Primary objective: efficacy of oral pritelivir against intravenous foscarnet in Part A

“The primary objective of this Phase 2 study was to evaluate the efficacy of oral pritelivir vs intravenous (IV) foscarnet in immunocompromised adults with ACV R ± R HSV infections, with treatments administered for up to 28 days (Part A).” (opens the source at this quote in a new tab)

Secondary objectives: safety in Part A, and efficacy and safety in Part B

“Secondary objectives included assessing the safety of pritelivir compared with foscarnet in immunocompromised adults with ACV R ± R HSV infections (Part A), as well as evaluating pritelivir's efficacy and safety in participants with ACV R ± R and FOS R ± R or FOS-I HSV infections as secondary objectives in Part B.” (opens the source at this quote in a new tab)

Scope of the publication within the phase 2/3 trial

“Herein we report the results of the Phase 2 portion of the clinical trial.” (opens the source at this quote in a new tab)

Objective stated in the congress abstract

“We report the efficacy and safety of oral pritelivir versus foscarnet in a Phase 2 randomized, open label, multi-center comparative trial for the treatment of ACV R/R HSV in IC host; additional subjects received open label pritelivir for foscarnet resistant /intolerance (R/I) infection.” (opens the source at this quote in a new tab)

Objective stated by the sponsor when the first site opened

“The PRIOH-1 study announced today is a multi-center, randomized, open label phase 2 trial designed to evaluate the efficacy and safety of oral pritelivir compared to i.v. foscarnet, a virostatic agent which is used mainly for the treatment of herpes viruses resistant to other antiviral drugs.” (opens the source at this quote in a new tab)

Study centers

“The study took place in 14 centers across the United States.” (opens the source at this quote in a new tab)

Screening period

“Between October 7, 2017, and May 5, 2020, 29 patients were screened, with 1 withdrawing consent before enrollment.” (opens the source at this quote in a new tab)

First site opening and planned number of sites, sponsor release at trial initiation

“Wuppertal, May 09, 2017 - AiCuris Anti-infective Cures GmbH, a leading company in the discovery and development of drugs against infectious diseases, today announced the opening of the first site in its clinical phase 2 study, PRIOH-1, to evaluate the efficacy and safety of oral pritelivir, a small molecule helicase-primase inhibitor for the treatment of acyclovir-resistant mucocutaneous herpes simplex virus (HSV) infections in immunocompromised adults.” (opens the source at this quote in a new tab)
“The primary endpoint of the study which is planned to include a total of 30 patients at approx. 20 sites in the U.S. is time to lesion healing.” (opens the source at this quote in a new tab)

Number of sites as reported in the sponsor release on the phase 3 start

“In the phase 2 part of the trial, conducted at 20 sites in the US, 22 immunocompromised patients with acyclovir-resistant mucocutaneous HSV infections were randomized (2:1) to receive over a period of up to 28 days either oral pritelivir or intravenously administered foscarnet, a virostatic agent which is mainly used for the treatment of herpes virus infections resistant to other antiviral drugs.” (opens the source at this quote in a new tab)

Registry record: protocol number, start date, and status of the phase 2 parts

Field	Quoted record
Other study identifier	“AIC316-03-II-01”
Study start (actual)	“2017-05-08”
Status of Parts A and B	“Part A and Part B (Phase 2) have been finalised.”

European Union trial number named with the phase 2 results

“Aicuris presented a comprehensive update on pritelivir, including Phase 2 results (2023-510088-37-00) comparing the candidate to foscarnet (Fos) in immunocompromised patients infected with refractory mucocutaneous HSV with or without resistance (R±R).” (opens the source at this quote in a new tab)

Congress presentation of the phase 2 results

“Session: 88. New Anti-Infective Agents” (opens the source at this quote in a new tab)
“Monday, October 20, 2025: 3:51 PM” (opens the source at this quote in a new tab)

Two parts within the phase 2 portion of a phase 2/3 trial

“The Phase 2 portion of the Phase 2/3 PRIOH-1 study (Clinical Trials registration NCT03073967) comprised 2 parts: Part A, a randomized (2:1, pritelivir:foscarnet), open-label, multicenter, comparative study, and Part B, a multicenter study providing open-label pritelivir only.” (opens the source at this quote in a new tab)

Randomization ratio and open-label allocation

“In Part A, participants were randomized 2:1 to receive either open-label oral pritelivir or IV foscarnet. In Part B, all participants were treated with open-label pritelivir without a comparator, including those who switched from Part A due to FOS R ± R or FOS-I.” (opens the source at this quote in a new tab)

Transfer from Part A to Part B and washout

“Refractoriness or intolerance to foscarnet could be present at initial presentation or develop during Part A, allowing participants to switch to Part B.” (opens the source at this quote in a new tab)
“A 3-day washout period was mandated for participants treated with foscarnet in Part A switching to Part B.” (opens the source at this quote in a new tab)

Lesion assessment: index lesion, standardized photography, blinded review, and participant diary

“At randomization (Part A) or day 1 (Part B), the largest mucocutaneous lesion (index lesion) was identified for photographic documentation and lesion assessment (healing and size). Additional photographs were taken as needed to identify index lesion body location and the presence of other nonindex lesions. Standardized photographic equipment and procedures were employed for consistent, accurate lesion documentation across sites. Two independent reviewers conducted a blinded assessment of photographs. Participants maintained a daily diary to record lesion presence (existing or new) and document the timing of complete lesion healing.” (opens the source at this quote in a new tab)

Virologic sampling, central laboratory testing, and resistance testing

“Swabs were taken by investigational site staff every other day at each visit if lesions were present and evaluated by real-time qPCR TaqMan assay at a central laboratory (University of Washington Virology Laboratory)” (opens the source at this quote in a new tab)
“for HSV detection, HSV type, and copy number. Swabs were considered positive for HSV when at least 150 (2.2 log10) HSV DNA copies/mL were detected. Testing for resistance to ACV or trial medication was conducted using genotypic or phenotypic assays in the same laboratory.” (opens the source at this quote in a new tab)

Safety monitoring and grading of adverse events

“Safety assessments comprised continuous monitoring and recording of adverse events (AEs), laboratory parameters, and vital signs. AEs were evaluated by examining the rate, nature, duration, and severity, which were systematically recorded and graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (version 2.0, November 2014). All deaths attributed to an AE were classified as Grade 5. AEs of special interest (AESIs) included cutaneous, hematological, and coagulation AEs.” (opens the source at this quote in a new tab)

Treatment and follow-up periods shown in the congress slides

Design element	Quoted slide text
Part A population	“ACV Refractory ± Resistant”
Part B population	“ACV/FOS Refractory ± Resistant or FOS intolerant”
Treatment period	“Treatment up to 28 days”
Follow-up period	“Follow-up of 28 days”

