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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

Heterogeneity of treatment effect

31 evidence topics · 12 sources

Predefined subgroup analyses in PRIOH-1 Part C

“Secondary endpoints: % of patients with complete lesion healing up to 42 days of treatment; pre-defined subgroup analyses of % of patients with complete lesion healing up to 28 and 42 days of treatment” (opens the source at this quote in a new tab)

“The treatment difference is calculated as cure rate in the pritelivir treatment group minus the cure rate in the investigator’s choice treatment group. Comparisons are only populated for subgroup categories with at least 5 patients in both treatment groups.” (opens the source at this quote in a new tab)

“Pritelivir demonstrated consistent efficacious treatment effect across all subgroups, including in haematological malignancy, haematopoietic stem cell transplant and solid organ transplant recipients and patients living with HIV” (opens the source at this quote in a new tab)

Overall population as shown beside the subgroup analyses
PeriodPritelivir (N=51), m/M (%)Investigator's choice (N=50), m/M (%)Treatment difference, % (95% CI)
Up to 28 days of treatment“32/51 (62.7)”“17/50 (34.0)”“28.7 (8.0, 47.1)”
Up to 42 days of treatment“42/51 (82.4)”“21/50 (42.0)”“40.4 (20.7, 56.8)”
Adjustment of the primary analysis for protocol version

“The stratified Cochran-Mantel-Haenszel test was used to compare treatment groups, adjusting for protocol versions that reflected change in the control arm design.” (opens the prescribing information at this quote)

Underlying conditions represented in Part C: prescribing information

“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%).” (opens the prescribing information at this quote)

Underlying disease by treatment arm in Part C
Underlying diseasePritelivir (n=51), n (%)Investigator's choice (n=50), n (%)Total (n=101), n (%)
Stem cell transplant“14 (27.5)”“26 (52.0)”“40 (39.6)”
Solid organ transplant“2 (3.9)”“2 (4.0)”“4 (4.0)”
Hematological cancer or disorder“18 (35.3)”“29 (58.0)”“47 (46.5)”
Non-hematologic malignancy“10 (19.6)”“16 (32.0)”“26 (25.7)”
Autoimmune or inflammatory disease“19 (37.3)”“10 (20.0)”“29 (28.7)”
HIV infection“23 (45.1)”“15 (30.0)”“38 (37.6)”
Immunosuppressive condition categories used for the subgroup analyses

“Underlying Disease: Subjects may have more than one underlying condition, each subject is counted once under each applicable ‘Underlying Disease’ category.” (opens the source at this quote in a new tab)

“Immunosuppressive Condition: A subject is only counted under one ‘Immunosuppressive Condition’ category based on the hierarchy; Transplant; Oncology/autoimmune/inflammatory disorders; HIV Infection.” (opens the source at this quote in a new tab)

Immunosuppressive conditionPritelivir (n=51), n (%)Investigator's choice (n=50), n (%)Total (n=101), n (%)
Transplant“16 (31.4)”“28 (56.0)”“44 (43.6)”
Oncology, autoimmune, or inflammatory disorders“19 (37.3)”“15 (30.0)”“34 (33.7)”
HIV infection“16 (31.4)”“7 (14.0)”“23 (22.8)”
Transplant recipients: lesion healing in Part C
PeriodPritelivir, m/M (%)Investigator's choice, m/M (%)Treatment difference, % (95% CI)
Up to 28 days of treatment“8/16 (50.0)”“11/28 (39.3)”“10.7 (-20.3, 40.4)”
Up to 42 days of treatment“12/16 (75.0)”“14/28 (50.0)”“25.0 (-6.6, 51.0)”
Oncology and other non-transplant conditions: lesion healing in Part C
PeriodPritelivir, m/M (%)Investigator's choice, m/M (%)Treatment difference, % (95% CI)
Up to 28 days of treatment“13/19 (68.4)”“4/15 (26.7)”“41.8 (6.7, 69.0)”
Up to 42 days of treatment“17/19 (89.5)”“5/15 (33.3)”“56.1 (20.3, 80.0)”
People living with HIV: lesion healing in the hierarchical HIV category
PeriodPritelivir, m/M (%)Investigator's choice, m/M (%)Treatment difference, % (95% CI)
Up to 28 days of treatment“11/16 (68.8)”“2/7 (28.6)”“40.2 (-7.5, 73.7)”
Up to 42 days of treatment“13/16 (81.3)”“2/7 (28.6)”“52.7 (6.4, 83.1)”

