Pritelivir: labeled indication

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

Pritelivir: pharmacologic class and target

“HOVILPRI is a herpes simplex virus (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)

Pritelivir: route, dose, and duration of treatment

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

Pritelivir: contraindications, warnings, and most common adverse reaction

Attribute	Prescribing information
Contraindications	“None.”
Warnings and precautions	“Concomitant use of HOVILPRI with certain acid-reducing agents may reduce pritelivir exposure, potentially resulting in reduced therapeutic effect and development of resistance.”
Most common adverse reaction	“The most common adverse reaction (incidence >5%) was headache.”
Hepatic laboratory abnormalities	“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”

Pritelivir: dosing in renal and 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)
“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)

Pritelivir: cross-resistance with nucleoside analogues and foscarnet

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

Pritelivir against investigator's choice in PRIOH-1 Part C: comparator treatments

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

Pritelivir against investigator's choice in PRIOH-1 Part C: lesion healing

Measure	Prescribing information
Response rate up to day 28, pritelivir	“32/51 (63%)”
Response rate up to day 28, investigator's choice	“17/50 (34%)”
Adjusted treatment difference (95% CI)	“28.4 (9.6, 47.3)”
p-value	“0.0047”

“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)

Pritelivir against investigator's choice in PRIOH-1 Part C: adverse reactions and discontinuations

“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)

Pritelivir after foscarnet failure or intolerance: PRIOH-1 Parts D and F

“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)

Intravenous foscarnet: labeled indication

“FOSCAVIR is indicated for the treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients.” (opens the source at this quote in a new tab)
“SAFETY AND EFFICACY OF FOSCAVIR HAVE NOT BEEN ESTABLISHED FOR TREATMENT OF OTHER HSV INFECTIONS (e.g., RETINITIS, ENCEPHALITIS); CONGENITAL OR NEONATAL HSV DISEASE; OR HSV IN NONIMMUNOCOMPROMISED INDIVIDUALS.” (opens the source at this quote in a new tab)

Intravenous foscarnet: boxed warning

“RENAL IMPAIRMENT IS THE MAJOR TOXICITY OF FOSCAVIR. FREQUENT MONITORING OF SERUM CREATININE, WITH DOSE ADJUSTMENT FOR CHANGES IN RENAL FUNCTION, AND ADEQUATE HYDRATION WITH ADMINISTRATION OF FOSCAVIR IS IMPERATIVE.” (opens the source at this quote in a new tab)
“SEIZURES, RELATED TO ALTERATIONS IN PLASMA MINERALS AND ELECTROLYTES, HAVE BEEN ASSOCIATED WITH FOSCAVIR TREATMENT. THEREFORE, PATIENTS MUST BE CAREFULLY MONITORED FOR SUCH CHANGES AND THEIR POTENTIAL SEQUELAE. MINERAL AND ELECTROLYTE SUPPLEMENTATION MAY BE REQUIRED.” (opens the source at this quote in a new tab)
“FOSCAVIR IS INDICATED FOR USE ONLY IN IMMUNOCOMPROMISED PATIENTS WITH CMV RETINITIS AND MUCOCUTANEOUS ACYCLOVIR-RESISTANT HSV INFECTIONS.” (opens the source at this quote in a new tab)

Intravenous foscarnet: route and administration

“FOSCAVIR is administered by controlled intravenous infusion, either by using a central venous line or by using a peripheral vein. The rate of infusion must be no more than 1 mg/kg/minute.” (opens the source at this quote in a new tab)
“An infusion pump must be used to control the rate of infusion.” (opens the source at this quote in a new tab)

Intravenous foscarnet: dose for acyclovir-resistant HSV

“For acyclovir-resistant HSV patients, 40 mg/kg (minimum one hour infusion) either every 8 or 12 hours for 2-3 weeks or until healed.” (opens the source at this quote in a new tab)
“ALL DOSES MUST BE INDIVIDUALIZED FOR PATIENTS’ RENAL FUNCTION.” (opens the source at this quote in a new tab)