Trial conduct, consent, and safety oversight

“The trial was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines as defined by the International Conference on Harmonisation. An independent Drug Safety Monitoring Board reviewed safety data.” (opens the source at this quote in a new tab)
“All participants provided written informed consent before enrollment. The trial protocol was reviewed and approved by all institutional review boards.” (opens the source at this quote in a new tab)

Registry description of Parts A and B

“The trial comprises 5 Parts, Part A, B, C, D, E and F.” (opens the source at this quote in a new tab)
“Part A is a randomized, open-label, multi-center, comparative design to assess the efficacy and safety in subjects with ACV-resistant mucocutaneous HSV infection, treated with oral pritelivir or intravenous foscarnet.” (opens the source at this quote in a new tab)
“Part B is an open-label, multi-center design to assess the efficacy and safety of pritelivir in subjects with ACV-resistant-mucocutaneous HSV and who either:” (opens the source at this quote in a new tab)
“present with foscarnet-resistance/intolerance, or” (opens the source at this quote in a new tab)
“developed foscarnet resistance/intolerance during treatment in Part A (no improvement after at least 5 days of foscarnet therapy or intolerance to foscarnet requiring cessation of foscarnet treatment).” (opens the source at this quote in a new tab)

Design as announced by the sponsor at trial initiation

“Patients will be randomized (2:1) to receive either pritelivir or foscarnet for up to 28 days.” (opens the source at this quote in a new tab)

Amendment of the trial to add the phase 3 part

“Following the strong results achieved in phase 2, AiCuris directly amended this trial with a pivotal phase 3 part as a basis for NDA submission.” (opens the source at this quote in a new tab)

“The encouraging results from this study supported the early transition of pritelivir into Phase 3 clinical development.” (opens the source at this quote in a new tab)

Population common to both parts

“Eligible participants were immunocompromised adults (≥18 years), male or female.” (opens the source at this quote in a new tab)

Part A: acyclovir-refractory infection with or without resistance

“For Part A enrollment, participants had ACV R ± R HSV infections defined by clinical failure (no improvement after ≥5 days of FDA-approved high-dose [nonprophylactic] ACV, valacyclovir, or famciclovir) and/or laboratory-confirmed genotypic/phenotypic resistance for current mucocutaneous HSV lesion(s). Resistance to ACV was confirmed by central laboratory genotypic testing. Phenotypic testing was conducted if genotypic testing was inconclusive.” (opens the source at this quote in a new tab)

Part B: additional foscarnet refractoriness, resistance, or intolerance

“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). Refractoriness was defined by clinical failure (no improvement after ≥5 days of foscarnet therapy) or laboratory-confirmed genotypic/phenotypic resistance test of samples from mucocutaneous lesions.” (opens the source at this quote in a new tab)
“Manifestations of foscarnet intolerance necessitating cessation of foscarnet treatment can be found in the Study Protocol” (opens the source at this quote in a new tab)

Key exclusion criteria

“Key exclusion criteria included known resistance or intolerance to pritelivir or foscarnet (Part A) and known intolerance to pritelivir (Part B).” (opens the source at this quote in a new tab)

Key inclusion criteria as presented in the congress slides

Criterion	Quoted slide text
Part A, immune status	“Immunocompromised adults (including, HIV infection, HCT, solid organ transplantation, chronic glucocorticoid use)”
Part A, infection	“refractory ± resistant mucocutaneous HSV infection based on:”
Part A, clinical failure	“clinical failure/refractory (no improvement after at least 5 days with FDA-approved treatment doses of a nucleoside analogue)”
Part A, laboratory resistance	“positive genotypic/phenotypic resistance testing”
Part B, immune status	“Identical as Part A”
Part B, infection	“ACV/FOS refractory ± resistant or FOS intolerant infection based on any of the following:”
Part B, clinical failure	“clinical failure/refractory (no improvement after at least 5 days of foscarnet therapy)”
Part B, intolerance	“FOS intolerance (requiring cessation of foscarnet treatment)”
Standard of care named in the footnote	“Standard of care treatment includes acyclovir, valacyclovir, famciclovir”

Registry description of the Part B population

“developed foscarnet resistance/intolerance during treatment in Part A (no improvement after at least 5 days of foscarnet therapy or intolerance to foscarnet requiring cessation of foscarnet treatment).” (opens the source at this quote in a new tab)

Definition of refractory infection given in the article's introduction

“HSV infection may become refractory to standard antiviral treatment, defined as a lack of clinical response after at least 7 days of therapy, often due to a lack of immune response, suboptimal drug exposure, and/or antiviral resistance frequently caused by mutations in the TK (UL23) gene” (opens the source at this quote in a new tab)

Consensus definitions of refractory and resistant infection shown in the congress slides

“Lack of clinical improvement in HSV-positive lesion(s) after at least 7 days of appropriately dosed anti-viral therapy” (opens the source at this quote in a new tab)
“New HSV positive lesion(s) after receiving appropriately dosed antiviral therapy for at least 7 days (excluding prophylaxis and suppressive therapy)” (opens the source at this quote in a new tab)
“A refractory HSV infection with viral genetic alteration(s) that decreases susceptibility and/or phenotypic assay demonstrating increased IC50 above the assay cutoff to one or more antiviral drug(s)” (opens the source at this quote in a new tab)

Relation of the enrolled population to the consensus definitions

“Until recently, a consensus definition of refractory and resistant HSV infection was lacking. The Transplant-Associated Virus Infections (TAVI) Forum Group has published standardized definitions and management guidance for refractory and resistant HSV infections in immunocompromised hosts” (opens the source at this quote in a new tab)
“These definitions align closely with the clinical characteristics of the participants included in PRIOH-1, supporting the external validity and clinical relevance of the findings.” (opens the source at this quote in a new tab)

Pritelivir regimen in Parts A and B

“In both study parts, 100 mg of pritelivir was administered orally, once daily, following an initial 400-mg loading dose administered orally on day 1. Treatment continued until 7 days after complete lesion healing or for a maximum of 28 days, whichever occurred first.” (opens the source at this quote in a new tab)

Intravenous foscarnet regimen in Part A

“In Part A, foscarnet was administered IV (40 mg/kg q8h or 60 mg/kg q12h, adjusted for renal impairment), with infusions lasting ≥1 hour. Foscarnet treatment continued until 7 days post–lesion healing or up to a maximum of 28 days.” (opens the source at this quote in a new tab)

Regimens as stated in the congress abstract

“In Part A, immunocompromised adult subjects with ACV-R/R HSV infection were randomized (2:1) to oral pritelivir (100 mg orally once daily, following a loading dose of 400 mg on Day 1) or IV foscarnet (120mg/kg/day divided every 8 or 12 hrs) for up to 28 days. In Part B, subjects with foscarnet R/I infection received open label pritelivir.” (opens the source at this quote in a new tab)

