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Hovilpri (pritelivir)

Refractory mucocutaneous herpes simplex virus infection in immunocompromised adults

Also known as AIC316
Last updated
239 sources

Product information and disease descriptionPlace of product in therapyApproaches to treatment

Expected outcomes of therapy

22 evidence topics · 9 sources

Lesion healing as the treatment goal

“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. Because HSV establishes lifelong latent infection, treatment is not curative.” (opens the prescribing information at this quote)

“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.” (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)

Proportion healed by day 28: prescribing information
Primary endpointHovilpri, n/N (%)Investigator's choice, n/N (%)Adjusted treatment difference (95% CI)P value
Response rate: proportion of participants with lesions healed up to day 28“32/51 (63%)”“17/50 (34%)”“28.4 (9.6, 47.3)”“0.0047”
Proportion healed by day 28: FDA approval announcement

“By 28 days, all lesions were healed in 63% of patients receiving Hovilpri, compared with 34% of patients receiving one of the other medications.” (opens the source at this quote in a new tab)

Proportion healed by day 42: prescribing information

“The secondary endpoint was the 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).” (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)

Proportion healed by day 28 and day 42: congress presentation

“Pritelivir achieved a statistically significant higher rate of complete lesion healing (62.7%) vs ICT (34%), up to 28 days of treatment; adjusted treatment difference 28.4% (95% CI, 9.6-47.3); p=0.0047” (opens the source at this quote in a new tab)

“82.4% of pritelivir treated patients achieved complete lesion healing vs 42% with ICT; adjusted treatment difference 40.2% (95% CI, 22.7-57.7); p<0.0001” (opens the source at this quote in a new tab)

Proportion healed after foscarnet failure or intolerance

“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)

Time to lesion healing in Part C

No evidence found.

Time to lesion healing: phase 2 Parts A and B

“The primary end point, time to lesion healing up to a maximum of 28 days of treatment as assessed by IPR, demonstrated a median time to healing of 26.0 days (95% CI, 13.0–31.0) in the pritelivir arm vs NE (95% CI, 20.0–NE) in the foscarnet arm (NE as <50% were assessed as healed).” (opens the source at this quote in a new tab)

“Based on investigator assessment, the median time to lesion healing was 19.0 days (95% CI, 15.0–25.0) in the pritelivir arm and 21.0 days (95% CI, 11.0–NE) in the foscarnet arm.” (opens the source at this quote in a new tab)

“Overall, 93.3% of participants in the pritelivir arm and 57.1% in the foscarnet arm achieved lesion healing, corresponding to a treatment difference of 36.2% (95% CI, −10.1% to 74.1%; P = .077)” (opens the source at this quote in a new tab)

“Median time to lesion healing assessed by IPR within 28 days in Part B was 19.0 days” (opens the source at this quote in a new tab)

Time to undetectable HSV DNA in lesions

“MEDIAN TIME TO UNDETECTABLE HSV DNA IN THE MUCOCUTANEOUS LESIONS WAS SHORTER ON PRITELIVIR: 9 DAYS VS ICT 21 DAYS” (opens the source at this quote in a new tab)

“Hazard ratio 1.76 (HR >1 favors pritelivir); 95% CI, 0.98-3.16; p = 0.0581” (opens the source at this quote in a new tab)

“Analysis performed on subgroup of patients who had a positive HSV DNA PCR result at baseline. Patients who had positive HSV DNA PCR result at the post-treatment visit were censored at that visit.” (opens the source at this quote in a new tab)

“HSV DNA limit of detection ≥150 copies/mL.” (opens the source at this quote in a new tab)

“Pritelivir treatment significantly reduced viral replication and viral burden, shortening the median time to undetectable HSV in lesions to 9 days compared with 21 days with ICT (p = 0.0581)” (opens the source at this quote in a new tab)

HSV DNA detection rate and cessation of detection in Part C
MeasurePritelivirInvestigator's choiceComparison
Mean HSV DNA detection rate in lesion swabs“26,4%”“54,1%”“Risk Ratio = 0.37 95% CI, 0.23-0.59 p<0.0001”
Participants with cessation of HSV DNA detection (post hoc analysis), %“73.7%”“48.7%”“Difference: 25.0% 95% CI, 2.7-45.5 p=0.025”
Participants with cessation of HSV DNA detection (post hoc analysis), count“n = 28/38”“n = 19/39”“Patients with no detectable HSV DNA at baseline have been excluded from the analysis.”

“Observed treatment effects with pritelivir align with efficient control of viral replication and reduction in viral burden” (opens the source at this quote in a new tab)

HSV DNA detection in the phase 2 parts

“HSV DNA obtained from lesion swabs collected during study visits in the treatment period and at the end-of-treatment visit was detected less often in the pritelivir arm (34.8%) than the foscarnet arm (50.0%), but the difference was not significant” (opens the source at this quote in a new tab)

Pain outcomes

No evidence found.

Recurrence after treatment in Part C

No evidence found.