Intravenous foscarnet: hydration with each infusion

“It is recommended that 750–1000 mL of normal saline or 5% dextrose solution should be given prior to the first infusion of FOSCAVIR to establish diuresis. With subsequent infusions, 750–1000 mL of hydration fluid should be given with 90–120 mg/kg of FOSCAVIR, and 500 mL with 40–60 mg/kg of FOSCAVIR.” (opens the source at this quote in a new tab)

Intravenous foscarnet: renal impairment warning and use in renal dysfunction

“Renal impairment is most likely to become clinically evident during the second week of induction therapy, but may occur at any time during FOSCAVIR treatment.” (opens the source at this quote in a new tab)
“Elevations in serum creatinine are usually, but not always, reversible following discontinuation or dose adjustment of FOSCAVIR.” (opens the source at this quote in a new tab)
“Safety and efficacy data for patients with baseline serum creatinine levels greater than 2.8 mg/dL or measured 24-hour creatinine clearances <50 mL/min are limited.” (opens the source at this quote in a new tab)
“FOSCAVIR is not recommended in patients undergoing hemodialysis because dosage guidelines have not been established.” (opens the source at this quote in a new tab)

Intravenous foscarnet: incidence of renal impairment, electrolyte changes, and seizures in labeled trials

“Approximately 33% of 189 patients with AIDS and CMV retinitis who received FOSCAVIR (60 mg/kg TID), without adequate hydration, developed significant impairment of renal function (serum creatinine ≥ 2.0 mg/dL).” (opens the source at this quote in a new tab)
“The incidence of renal impairment in subsequent clinical trials in which 1000 mL of normal saline or 5% dextrose solution was” (opens the source at this quote in a new tab)
“given with each infusion of FOSCAVIR was 12% (34/280).” (opens the source at this quote in a new tab)
“FOSCAVIR has been associated with changes in serum electrolytes including hypocalcemia (15–30%), hypophosphatemia (8–26%) and hyperphosphatemia (6%), hypomagnesemia (15–30%), and hypokalemia (16–48%)” (opens the source at this quote in a new tab)
“FOSCAVIR treatment was associated with seizures in 18/189 (10%) AIDS patients in the initial five controlled studies” (opens the source at this quote in a new tab)

Intravenous foscarnet: trials in acyclovir-resistant HSV described in the label

“In a controlled trial, patients with AIDS and mucocutaneous, acyclovir-resistant HSV infection were randomized to either FOSCAVIR (N=8) at a dose of 40 mg/kg TID or vidarabine (N=6) at a dose of 15 mg/kg per day.” (opens the source at this quote in a new tab)
“Lesions in the eight patients randomized to FOSCAVIR healed after 11 to 25 days; seven of the 11 patients nonrandomly treated with FOSCAVIR healed their lesions in 10 to 30 days. Vidarabine was discontinued because of intolerance (N=4) or poor therapeutic response (N=2).” (opens the source at this quote in a new tab)
“In a second trial, forty AIDS patients and three bone marrow transplant recipients with mucocutaneous, acyclovir-resistant HSV infections were randomized to receive FOSCAVIR at a dose of either 40 mg/kg BID or 40 mg/kg TID. Fifteen of the 43 patients had healing of their lesions in 11 to 72 days with no difference in response between the two treatment groups.” (opens the source at this quote in a new tab)

Intravenous foscarnet: relapse and resistance after treatment

“Patients should be advised that FOSCAVIR is not a cure for HSV infections. While complete healing is possible, relapse occurs in most patients.” (opens the source at this quote in a new tab)
“In addition, repeated treatment with FOSCAVIR has led to the development of resistance associated with poorer response.” (opens the source at this quote in a new tab)

Intravenous cidofovir: labeled indication

“Cidofovir is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS).” (opens the source at this quote in a new tab)
“CIDOFOVIR INJECTION IS INDICATED ONLY FOR THE TREATMENT OF CMV RETINITIS IN PATIENTS WITH ACQUIRED IMMUNODEFICIENCY SYNDROME.” (opens the source at this quote in a new tab)
“Controlled clinical studies of efficacy have been limited to patients with AIDS and CMV retinitis.” (opens the source at this quote in a new tab)