Regimens as shown in the congress slides

Arm	Quoted slide text
Pritelivir, Parts A and B	“Pritelivir 100 mg QD, following 400 mg loading dose”
Foscarnet, Part A	“Foscarnet IV, 40 mg/kg TID or 60 mg/kg BID”

Duration of treatment exposure in Part A

“Treatment exposure was longer among those who received pritelivir, with a median (range) of 26.0 (20–30) days, compared with 19.0 (4–25) days in the foscarnet arm.” (opens the source at this quote in a new tab)
“Median treatment duration was shorter and more variable among participants receiving foscarnet compared with those treated with pritelivir. Greater variability in the treatment duration and early discontinuation in the foscarnet arm reflected the known limited tolerability of foscarnet” (opens the source at this quote in a new tab)

Foscarnet as a prohibited concomitant medication in Part B

“One reported TEAE of cytomegalovirus reactivation resulted in treatment discontinuation not attributed to the trial medication, which required administration of foscarnet, a prohibited concomitant medication.” (opens the source at this quote in a new tab)

Pritelivir regimen as described in the sponsor release on the congress presentation

“All pritelivir-treated patients received a daily dose of 100mg oral pritelivir for 28 days following an initial 400mg loading dose.” (opens the source at this quote in a new tab)

Pritelivir regimen as described in the congress case series of the phase 2 participants

“All patient reported in this case series received pritelivir in a Phase 2 study. There were treated in an open-label design with a 400 mg pritelivir oral loading dose followed by a 100 mg oral maintenance dose daily for up to 28 days.” (opens the source at this quote in a new tab)

Primary endpoint: definition, censoring, and confirmation by independent photographic review

“The primary efficacy end point was time to lesion healing, defined as complete epithelization of mucocutaneous HSV lesions within the 28-day treatment period, with any participants not healed being censored at day 29. This end point was confirmed by independent photographic review (IPR) of standardized lesion photographs and the absence of new lesion formation.” (opens the source at this quote in a new tab)

Rationale for the primary endpoint

“The efficacy end point of time to lesion healing during the 28-day treatment period was selected as a clinically meaningful measure of antiviral activity, although interpretation in this study was limited by the small sample size.” (opens the source at this quote in a new tab)

Primary endpoint as announced at trial initiation

“The primary endpoint of the study which is planned to include a total of 30 patients at approx. 20 sites in the U.S. is time to lesion healing.” (opens the source at this quote in a new tab)

Secondary efficacy endpoints: investigator-assessed time to healing, healing rate, and HSV DNA

“Analyses of time to lesion healing were also performed by the investigator (secondary end point). Additional key secondary efficacy end points included healing rate (proportion of participants with complete lesion healing by day 28 by both IPR and investigator assessment) and HSV DNA detection (mean log number of HSV DNA copies on HSV DNA–positive swabs from lesion[s] as detected by quantitative polymerase chain reaction [qPCR]).” (opens the source at this quote in a new tab)

Endpoints as listed in the abstract of the publication

“The primary end point was time to lesion healing; secondary end points included healing rate, HSV DNA detection, and resistance.” (opens the source at this quote in a new tab)

Independent photographic review compared with investigator assessment

“Although IPR assessments provide a standardized, objective measure of lesion healing, investigator assessments offered an important complementary perspective, based on direct and continuous clinical observations to capture the dynamic nature of HSV lesion evolution and resolution more comprehensively than static, image-based IPR reviews. Given the limited sample size and the complex clinical course of refractory HSV infections in immunocompromised patients, investigator assessments likely provided a more complete representation of clinically meaningful healing.” (opens the source at this quote in a new tab)

Choice of investigator-assessed healing rate as the endpoint for phase 3

“The consistent direction and magnitude of the treatment effect across both assessment methods reinforce the robustness of the efficacy findings for pritelivir. Consequently, lesion healing rate based on investigator assessment was considered a more appropriate and clinically relevant end point for Phase 3 development.” (opens the source at this quote in a new tab)

Endpoints as presented in the congress slides

“Time to lesion healing was the primary endpoint for Part A and B, but as study has progressed healing rate was deemed the most relevant endpoint” (opens the source at this quote in a new tab)
“Healing rate: number of subjects healed (all lesions) at Day 28” (opens the source at this quote in a new tab)
“Safety parameters include adverse events, safety labs, vital signs, ECGs up to Day 28 after last dose of trial medication” (opens the source at this quote in a new tab)

Healing rate as defined in the congress abstract

“Healing rate defined as complete epithelization of lesions, and safety were assessed up to Day 28.” (opens the source at this quote in a new tab)

Virologic outcome: threshold for a positive swab

“Swabs were considered positive for HSV when at least 150 (2.2 log10) HSV DNA copies/mL were detected.” (opens the source at this quote in a new tab)

Resistance outcome: participants tested

“Resistance to trial medication (genotypic/phenotypic) was investigated in participants whose lesions did not heal within 28 days.” (opens the source at this quote in a new tab)

Safety outcomes: adverse events of special interest

“AEs of special interest (AESIs) included cutaneous, hematological, and coagulation AEs.” (opens the source at this quote in a new tab)

Planned enrollment

“Part A planned to enroll 30 participants, with up to 25 for Part B.” (opens the source at this quote in a new tab)

Basis for the planned sample size

“Given the exploratory, proof-of-concept nature of this study and the uncommon nature of ACV R ± R HSV infections in immunocompromised patients, Part A aimed to enroll 30 participants (20 in the pritelivir arm, 10 in the foscarnet arm) to facilitate efficient recruitment and provide preliminary safety and antiviral efficacy data to inform the design and primary efficacy end point of the subsequent pivotal study.” (opens the source at this quote in a new tab)

Participants screened, enrolled, and treated

“Between October 7, 2017, and May 5, 2020, 29 patients were screened, with 1 withdrawing consent before enrollment. The remaining 28 participants were enrolled in Part A or B.” (opens the source at this quote in a new tab)
“Of the 28 participants, 22 were enrolled into Part A (15 randomized to pritelivir and 7 to foscarnet). Eight participants entered Part B, including 2 transferring from Part A. All participants received ≥1 dose of study treatment.” (opens the source at this quote in a new tab)

Reason enrollment ended below the planned number

“Enrollment was below the planned 30 participants due to the sponsor's decision to discontinue Phase 2 and transition into a global Phase 3 trial, with an adjusted design and end points informed by Phase 2 findings.” (opens the source at this quote in a new tab)

Participants in each analysis set of the publication's tables

Analysis	Part A, pritelivir	Part A, foscarnet	Part B, pritelivir
Baseline characteristics, full analysis set	“n = 15”	“n = 7”	“n = 8”

Participants as reported in the abstract of the publication

“Twenty-two participants enrolled in Part A, 8 in Part B.” (opens the source at this quote in a new tab)