“A broad range of immunocompromised conditions were included, among them 22.8% (23/101) PLHIV with a mean CD4 cell count of 350 cells/mm3” (opens the source at this quote in a new tab)

“In a subgroup analysis, 68.8% of the PLHIV in the pritelivir arm vs. 28.6% in the ICT arm had lesion healing with a treatment difference of 40.2% [95% CI: -7.5, 73.7], consistent with the overall positive treatment effect of pritelivir” (opens the source at this quote in a new tab)

People living with HIV: post hoc analysis of all 38 participants with HIV

“In the subgroup, people living with HIV represented 37.6% (38/101) of all immunocompromised patients enrolled in the PRIOH-1 Phase 3 trial and had a mean CD4 cell count of 334.8 cells/mm³.” (opens the source at this quote in a new tab)

“Among these patients, 81.6% (31/38) had refractory HSV (no clinical improvement in HSV lesions after ≥ 7 days of treatment), and 18.4% (7/38) had laboratory-confirmed acyclovir resistance. 40% of the study cohort had another underlying immunosuppressive condition.” (opens the source at this quote in a new tab)

“Similar to other subgroups, pritelivir achieved superior lesion healing of 61% (14/23) within up to 28 days of treatment, compared with 20% (3/15) for ICT, with an adjusted treatment difference of 37%, p = 0.027 [95%CI 7.6, 66.8] (post-hoc analysis).” (opens the source at this quote in a new tab)

“The majority (96%) of people living with HIV completed pritelivir treatment compared with 60% in the investigator’s choice treatment group.” (opens the source at this quote in a new tab)

PeriodPritelivir, healedPritelivir, %Investigator's choice, healedInvestigator's choice, %DifferenceP value
Up to day 28“n= 14/23”“61%”“n= 3/15”“20%”“37%”“p=0.0265”
Up to day 42“n= 18/23”“78%”“n= 4/15”“27%”“46%”“p=0.0046”
People living with HIV: antiretroviral therapy, CD4 count, and comparator received

“All patients in the HIV subgroup were on antiretroviral (ARV) therapy at baseline.” (opens the source at this quote in a new tab)

CharacteristicPritelivir (N=23)Investigator's choice (N=15)Total (N=38)
CD4 count, cells/mm3, mean (SD)“349.0 (242.9)”“314.8 (226.9)”“334.8 (233.6)”
CD4 count below 200 cells/mm3, n (%)“7 (33.3)”“7 (46.7)”“14 (36.8)”
Refractory HSV (clinical failure), n (%)“20 (87.0)”“11 (73.3)”“31 (81.6)”
Laboratory-confirmed acyclovir resistance, n (%)“3 (13.0)”“4 (26.7)”“7 (18.4)”
Investigator's choice treatment in the HIV subgroupParticipants (N=15), n (%)
Foscarnet, intravenous“7 (47)”
Imiquimod, topical“6 (40)”
Cidofovir, topical“2 (13)”
Documented acyclovir resistance against refractory infection without documented resistance: participants at baseline
Reason for treatment startPritelivir (n=51), n (%)Investigator's choice (n=50), n (%)Total (n=101), n (%)
Refractory HSV (clinical failure)“39 (76.5)”“33 (66.0)”“72 (71.3)”
Laboratory-confirmed acyclovir resistance“12 (23.5)”“17 (34.0)”“29 (28.7)”
Documented acyclovir resistance against refractory infection without documented resistance: lesion healing in Part C
Subgroup and periodPritelivir, n/N (%)Investigator's choice, n/N (%)Treatment difference, % (95% CI)
Laboratory-confirmed resistance, up to 28 days“11/22 (50.0)”“10/34 (29.4)”“20.6 (-6.9, 45.7)”
Resistance not detected or not evaluable, up to 28 days“21/29 (72.4)”“7/16 (43.8)”“28.7 (-2.2, 56.2)”
Laboratory-confirmed resistance, up to 42 days“17/22 (77.3)”“14/34 (41.2)”“36.1 (7.0,58.2)”
Resistance not detected or not evaluable, up to 42 days“25/29 (86.2)”“7/16 (43.8)”“42.5 (10.7,68.0)”

