-cell transplantation, non-hematologic malignancies, HIV infection, autoimmune/inflammatory diseases and solid-organ transplantation.”	“N=35”“during the treatment period up to 28 days”“of participants up to 42 days”	Not reported	“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.”

Abbreviations: ACV=acyclovir; CI=confidence interval; CMH=Cochran-Mantel-Haenszel; CNS=central nervous system; FCV=famciclovir; FOS=foscarnet; HIV=human immunodeficiency virus; HSV=herpes simplex virus; IV=intravenous; VACV=valacyclovir

Numbering of the primary efficacy table in the prescribing information

“The primary efficacy result from PRIOH-1 is displayed in Table 8.” (opens the prescribing information at this quote)
“Table 6: Primary Efficacy Result in PRIOH-1, Part C” (opens the prescribing information at this quote)

Viral resistance in clinical trials

“In the PRIOH-1 Phase 3 trial (NCT 03073967) in immunocompromised participants, viral sequence analysis was performed on samples obtained from pritelivir-treated participants who did not heal on pritelivir treatment and for whom on-treatment samples were available for analysis.” (opens the prescribing information at this quote)
“Paired baseline and on-treatment/end-of-treatment sequences were obtained for 8.3% (4/48) of pritelivir-treated participants who experienced treatment failure (lesions not healed by Day 28).” (opens the prescribing information at this quote)
“The pUL5 K356N (>1,000-fold reduction in susceptibility in cell culture) substitution was detected in 1 participant infected with HSV-1.” (opens the prescribing information at this quote)
“The pUL5 K355R (50-fold reduction, 2 participants) and pUL5 N341K, pUL5 G351R (distinct viral subpopulations, 33-fold reduction, 1 participant) substitutions were detected in participants infected with HSV-2.” (opens the prescribing information at this quote)
“In the PRIOH-1 Phase 2 trial (NCT 03073967), the pUL5 K355T (12-fold reduction, 1 participant) substitution was detected in a participant infected with HSV-2.” (opens the prescribing information at this quote)
“In another study, the HSV-1 pUL5 N342K (38-fold reduction) + G352C (fold reduction not available) + K356R (fold reduction not available) + pUL52 A899T (100-fold reduction) substitutions were detected in one participant one week after pritelivir discontinuation.” (opens the prescribing information at this quote)

Resistance-associated amino acid substitutions selected in cell culture

Virus	Protein	Substitutions
HSV-1	“pUL5 helicase”	“N342K, G352R, G352C, G352V, G352N, M355T, K356N, K356T, K356Q, K356R, K356E”
HSV-1	“pUL52 primase”	“A899T”
HSV-2	“pUL5 helicase”	“N341K, G351R, M354T, K355N, K355T, K355R”
HSV-2	“pUL52 primase”	“A906T”

Cross-resistance with nucleoside analogues and foscarnet

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

Protocol primary outcome measure in the ClinicalTrials.gov record

Field	Registry value
Outcome measure	“Efficacy measured by cure rate”
Measure description	“Number of subjects cured (all lesions healed as assessed by the Investigator) during the treatment period of up to 28 days relative to the total number of subjects treated with trial medication in the respective treatment group.”
Time frame	“Up to a maximum of 28 days”

Endpoints of Parts D and F in the EU Clinical Trials Register record, which the prescribing information does not define

“Endpoints will be evaluated separately in Part C, Part D and Part F.” (opens the source at this quote in a new tab)
“Cure rate: number of subjects cured (all lesions healed as assessed by the Investigator) during the treatment period of up to 28 days relative to the total number of subjects treated with trial medication in the respective treatment group.” (opens the source at this quote in a new tab)

Registered secondary outcome measures for which the prescribing information reports no value

Outcome measure	Measure description	Time frame
Time to lesion healing	“Time to lesion healing, defined as complete epithelization of the mucocutaneous HSV lesion(s) within the treatment period and no appearance of new lesions, as assessed by the Investigator.”	“Up to a maximum of 42 days”
Recurrence rate at 2 months	“Recurrence rate at 2 months following PoTV assessed by telephone, defined as number of subjects with a recurrence as assessed by the Investigator following 2/3 months after PoTV relative to the total number of subjects assessed for recurrence at the respective telephone call per treatment.”	“At 2 months following post treatment visit, from randomization up to a maximum of 108 days”
Recurrence rate at 3 months	“Recurrence rate at 3 months following PoTV assessed by telephone, defined as number of subjects with a recurrence as assessed by the Investigator following 2/3 months after PoTV relative to the total number of subjects assessed for recurrence at the respective telephone call per treatment.”	“At 3 months following post treatment visit, from randomization up to a maximum of 139 days”
Pain rate	“Number of days with pain at lesion site relative to the total number of days with analyzable pain data through daily subject self-reporting”	“Up to a maximum of 42 days”
Time to pain cessation at site of lesion	“Starting at first dose of trial medication until pain is no longer reported by the subject (date and time)”	“Up to a maximum of 42 days”
Average pain score	“Using a single-dimensional scale assessing pain intensity through daily subject self-reporting”	“Up to a maximum of 42 days”
Clinical shedding rate	“Number of HSV positive swabs per subject relative to the total number of swabs collected per subject from lesion swabs taken from HSV lesion(s)”	“From date of randomization until the date of first documented healing, assessed up to a maximum of 42 days”
Time to cessation of shedding	“Number of days until swabs taken are negative”	“Up to a maximum of 42 days”