Participants as reported in the congress abstract

“In Part A, 22 subjects were randomized, n=15 to pritelivir and n=7 to foscarnet. Part B enrolled 8 subjects.” (opens the source at this quote in a new tab)

Participants as reported in the sponsor release on the congress presentation

“In the multi-center study a total of 22 patients were randomized 2:1 and treated with pritelivir or Fos. 8 additional patients, that were also Fos R±R or Fos intolerant, were treated with pritelivir in a non-randomized arm.” (opens the source at this quote in a new tab)

Pritelivir recipients pooled across both parts in the congress slides

Group	Participants
Part A, pritelivir	“PRITELIVIR N= 15”
Part A, foscarnet	“FOSCARNET N=7”
Part B, pritelivir	“PRITELIVIR N= 8”
All parts, pritelivir	“PRITELIVIR N= 23”

Statistical power

“Study was not powered to detect statistical differences between randomized groups” (opens the source at this quote in a new tab)

Full analysis set and primary data source

“The primary end point, time to lesion healing, was analyzed for Part A in the full analysis set (FAS; all randomized participants who received at least 1 dose of study medication and had at least 1 postbaseline lesion assessment). IPR served as the primary data source.” (opens the source at this quote in a new tab)

Primary analysis: log-rank test, Kaplan-Meier estimates, and Cox model

“Time to lesion healing was compared between treatment arms using a 2-sided log-rank test at the 2-sided .05 significance level. Median times and 95% CIs were estimated via the Kaplan-Meier (KM) method. The magnitude of the treatment effect was quantified using a Cox proportional hazards model, reporting hazard ratios (HRs) with 95% CIs.” (opens the source at this quote in a new tab)

Censoring in the time-to-healing analysis

“Participants were censored if they discontinued treatment early or if they completed treatment but failed to achieve lesion healing within the maximum 28-day treatment period.” (opens the source at this quote in a new tab)
“Twenty-eight-day treatment period includes all lesion assessments up to and including day 1 post-treatment visit.” (opens the source at this quote in a new tab)

Analysis of secondary efficacy outcomes

“Data for secondary efficacy outcomes were summarized descriptively and, in Part A, by treatment arm. Categorical end points were compared using chi-square tests. Clinical viral detection was compared between treatment arms using a Poisson regression model with log-link including treatment as an explanatory variable. Time-to-event variables were summarized descriptively using the KM method and compared using Cox regression and log-rank tests.” (opens the source at this quote in a new tab)
“Continuous variables were compared using the Student t test or Wilcoxon rank-sum test where normality assumptions were not met.” (opens the source at this quote in a new tab)

Values reported as not estimable

“Values were considered not estimable (NE) when the median survival time or 95% CI could not be reliably estimated due to insufficient events or high censoring.” (opens the source at this quote in a new tab)

Confidence intervals and tests named in the efficacy table footnotes

“The median time to lesion healing and day-specific rate were estimated using the KM method. The 95% CI was calculated using the Brookmeyer-Crowley method with loglog transformation.” (opens the source at this quote in a new tab)
“P value is based on log-rank test.” (opens the source at this quote in a new tab)
“Percentage was calculated using the number of participants in the column heading as the denominator. The 95% exact binomial CI was calculated.” (opens the source at this quote in a new tab)
“The 95% exact CI was calculated; the P value was obtained using the Fisher exact test.” (opens the source at this quote in a new tab)

Analysis of Part B

“Part B was analyzed separately from Part A using descriptive statistics. Any median time-to-event estimates for a single treatment arm were calculated using the same method as in Part A.” (opens the source at this quote in a new tab)

Safety analysis set

“All participants received ≥1 dose of study treatment.” (opens the source at this quote in a new tab)
“SAS, safety analysis set” (opens the source at this quote in a new tab)

Counting rule for adverse events

“Although a participant may have had 2 or more AEs, the participant is counted only once within each SOC category. The same participant may contribute to 2 or more PTs in the same SOC category.” (opens the source at this quote in a new tab)

Statistical software

“All statistical analyses were performed using SAS, version 9.3 or higher.” (opens the source at this quote in a new tab)

Screening, enrollment, and allocation

“Between October 7, 2017, and May 5, 2020, 29 patients were screened, with 1 withdrawing consent before enrollment. The remaining 28 participants were enrolled in Part A or B.” (opens the source at this quote in a new tab)
“Of the 28 participants, 22 were enrolled into Part A (15 randomized to pritelivir and 7 to foscarnet). Eight participants entered Part B, including 2 transferring from Part A. All participants received ≥1 dose of study treatment.” (opens the source at this quote in a new tab)

Part A: treatment completion and discontinuation by arm

“In Part A, all participants randomized to pritelivir completed treatment; most participants in the foscarnet arm discontinued treatment prematurely (n = 5, 71.4%, due to AEs [n = 1], withdrawal of consent [n = 2], or transfer to Part B following foscarnet treatment failure [n = 2])” (opens the source at this quote in a new tab)

Part B: treatment discontinuation

“One reported TEAE of cytomegalovirus reactivation resulted in treatment discontinuation not attributed to the trial medication, which required administration of foscarnet, a prohibited concomitant medication.” (opens the source at this quote in a new tab)

Discontinuation because of adverse events, congress slides

Group	Participants with an adverse event leading to discontinuation, n (%)
Part A, pritelivir, N = 15	“0”
Part A, foscarnet, N = 7	“3(42.9)”
Part B, pritelivir, N = 8	“1 (12.5)”
All parts, pritelivir, N = 23	“1 (4.3)”

Early discontinuation in the congress case series of the phase 2 participants

“Three patients subsequently experienced full resolution, while one patient required foscarnet due to CMV reactivation, necessitating early discontinuation.” (opens the source at this quote in a new tab)