“Treatment effect favors pritelivir whether laboratory confirmed ACV resistance (ACV R) is present or not up to 28 days, with further improvement up to 42 days of treatment” (opens the source at this quote in a new tab)

HSV type: distribution at baseline in Part C

“HSV-1 and HSV-2 were identified in 31.7% and 45.5% of patients, respectively; HSV was unspecified/not detected at baseline in 22.8% of patients.” (opens the source at this quote in a new tab)

Lesion healing by HSV type in Part C

No evidence found.

Lesion healing by lesion site in Part C

No evidence found.

Comparator received: lesion healing in Part C by investigator's choice treatment

“Pritelivir Demonstrated Consistently Higher Efficacy vs ICT, Regardless of Choice of ICT” (opens the source at this quote in a new tab)

Investigator's choice treatmentHealed up to 28 days, m/M (%)Difference from pritelivir up to 28 days, % (95% CI)Healed up to 42 days, m/M (%)Difference from pritelivir up to 42 days, % (95% CI)
Foscarnet, intravenous“12/35 (34.3)”“28.5 (4.1, 48.0)”“14/35 (40.0)”“42.4 (19.1, 60.7)”
Cidofovir, intravenous“3/6 (50.0)”“12.7 (-26.3, 51.6)”“4/6 (66.7)”“15.7 (-15.3, 59.1)”
Cidofovir, topical“0/2 (0.0)”“NC”“1/2 (50.0)”“NC”
Imiquimod 5%, topical“2/7 (28.6)”“34.2 (-10.4, 62.2)”“2/7 (28.6)”“53.8 (3.7, 80.6)”
Region: lesion healing in Part C
Subgroup and periodPritelivir, m/M (%)Investigator's choice, m/M (%)Treatment difference, % (95% CI)
United States, up to 28 days“14/27 (51.9)”“7/28 (25.0)”“26.9 (0.1, 50.6)”
Outside the United States, up to 28 days“18/24 (75.0)”“10/22 (45.5)”“29.5 (-0.1, 55.3)”
United States, up to 42 days“21/27 (77.8)”“10/28 (35.7)”“42.1 (15.0, 64.4)”
Outside the United States, up to 42 days“21/24 (87.5)”“11/22 (50.0)”“37.5 (9.2, 61.2)”
Sex: lesion healing in Part C
Subgroup and periodPritelivir, m/M (%)Investigator's choice, m/M (%)Treatment difference, % (95% CI)
Male, up to 28 days“21/32 (65.6)”“9/21 (42.9)”“22.8 (-5.3, 48.6)”
Female, up to 28 days“11/19 (57.9)”“8/29 (27.6)”“30.3 (0.5, 56.6)”
Male, up to 42 days“27/32 (84.4)”“11/21 (52.4)”“32.0 (4.0, 57.0)”
Female, up to 42 days“15/19 (78.9)”“10/29 (34.5)”“44.5 (12.1, 67.5)”
Age: lesion healing in Part C
Subgroup and periodPritelivir, m/M (%)Investigator's choice, m/M (%)Treatment difference, % (95% CI)
Age 18 to 44 years, up to 28 days“16/21 (76.2)”“4/11 (36.4)”“39.8 (1.1, 69.6)”
Age 45 to 64 years, up to 28 days“12/20 (60.0)”“8/23 (34.8)”“25.2 (-5.7, 52.9)”
Age 65 years or older, up to 28 days“4/10 (40.0)”“5/16 (31.3)”“8.8 (-29.0, 47.5)”
Age 18 to 44 years, up to 42 days“17/21 (81.0)”“4/11 (36.4)”“44.6 (7.9, 73.4)”
Age 45 to 64 years, up to 42 days“16/20 (80.0)”“10/23 (43.5)”“36.5 (5.9, 62.0)”
Age 65 years or older, up to 42 days“9/10 (90.0)”“7/16 (43.8)”“46.3 (6.4, 73.8)”
Age 65 years or older: prescribing information