Intravenous cidofovir: boxed warning

“RENAL IMPAIRMENT IS THE MAJOR TOXICITY OF CIDOFOVIR INJECTION. CASES OF ACUTE RENAL FAILURE RESULTING IN DIALYSIS AND/OR CONTRIBUTING TO DEATH HAVE OCCURRED WITH AS FEW AS ONE OR TWO DOSES OF CIDOFOVIR INJECTION.” (opens the source at this quote in a new tab)
“TO REDUCE POSSIBLE NEPHROTOXICITY, INTRAVENOUS PREHYDRATION WITH NORMAL SALINE AND ADMINISTRATION OF PROBENECID MUST BE USED WITH EACH CIDOFOVIR INJECTION INFUSION.” (opens the source at this quote in a new tab)
“CIDOFOVIR INJECTION IS CONTRAINDICATED IN PATIENTS WHO ARE RECEIVING OTHER NEPHROTOXIC AGENTS.” (opens the source at this quote in a new tab)
“NEUTROPENIA HAS BEEN OBSERVED IN ASSOCIATION WITH CIDOFOVIR INJECTION TREATMENT. THEREFORE, NEUTROPHIL COUNTS SHOULD BE MONITORED DURING CIDOFOVIR INJECTION THERAPY.” (opens the source at this quote in a new tab)
“IN ANIMAL STUDIES CIDOFOVIR WAS CARCINOGENIC, TERATOGENIC AND CAUSED HYPOSPERMIA” (opens the source at this quote in a new tab)

Intravenous cidofovir: route and labeled dose

“FOR INTRAVENOUS INFUSION ONLY. NOT FOR INTRAOCULAR INJECTION.” (opens the source at this quote in a new tab)
“is 5 mg/kg body weight (given as an intravenous infusion at a constant rate over 1 hr) administered once weekly for two consecutive weeks.” (opens the source at this quote in a new tab)
“The recommended maintenance dose of cidofovir injection is 5 mg/kg body weight (given as an intravenous infusion at a constant rate over one hr), administered once every 2 weeks.” (opens the source at this quote in a new tab)

Intravenous cidofovir: renal contraindications

“Initiation of therapy with cidofovir injection is contraindicated in patients with a serum creatinine > 1.5 mg/dL, a calculated creatinine clearance ≤ 55 mL/min, or a urine protein ≥ 100 mg/dL (equivalent to ≥ 2+ proteinuria).” (opens the source at this quote in a new tab)
“Cidofovir injection is contraindicated in patients receiving agents with nephrotoxic potential. Such agents must be discontinued at least seven days prior to starting therapy with cidofovir injection.” (opens the source at this quote in a new tab)

Topical imiquimod: labeled indications and route

“ALDARA is indicated for the topical treatment of clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses (AK) on the face or scalp in immunocompetent adults.” (opens the source at this quote in a new tab)
“ALDARA is indicated for the topical treatment of biopsy-confirmed, primary superficial basal cell carcinoma (sBCC) in immunocompetent adults” (opens the source at this quote in a new tab)
“External genital and perianal warts (EGW) in immunocompetent patients 12 years of age and older.” (opens the source at this quote in a new tab)
“For topical use only; not for oral, ophthalmic, intra-anal or intravaginal use.” (opens the source at this quote in a new tab)

Intravenous acyclovir: labeled indication and dose for HSV in immunocompromised patients

“ZOVIRAX for Injection is indicated for the treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) in immunocompromised patients.” (opens the source at this quote in a new tab)
“Adults and Adolescents (Aged 12 years and older): 5 mg/kg infused at a constant rate over 1 hour, every 8 hours for 7 days.” (opens the source at this quote in a new tab)

Intravenous acyclovir: resistance statement in the label

“Clinical isolates of HSV and VZV with reduced susceptibility to acyclovir have been recovered from immunocompromised patients, especially with advanced HIV infection.” (opens the source at this quote in a new tab)
“The possibility of viral resistance to acyclovir should be considered in patients who show poor clinical response during therapy.” (opens the source at this quote in a new tab)

Oral acyclovir: labeled HSV indication

“Genital Herpes: ZOVIRAX is indicated for the treatment of initial episodes and the management of recurrent episodes of genital herpes.” (opens the source at this quote in a new tab)