Baseline demographics and clinical characteristics, full analysis set

Baseline parameter	Part A, pritelivir, n = 15	Part A, foscarnet, n = 7	Part B, pritelivir, n = 8
Age at screening, median (minimum to maximum), years	“52.0 (31–70)”	“56.0 (45–68)”	“56.0 (26–69)”
Male, No. (%)	“7 (46.7)”	“4 (57.1)”	“2 (25.0)”
Female, No. (%)	“8 (53.3)”	“3 (42.9)”	“6 (75.0)”
White, No. (%)	“3 (20.0)”	“5 (71.4)”	“5 (62.5)”
Black or African American, No. (%)	“11 (73.3)”	“2 (28.6)”	“3 (37.5)”
Other race, No. (%)	“1 (6.7)”	“0”	“0”
Hispanic or Latino, No. (%)	“1 (6.7)”	“0”	“1 (12.5)”
Not Hispanic or Latino, No. (%)	“14 (93.3)”	“7 (100)”	“7 (87.5)”
HSV-1, from medical history, No. (%)	“4 (26.7)”	“4 (57.1)”	“2 (25.0)”
HSV-2, from medical history, No. (%)	“8 (53.3)”	“3 (42.9)”	“4 (50.0)”
Both HSV-1 and HSV-2, from medical history, No. (%)	“3 (20.0)”	“0”	“2 (25.0)”
Genital lesion site, No.	“10”	“3”	“6”
Oral lesion site, No.	“5”	“4”	“2”
Maximum length of lesion, mean (SD), mm	“24.3 (14.6)”	“30.0 (13.5)”	“36.7 (37.1)”
Maximum length of lesion, median (minimum to maximum), mm	“25.0 (5–50)”	“30.0 (10–52)”	“20.0 (7–110)”
Maximum width of lesion, mean (SD), mm	“15.5 (10.7)”	“20.1 (9.7)”	“19.5 (13.9)”
Maximum width of lesion, median (minimum to maximum), mm	“12.5 (3–40)”	“20.0 (5–35)”	“17.0 (5–41)”
Documented acyclovir resistance, No. (%)	“13 (86.7)”	“7 (100)”	“5”“(62.5)”
No documented acyclovir resistance, No. (%)	“2 (13.3)”	“0”	“3 (37.5)”
Most recent anti-HSV treatment before enrollment: any listed, No. (%)	“10 (66.7)”	“4 (57.1)”	“5 (62.5)”
Most recent anti-HSV treatment before enrollment: acyclovir, No. (%)	“1 (6.7)”	“0”	“0”
Most recent anti-HSV treatment before enrollment: foscarnet, No. (%)	“0”	“1 (14.3)”	“2 (25.0)”
Most recent anti-HSV treatment before enrollment: valacyclovir, No. (%)	“9 (60.0)”	“3 (42.9)”	“3 (37.5)”
Immune suppression from HIV, No. (%)	“8 (53.3)”	“2 (28.6)”	“2 (25.0)”
Immune suppression from hematopoietic cell transplant, No. (%)	“5 (33.3)”	“5 (71.4)”	“3 (37.5)”
Immune suppression from kidney transplant, No. (%)	“1 (6.7)”	“0”	“0”
Immune suppression from leukemia, No. (%)	“0”	“0”	“3 (37.5)”
Immune suppression from undifferentiated connective tissue disease, No. (%)	“1 (6.7)”	“0”	“0”

“For participants who transferred from Part A to Part B, only the most recent treatment before enrollment in Part A was considered; this applied to 1 participant in Part B.” (opens the source at this quote in a new tab)
“Obtained from medical history.” (opens the source at this quote in a new tab)
“Includes 2 participants with acyclovir resistance, determined in Part A.” (opens the source at this quote in a new tab)
“Includes both valacyclovir and valacyclovir hydrochloride.” (opens the source at this quote in a new tab)

Part A: comparability of the arms, race, and virus type

“Baseline demographics and clinical characteristics were comparable between treatment arms” (opens the source at this quote in a new tab)
“Age and sex distribution were similar, although a higher proportion of Black or African American participants were randomized to the pritelivir arm (73.3% vs 28.6%). The frequency of HSV-1 vs HSV-2 detection from lesions was lower among participants receiving pritelivir (26.7% vs 53.3%) than those receiving foscarnet (57.1% vs 42.9%). Three participants in the pritelivir arm had a history of dual HSV-1/HSV-2 infection; no such cases were reported in the foscarnet arm. Medical histories and concomitant and prior medications were generally consistent with the eligible population.” (opens the source at this quote in a new tab)

Part A: absolute neutrophil count and prior anti-HSV treatment

“Baseline mean (SD) absolute neutrophil counts (ANCs) were 3.18 (1.73)×109/L in the pritelivir arm (n = 14) and 4.40 (4.14)×109/L in the foscarnet arm (n = 7). Valacyclovir was the most used prior anti-HSV treatment in both arms.” (opens the source at this quote in a new tab)

Part A: cause of immunosuppression by arm

“The predominant etiology of immunosuppression differed between arms. In the pritelivir arm, approximately half of the patients had HIV infection (53.3%), with another third having undergone HCT (33.3%). All but 1 participant with HIV were confirmed to be receiving antiretroviral therapy” (opens the source at this quote in a new tab)
“In the foscarnet arm, most participants were immunocompromised following HCT (71.4%).” (opens the source at this quote in a new tab)

Part B: characteristics compared with pritelivir recipients in Part A

“The 8 participants in Part B had demographic and disease characteristics similar to those treated with pritelivir in Part A, although the proportion of participants with documented ACV resistance from medical history was lower (62.5% vs 86.7% in Part A) and hematologic malignancies were more common (37.5% vs none in Part A)” (opens the source at this quote in a new tab)
“Mean (SD) baseline and EoTr ANC was 2.43 (1.19)×109/L and 2.37 (1.63)×109/L, respectively.” (opens the source at this quote in a new tab)

Mean age as presented in the congress slides

Parameter	Part A, pritelivir, N = 15	Part A, foscarnet, N = 7	Part B, pritelivir, N = 8
Age at screening, mean ± SD, years	“53.0 ± 10.97”	“57.7 ± 9.07”	“54.4 ± 13.51”

Cause of immunosuppression across both parts, congress abstract

“40% of patients were immunocompromised due HIV and 47% due to transplant.” (opens the source at this quote in a new tab)

Underlying conditions in the congress case series of the phase 2 pritelivir recipients

“Of the 23 patients, 11 had HIV infection and 12 had malignancy, transplant or an autoimmune disease.” (opens the source at this quote in a new tab)

Primary endpoint in Part A: time to lesion healing by independent photographic review

“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). Overall, the likelihood of achieving healing at 28 days was higher with pritelivir than with foscarnet, although this difference was not statistically significant (HR, 2.70; 95% CI, 0.33–21.83; P = .34)” (opens the source at this quote in a new tab)

Time to lesion healing through the last study visit in Part A

“When assessed up to the last visit (including post-treatment follow-up), the HR was 3.34 (95% CI, 0.42–26.28; P = .23)” (opens the source at this quote in a new tab)

Primary and selected secondary efficacy endpoints in Part A, full analysis set

Efficacy end point	Pritelivir, n = 15	Foscarnet, n = 7	Hazard ratio or difference in percentage healed (95% CI), P value
Primary: time to lesion healing up to 28 days by independent photographic review, median (95% CI), days	“26.0 (13.0–31.0)”	“NE (20.0–NE)”	“2.70 (0.33–21.83), P = .34”
Secondary: time to lesion healing up to 28 days by investigator, median (95% CI), days	“19.0 (15.0–25.0)”	“21.0 (11.0–NE)”	“1.18 (0.38–3.63), P = .78”
Secondary: healing rate up to 28 days by investigator, No. (%)	“14 (93.3)”	“4 (57.1)”	“36.2 (−10.1 to 74.1), P = .077”
Secondary: healing rate up to 28 days by independent photographic review, No. (%)	“10 (66.7)”	“1 (14.3)”	“52.4 (6.4–84.1), P = .064”