“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)

Race: lesion healing in Part C
Subgroup and periodPritelivir, m/M (%)Investigator's choice, m/M (%)Treatment difference, % (95% CI)
American Indian or Alaska Native, up to 28 days“9/11 (81.8)”“3/5 (60.0)”“21.8 (-26.1, 71.6)”
Asian, up to 28 days“1/1 (100)”“0/2 (0.0)”“NC”
Black or African American, up to 28 days“6/14 (42.9)”“1/9 (11.1)”“31.7 (-11.2, 63.5)”
White, up to 28 days“13/20 (65.0)”“12/29 (41.4)”“23.6 (-5.7, 49.6)”
Other, up to 28 days“3/5 (60.0)”“1/5 (20.0)”“40.0 (-30.5, 86.7)”
American Indian or Alaska Native, up to 42 days“11/11 (100)”“3/5 (60.0)”“40.0 (-1.2, 85.3)”
Asian, up to 42 days“1/1 (100)”“0/2 (0.0)”“NC”
Black or African American, up to 42 days“10/14 (71.4)”“2/9 (22.2)”“49.2 (2.8, 78.9)”
White, up to 42 days“17/20 (85.0)”“14/29 (48.3)”“36.7 (7.5, 59.2)”
Other, up to 42 days“3/5 (60.0)”“2/5 (40.0)”“20.0 (-47.5, 75.7)”
Foscarnet-refractory or foscarnet-intolerant participants: Parts D and F

“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).” (opens the prescribing information at this quote)

“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)

Foscarnet-refractory or foscarnet-intolerant participants: phase 2 Part B

“For Part B enrollment, participants had ACV R ± R HSV infections with additional foscarnet refractoriness with or without resistance (FOS R ± R) or intolerance (FOS-I).” (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)

“Of 8 patients, 5 (62.5%) healed and 3 (37.5%) did not. One of 5 healed participants experienced a recurrence.” (opens the source at this quote in a new tab)

“No instances of resistance to pritelivir were identified in Part B.” (opens the source at this quote in a new tab)

Non-randomized cohorts, including acyclovir-sensitive participants

“In addition, HSV patients were treated with pritelivir in two additional non-randomized cohorts: one study-arm included 35 patients who were R±R to acyclovir and foscarnet or intolerant to foscarnet, the second study-arm included 21 acyclovir-sensitive patients.” (opens the source at this quote in a new tab)

Lesion healing in acyclovir-sensitive participants

No evidence found.

Exposure, response, and pharmacokinetics across immunocompromising conditions

“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)

“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)

Company statements on consistency across subgroups

“Pritelivir demonstrated consistent treatment effects across major immunocompromised subgroups, including patients with hematological malignancies, hematopoietic stem cell and solid organ transplant recipients, and people living with HIV” (opens the source at this quote in a new tab)

“This efficacy response is independent of the patient’s underlying immunosuppressive disease.” (opens the source at this quote in a new tab)

Heterogeneity of underlying conditions in the phase 2 parts

“Study limitations include the small sample size, inherent to early-phase studies in uncommon and severe conditions, and the heterogeneity of the underlying immunosuppressive conditions, which were not stratified by design.” (opens the source at this quote in a new tab)

Populations not enrolled: ocular, central nervous system, and disseminated disease

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

Populations not enrolled: participants with myelosuppression

“On the basis of these findings, patients with myelosuppression are excluded from the ongoing clinical trial for immunocompromised patients with R/R HSV infections (NCT03073967).” (opens the source at this quote in a new tab)

Pediatric patients

“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)

“It is not known if HOVILPRI is safe and effective in children less than 18 years of age.” (opens the prescribing information at this quote)

“A total of 87.5% of patients ( n = 7) were treated with second‐line antivirals (foscarnet and/or cidofovir), and three patients were treated with third‐line antivirals (pritelivir).” (opens the source at this quote in a new tab)

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)

“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)

Hemodialysis and severe hepatic impairment

“No dose adjustment is recommended for patients with mild, moderate, or severe renal impairment. The pharmacokinetics and safety of pritelivir in patients requiring hemodialysis have not been evaluated” (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)