Recurrence after treatment: phase 2 Parts A and B

“Within the 4-week follow-up period, lesion recurrence was observed in 3 of 14 pritelivir-treated participants and in none of the 4 participants who achieved lesion healing in the foscarnet arm” (opens the source at this quote in a new tab)

“One of 5 healed participants experienced a recurrence.” (opens the source at this quote in a new tab)

“As healing rates were higher with pritelivir, more pritelivir-treated participants contributed to the recurrence analysis, introducing potential bias and limiting interpretability.” (opens the source at this quote in a new tab)

Emergence of resistance during treatment: prescribing information

“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. 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)

Emergence of resistance during treatment: congress presentation

“Resistance investigated in treatment failures with detectable HSV DNA at post-treatment visit” (opens the source at this quote in a new tab)

“One person with pritelivir resistance in an HCT patient with HSV-2” (opens the source at this quote in a new tab)

“Only 1 participant on pritelivir with failure (lesions improving but not completely healed) with detectable HSV DNA at post-treatment visit (after 42 days of treatment)” (opens the source at this quote in a new tab)

“Two pritelivir resistance-associated substitutions (UL5 N341K and G351R) detected” (opens the source at this quote in a new tab)

“Both substitutions were not present at baseline and emerged on treatment day 36” (opens the source at this quote in a new tab)

“Foscarnet-resistant mutations detected in a PLHIV with HSV-2” (opens the source at this quote in a new tab)

Emergence of resistance during treatment: phase 2 parts

“Resistance to foscarnet was observed in 1 of 7 foscarnet-treated participants (E798K substitution in the HSV-2 pUL30 polymerase), and resistance to pritelivir in 1 of 15 pritelivir-treated participants (K355T substitution in the pUL5 helicase).” (opens the source at this quote in a new tab)

Treatment duration: prescribing information

“Recommended dose is 400 mg on the first day, followed by 100 mg once daily with or without food, until HSV lesions have healed.” (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)

“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)

“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)

Treatment duration: days of exposure by treatment in Part C
Extent of exposure, daysPritelivir (N=51)Foscarnet, intravenous (N=35)Cidofovir, intravenous (N=6)Cidofovir, topical (N=2)Imiquimod, topical (N=7)
Mean (SD)“27.1 (10.88)”“18.2 (11.79)”“14.7 (10.39)”“34.5 (10.61)”“34.7 (12.13)”
Median“27.0”“16.0”“13.0”“34.5”“43.0”
Minimum, maximum“6, 43”“1, 43”“7, 35”“27, 42”“17, 45”
Completion and discontinuation of treatment in Part C

“Completed Pritelivir N=48 (94.1%)” (opens the source at this quote in a new tab)

“Completed Investigator’s Choice N=27 (54%)” (opens the source at this quote in a new tab)

“Withdrawn N=3 (5.9%) (Not completed treatment) Adverse events: n=3 (5.9%)” (opens the source at this quote in a new tab)

“Withdrawn N=23 (46%) (Not completed treatment) Adverse event: n=1 (2%) Death: n=3 (6%) FOS intolerance: n=9 (18%) Failure/new lesions: n=5 (10%) Physician decision/subject withdrawal/other: n=5 (10%)” (opens the source at this quote in a new tab)

Adverse reactions and discontinuation because of adverse reactions: prescribing information

“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. Discontinuations due to adverse drug reactions occurred in 2% and 20% of participants, respectively.” (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. One participant discontinued HOVILPRI due to elevated liver enzymes.” (opens the prescribing information at this quote)

Renal and electrolyte safety relative to investigator's choice in Part C
Safety populationPritelivir (n=51), n (%)Investigator's choice (n=50), n (%)
Renal or urinary disorders (adverse events of special interest)“3 (5.9)”“13 (26.0)”
Electrolyte abnormalities (adverse events of special interest)“1 (2.0)”“8 (16.0)”
Hematological adverse events (adverse events of special interest)“5 (9.8)”“14 (28.0)”
Hypokalemia“0”“7 (14.0)”
Hypomagnesemia“1 (2.0)”“6 (12.0)”
Treatment-emergent serious adverse events“10 (19.6)”“15 (30.0)”
Treatment discontinuation due to any treatment-emergent adverse event“2 (3.9)”“11 (22.0)”
Treatment discontinuation due to drug-related treatment-emergent adverse events“1 (2.0)”“10 (20.0)”

“Pritelivir was associated with fewer renal, electrolyte events and drug-related TEAE discontinuations (2.0%) compared with ICT (20.0%).” (opens the source at this quote in a new tab)

Renal and electrolyte safety relative to foscarnet in the phase 2 Part A

“As expected with the use of foscarnet, there were 2 renal-related TEAEs (increased creatinine and acute kidney injury) and 6 electrolyte abnormalities (hypernatremia, hypocalcemia, hyper- and hypophosphatemia) in the foscarnet arm whereas none were reported in the pritelivir arm.” (opens the source at this quote in a new tab)

Dosing in renal impairment

“No dose adjustment is recommended for patients with mild, moderate, or severe renal impairment.” (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)

Exposure and response

“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)