“NE, not estimable as <50% were assessed as healed.” (opens the source at this quote in a new tab)

Healing rate by independent photographic review in Part A

“Healing rates by IPR were 66.7% in the pritelivir arm and 14.3% in the foscarnet arm, corresponding to a treatment difference of 52.4% (95% CI, 6.4%–84.1%; P = .064)” (opens the source at this quote in a new tab)

Healing rate and time to healing by investigator assessment in Part A

“Investigator assessment identified lesion healing in an additional 4 participants in the pritelivir arm and 3 participants in the foscarnet arm who were not classified as healed by IPR. 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)
“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)

HSV DNA detection in lesion swabs in Part A

“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 (P = .42)” (opens the source at this quote in a new tab)

Resistance to trial medication in Part A

“Resistance to trial medication (genotypic/phenotypic) was investigated in participants whose lesions did not heal within 28 days. 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)

Authors' discussion of the K355T substitution

“Finally, therapeutic failure was less frequent in the pritelivir arm, and the emergence of resistance was rare, occurring in only 1 person” (opens the source at this quote in a new tab)
“The HSV-2 UL5 K355T substitution, which maps to a site linked to reduced pritelivir susceptibility, emerged during treatment in this study. The homologous K356T substitution in HSV-1 UL5 had previously been described to confer resistance in vitro” (opens the source at this quote in a new tab)

Prescribing information: susceptibility reduction with the substitution detected in the phase 2 trial

“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)

Resistance rates among participants tested after treatment, congress poster

Arm	Rate	Participants with resistance of those tested
Pritelivir, Parts A and B combined	“4.8%”	“1/21”
Foscarnet	“20.0%”	“1/5”

“Denominator: number of subjects with post-treatment resistance testing” (opens the source at this quote in a new tab)

Lesion recurrence during follow-up in Part A

“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)

Part B: time to healing, healing rate, and recurrence

“Median time to lesion healing assessed by IPR within 28 days in Part B was 19.0 days; when followed through to the last study visit, times to healing were similar” (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)

Part B: viral detection and resistance

“Viral detection rates were comparable between pritelivir-treated participants across study parts” (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)

Results as summarized in the abstract of the publication

“In Part A, median time to healing was 26.0 days (95% CI, 13.0–31.0) with pritelivir, vs not estimable (95% CI, 20.0–NE) with foscarnet (HR, 2.7; 95% CI, 0.33–21.8; P = .34). Investigator-assessed healing rates were 93% with pritelivir and 57% with foscarnet, a 36.2% difference (95% CI, −10.1 to 74.1; P = .077). Postbaseline HSV DNA detection rates were 34.8% and 50.0%, respectively (P = .42).” (opens the source at this quote in a new tab)
“In Part B, the median time to healing was 19.0 days, with a 63% healing rate.” (opens the source at this quote in a new tab)

Lesion healing rates with confidence intervals, congress slides

Parameter	Part A, pritelivir, N = 15	Part A, foscarnet, N = 7	Part B, pritelivir, N = 8
Participants with healed lesions, n (%) [95% CI]	“14 (93.3) [68.1 to 99.8]”	“4 (57.1) [18.4 to 90.1]”	“5 (62.5) [24.5 to 91.5]”

“36.2% [95% CI: - 10.1% to 74.1%]” (opens the source at this quote in a new tab)
“Percentage is calculated using the number of subjects in the column heading as the determinator. The 95% exact binomial confidence interval is calculated.” (opens the source at this quote in a new tab)

Healing rates as reported in the congress abstract

“In Part A, 14 of 15 (93%) in the pritelivir arm and 4 of 7 (57%) in the foscarnet arm healed (95% CI -10,74), (p=0.0766). In Part B, 5 of 8 (62.6%) with foscarnet R/I HSV infection healed.” (opens the source at this quote in a new tab)

Healing rates as reported in sponsor releases

“Pritelivir showed numerically improved efficacy compared to Fos, with 93% vs. 57% of patients achieving lesion healing within 28 days of treatment.” (opens the source at this quote in a new tab)

“Based on investigator assessment pritelivir treatment showed a very good cure rate of 93.3% in acyclovir resistant infections.” (opens the source at this quote in a new tab)

Healing across all 23 pritelivir recipients, congress case series

“Of this cohort, 19 patients showed full resolution of their HSV-related lesions during the 28 day treatment period, while in 4 subjects lesions improved but did not completely heal during the observation period.” (opens the source at this quote in a new tab)
“Reasons for incomplete lesion resolution during the 28 day treatment period, were extensive lesions in one patient, one patient with resistance development, and one patient with lesions in the oral cavity. Three patients subsequently experienced full resolution, while one patient required foscarnet due to CMV reactivation, necessitating early discontinuation.” (opens the source at this quote in a new tab)

Overall proportion of pritelivir recipients with full lesion resolution, congress poster

“Phase 2 data showed that, overall, 83% of pritelivir-treated immunocompromised patients with refractory/resistant HSV infection achieved full lesion resolution with a favorable safety profile during up to 28 days of treatment.” (opens the source at this quote in a new tab)

Authors' interpretation of the efficacy results

“Despite the lack of statistical significance, the treatment differences demonstrated a beneficial effect numerically, with a higher lesion healing rate on pritelivir compared with foscarnet (93.3% vs 57.1%), justifying further clinical development of pritelivir.” (opens the source at this quote in a new tab)
“In summary, pritelivir demonstrated encouraging efficacy and a favorable safety profile in immunocompromised patients with ACV R ± R HSV infection.” (opens the source at this quote in a new tab)

Part A: adverse events, serious adverse events, and severity by arm

“All participants in the foscarnet arm reported at least 1 treatment-emergent AE (TEAE), compared with 60% in the pritelivir arm” (opens the source at this quote in a new tab)
“Serious TEAEs also occurred more frequently in the foscarnet arm (28.6%) than the pritelivir arm (20%). Study drug–related AEs were absent in the pritelivir arm but prevalent in foscarnet-treated participants (71.4%). Severe TEAEs (DAIDS Grade ≥3) occurred in 57.1% of foscarnet participants vs 13.3% in the pritelivir arm.” (opens the source at this quote in a new tab)

Part A: deaths

“Two deaths occurred in the foscarnet arm and 1 in the pritelivir arm; none were considered by the investigator to be related to study medications.” (opens the source at this quote in a new tab)

Part A: overview of treatment-emergent adverse events, safety analysis set

Type of adverse event, No. (%)	Pritelivir, n = 15	Foscarnet, n = 7
Any treatment-emergent adverse event	“9 (60.0)”	“7 (100.0)”
Treatment-emergent adverse event leading to discontinuation	“0”	“3 (42.9)”
Drug-related treatment-emergent adverse event	“0”	“5 (71.4)”
Treatment-emergent adverse event leading to death	“1 (6.7)”	“2 (28.6)”
Treatment-emergent serious adverse event	“3 (20.0)”	“2 (28.6)”
Drug-related treatment-emergent serious adverse event	“0”	“0”

Part A: treatment-emergent adverse events of special interest, safety analysis set

Adverse event of special interest, No. (%)	Pritelivir, n = 15	Foscarnet, n = 7
Any cutaneous event of special interest	“5 (33.3)”	“0”
Herpes simplex	“2 (13.3)”	“0”
Rash	“1 (6.7)”	“0”
Furuncle	“1 (6.7)”	“0”
Genital herpes simplex	“1 (6.7)”	“0”
Acute graft-vs-host disease in skin	“1 (6.7)”	“0”
Graft-vs-host disease in skin	“1 (6.7)”	“0”
Intertrigo	“1 (6.7)”	“0”
Any hematological event of special interest	“0”	“4 (57.1)”
Anemia	“0”	“1 (14.3)”
Hematocrit decreased	“0”	“1 (14.3)”
Hemoglobin decreased	“0”	“1 (14.3)”
Gastrointestinal hemorrhage	“0”	“1 (14.3)”
Hypogammaglobulinemia	“0”	“1 (14.3)”
Any coagulation event of special interest	“0”	“0”

“TEAEs of special interest were not derived using PTs but were recorded in the case report form.” (opens the source at this quote in a new tab)
“Participant was transferred to Part B from Part A and reported this TEAE of special interest in Part A.” (opens the source at this quote in a new tab)

Part A: adverse events with an incidence of 10% or more in either arm, by preferred term

Preferred term, No. (%)	Pritelivir, n = 15	Foscarnet, n = 7
Edema peripheral	“2 (13.3)”	“1 (14.3)”
Headache	“1 (6.7)”	“2 (28.6)”
Arthralgia	“2 (13.3)”	“0”
Herpes simplex	“2 (13.3)”	“0”
Atrial fibrillation	“1 (6.7)”	“1 (14.3)”
Blood creatinine increased	“1 (6.7)”	“1 (14.3)”
Fall	“1 (6.7)”	“1 (14.3)”
Hypertension	“1 (6.7)”	“1 (14.3)”
Hyperphosphatemia	“0”	“2 (28.6)”
Hypocalcemia	“0”	“2 (28.6)”
Acute kidney injury	“0”	“1 (14.3)”
Anemia	“0”	“1 (14.3)”
Cytomegalovirus	“0”	“1 (14.3)”
Constipation	“0”	“1 (14.3)”
Drug intolerance	“0”	“1 (14.3)”
Encephalopathy	“0”	“1 (14.3)”
Fluid overload	“0”	“1 (14.3)”
Hematocrit decreased	“0”	“1 (14.3)”
Hemoglobin decreased	“0”	“1 (14.3)”
Hepatic encephalopathy	“0”	“1 (14.3)”
Hyperglycemia	“0”	“1 (14.3)”
Hypernatremia	“0”	“1 (14.3)”
Hypophosphatemia	“0”	“1 (14.3)”
Nausea	“0”	“1 (14.3)”
Nephrogenic diabetes insipidus	“0”	“1 (14.3)”
Paresthesia	“0”	“1 (14.3)”
Pneumonia	“0”	“1 (14.3)”
Pneumonia fungal	“0”	“1 (14.3)”
Pulmonary mass	“0”	“1 (14.3)”
Septic shock	“0”	“1 (14.3)”

Part A: most common adverse events by arm

“The most common TEAEs in the foscarnet arm were headache (28.6%), hyperphosphatemia (28.6%), and hypocalcemia (28.6%). In the pritelivir arm, the most frequently reported TEAEs were peripheral edema (13.3%), arthralgia (13.3%), and HSV infection (13.3%).” (opens the source at this quote in a new tab)

Part A: renal events and electrolyte abnormalities

“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)

Part A: hematologic, coagulation, and cutaneous events of special interest

“Hematologic AESIs were reported only in the foscarnet arm, affecting 4 of 7 participants (57.1%), and there were no coagulation AESIs. Cutaneous AESIs occurred in 5 of 15 participants (33.3%) in the pritelivir arm; most events were related to HSV or graft-vs-host disease, with 1 case of rash reported. No cutaneous AESIs were observed in the foscarnet arm.” (opens the source at this quote in a new tab)

Part A: adverse events leading to discontinuation

“TEAEs leading to discontinuation in 3 foscarnet-treated participants were nausea, drug intolerance, blood creatinine increased, fluid overload, hypocalcemia, headache, and paresthesia, consistent with the known safety profile of foscarnet.” (opens the source at this quote in a new tab)
“No TEAEs leading to discontinuation were reported in the pritelivir arm.” (opens the source at this quote in a new tab)

Part A: vital signs, electrocardiogram, and laboratory parameters

“Overall, there were no clinically relevant trends in vital signs, electrocardiogram (ECG) or laboratory parameters, or physical examination following study treatment. Mean (SD) end-of-trial (EoTr) ANC was 3.16 (1.57)×109/L in the pritelivir arm (n = 12) and 8.73 (6.56)×109/L in the foscarnet arm (n = 3). Trends in laboratory parameters observed in the foscarnet arm were consistent with the known effects, including anemia and elevated serum amylase” (opens the source at this quote in a new tab)

Part B: adverse events, serious adverse events, and deaths

“All 8 participants in Part B reported at least 1 TEAE, and 3 reported a serious TEAE” (opens the source at this quote in a new tab)
“One drug-related SAE (rash) graded as severe (DAIDS Grade ≥3) resulted in participant hospitalization” (opens the source at this quote in a new tab)
“Severe TEAEs occurred in 4 of the 8 participants. No deaths were reported.” (opens the source at this quote in a new tab)

Part B: most frequent adverse events, including increased creatinine

“The most frequently reported TEAEs were headache (37.5%), diarrhea (25%), increased creatinine (25%), and rash (25%). One reported TEAE of cytomegalovirus reactivation resulted in treatment discontinuation not attributed to the trial medication, which required administration of foscarnet, a prohibited concomitant medication.” (opens the source at this quote in a new tab)

Part B: events of special interest, vital signs, and laboratory parameters

“Three participants reported cutaneous AESIs, and 2 participants reported hematological AESIs” (opens the source at this quote in a new tab)
“No coagulation AESIs were reported. As in Part A, no clinically relevant trends in vital signs, ECG or laboratory parameters, or physical examination following study treatment were observed.” (opens the source at this quote in a new tab)

Authors' discussion of tolerability and events of special interest

“In contrast, pritelivir was well tolerated, with fewer drug-related AEs, lower discontinuation rates, and no clinically significant laboratory abnormalities.” (opens the source at this quote in a new tab)
“In Part A, AESIs differed between treatment arms. Hematological TEAEs were observed in the foscarnet arm, whereas no such events were reported in the pritelivir arm. Hematological TEAEs were observed in Part B; of note, these participants had received foscarnet before pritelivir. In Part A, cutaneous AESIs were only reported in the pritelivir arm, with 1 event of rash; the remaining events were HSV or graft-vs-host disease related. One related SAE of rash was observed in Part B.” (opens the source at this quote in a new tab)

Safety as summarized in the abstract of the publication

“Treatment-emergent adverse events occurred in 60% of pritelivir- and 100% of foscarnet-treated participants; serious treatment-emergent adverse events were less frequent with pritelivir.” (opens the source at this quote in a new tab)

Overview of safety findings in Part A, Part B, and all pritelivir recipients, congress slides

Type of adverse event, n (%)	Part A, pritelivir, N = 15	Part A, foscarnet, N = 7	Part B, pritelivir, N = 8	All parts, pritelivir, N = 23
Any treatment-emergent adverse event	“9 (60)”	“7 (100)”	“8 (100)”	“17 (73.9)”
Non-serious treatment-emergent adverse event	“9 (60)”	“7 (100)”	“8 (100)”	“17 (73.9)”
Treatment-emergent serious adverse event	“3 (20)”	“2(28.6)”	“3 (37.5)”	“6 (26.1)”
Death	“1 (6.7)”	“2(28.6)”	“0”	“1 (4.3)”
Treatment-emergent adverse event leading to discontinuation	“0”	“3(42.9)”	“1 (12.5)”	“1 (4.3)”
Severe treatment-emergent adverse event (DAIDS Grade 3 or higher)	“2 (13.3)”	“4(57.1)”	“4 (50.0)”	“6 (26.1)”
Drug-related treatment-emergent serious adverse event	“0”	“0”	“1(12.5)”	“1 (4.3)”

Drug-related treatment-emergent adverse events by system organ class, congress slides

Type of adverse event, n (%)	Part A, pritelivir, N = 15	Part A, foscarnet, N = 7	Part B, pritelivir, N = 8	All parts, pritelivir, N = 23
Drug-related treatment-emergent adverse event	“0”	“5 (71.4)”	“2 (25)”	“2 (8.7)”
Gastrointestinal disorders	“0”	“2 (28.6)”	“1 (12.5)”	“1 (4.3)”
General disorders and administration site conditions	“0”	“2 (28.6)”	“0”	“0”
Investigations	“0”	“1 (14.3)”	“0”	“0”
Metabolism and nutrition	“0”	“2 (28.6)”	“1 (12.5)”	“1 (4.3)”
Nervous system disorders	“0”	“2 (28.6)”	“0”	“0”
Renal and urinary disorders	“0”	“1 (14.3)”	“0”	“0”
Skin and subcutaneous tissue disorders	“0”	“0”	“1 (12.5)”	“1 (4.3)”

“N=2 in the Foscarnet group reported headache and hyperphosphatemia” (opens the source at this quote in a new tab)

Safety conclusions in the congress slides

“Pritelivir showed a favorable safety profile and was generally well tolerated” (opens the source at this quote in a new tab)
“Discontinuation rates and drug-related TEAEs were higher for foscarnet than for pritelivir treated participants.” (opens the source at this quote in a new tab)

Treatment-related adverse events and discontinuations by part, congress poster

“Treatment Related adverse events (AE) Part A: pritelivir 0% (0/15) vs. foscarnet 71.4% (5/7); Part B: 2/8 (25.0%)” (opens the source at this quote in a new tab)
“AE related discontinuations Part A: pritelivir 0% (0/15) vs. foscarnet 42.9% (3/7); Part B: 1/8 (12.5%)” (opens the source at this quote in a new tab)

Discontinuation because of adverse events as reported in the congress abstract

“Treatment emergent adverse events leading to drug discontinuation were more common for foscarnet (43%) versus pritelivir (4%).” (opens the source at this quote in a new tab)

Discontinuation because of adverse events as reported in sponsor releases

“Pritelivir was associated with fewer adverse event-related discontinuations (0% vs. 42.9%).” (opens the source at this quote in a new tab)

“Pritelivir was safe and well tolerated. In none of the patients, treatment with pritelivir was prematurely discontinued due to adverse events during the trial.” (opens the source at this quote in a new tab)

Tolerability in the congress case series of the phase 2 pritelivir recipients

“Pritelivir was well tolerated without significant adverse effects.” (opens the source at this quote in a new tab)

Summary

Part A randomized 22 participants (15 to pritelivir, 7 to foscarnet) against a planned 30, after the sponsor ended phase 2 to begin phase 3; Part B treated 8 participants without a comparator. Treatment was open label, and the trial was not designed or powered to detect statistical differences. The primary endpoint did not differ significantly (hazard ratio 2.70; 95% CI 0.33 to 21.83; P = .34). Healing was recorded in 10 of 15 pritelivir recipients by independent photographic review and in 14 of 15 by investigators. Five of 7 foscarnet recipients stopped treatment early. The arms differed in race and in cause of immunosuppression, which was not a stratification factor. AiCuris funded the trial and employs three authors.

Limitations stated by the authors

“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. It is also important to note that this Phase 2 study was not designed or powered to detect statistical differences. 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)

Interpretation of the primary endpoint limited by sample size

“The efficacy end point of time to lesion healing during the 28-day treatment period was selected as a clinically meaningful measure of antiviral activity, although interpretation in this study was limited by the small sample size.” (opens the source at this quote in a new tab)

Statistical power as stated in the congress slides

“Study was not powered to detect statistical differences between randomized groups” (opens the source at this quote in a new tab)

Enrollment ended below the planned number

“Enrollment was below the planned 30 participants due to the sponsor's decision to discontinue Phase 2 and transition into a global Phase 3 trial, with an adjusted design and end points informed by Phase 2 findings.” (opens the source at this quote in a new tab)

Collection of adverse events of special interest

“Importantly, interpretation of these findings is limited by the method of data collection as TEAEs of special interest were recorded in case report forms rather than systematically derived from standardized PTs within system organ classes.” (opens the source at this quote in a new tab)

Confirmation sought in the phase 3 parts

“Further evaluation is ongoing in a global Phase 3 trial, which aims to confirm these findings in a larger and more diverse patient cohort.” (opens the source at this quote in a new tab)

Funding, sponsor employment of authors, and medical writing support

“This work was supported by AiCuris Anti-Infectives Cure AG.” (opens the source at this quote in a new tab)
“A.B., M.E.S., and B.S. are employees of AiCuris. M.Rang. and B.T. were former employees of AiCuris.” (opens the source at this quote in a new tab)
“Additional medical writing support was provided by Kara McNair, MediComm Partners, which was sponsored by AiCuris Anti-Infective Cures AG in accordance with Good Publication Practice guidelines.” (opens the source at this quote in a new tab)