Valacyclovir: labeled HSV indication in HIV infection and limitation in other immunocompromised patients

“VALTREX is indicated for chronic suppressive therapy of recurrent episodes of genital herpes in immunocompetent and in HIV-1−infected adults.” (opens the source at this quote in a new tab)
“The efficacy and safety of VALTREX have not been established in immunocompromised patients other than for the suppression of genital herpes in HIV-1–infected patients.” (opens the source at this quote in a new tab)

Famciclovir: labeled HSV indication in HIV infection and limitation in other immunocompromised patients

“FAMVIR is indicated for the treatment of recurrent episodes of orolabial or genital herpes in HIV-infected adults.” (opens the source at this quote in a new tab)
“The recommended dosage of FAMVIR for the treatment of recurrent orolabial or genital herpes in HIV-infected patients is 500 mg twice daily for 7 days.” (opens the source at this quote in a new tab)
“Immunocompromised patients other than for the treatment of recurrent orolabial or genital herpes in HIV-infected patients” (opens the source at this quote in a new tab)

Cross-resistance among acyclovir, valacyclovir, and famciclovir

“All acyclovir-resistant strains are also resistant to valacyclovir, and the majority are resistant to famciclovir.” (opens the source at this quote in a new tab)

Regulatory status of each second-line agent in a review of transplant recipients

“FOS is the only FDA-approved medication for R/R HSV infections to date.” (opens the source at this quote in a new tab)
“The main advantage of HPI over the standard of care is the mechanism of action that does not confer cross-resistance with other anti-HSV agents.” (opens the source at this quote in a new tab)

Amenamevir: approvals in Japan

Field	Review report
Non-proprietary name	“Amenamevir”
Applicant	“Maruho Co., Ltd.”
Dosage form and strength	“Tablets: Each tablet contains 200 mg of Amenamevir.”
Indication	“Herpes zoster”
Dosage and administration	“The usual adult dosage is 400 mg of amenamevir administered orally once daily after a meal.”

“In Japan, amenamevir received marketing approval in 2017 for the indication of herpes zoster” (opens the source at this quote in a new tab)
“and in February 2023 for the treatment of RHS, with approval of patient-initiated therapy (PIT), where medication can be initiated at the patient's discretion, based on early symptoms” (opens the source at this quote in a new tab)

“Amenamevir (Figure 1) is so far the only marketed HPI with antiviral activity against HSV1/2 and VZV and was approved in Japan in 2017 for the treatment of shingles” (opens the source at this quote in a new tab)

Amenamevir: phase 3 trial in recurrent genital herpes in immunocompetent adults

“In this phase 3 study, adult immunocompetent patients with recurrent genital herpes and able to accurately recognize prodromal symptoms were randomly assigned to administer amenamevir 1200 mg or placebo as a patient-initiated therapy within 6 hours after onset of prodromal symptoms.” (opens the source at this quote in a new tab)
“In the modified intention-to-treat population, which excluded patients with aborted lesions (amenamevir, n = 89; placebo, n = 97), the median time to all lesion healing was 4.0 days for amenamevir versus 5.1 days for placebo (hazard ratio, 1.60 [95% confidence interval, 1.19–2.15]; P = .0018), indicating superiority of amenamevir.” (opens the source at this quote in a new tab)

Amenamevir: phase 3 trial in recurrent herpes labialis in immunocompetent adults

“The modified intention-to-treat population, which excluded patients with aborted lesions, comprised 298 patients who self-initiated amenamevir and 307 who took placebo.” (opens the source at this quote in a new tab)
“the median time to all lesion healing was 5.1 days for amenamevir versus 5.5 days for placebo (hazard ratio, 1.24; 95% confidence interval, 1.06-1.46; p = 0.0085).” (opens the source at this quote in a new tab)

Amenamevir: case reports in acyclovir-resistant HSV after transplantation

“The treatment dosage of acyclovir (ACV), ganciclovir, and vidarabine ointment was not effective due to ACV-resistant mutations of the herpes simplex virus type 1 (HSV-1) in the thymidine kinase domain.” (opens the source at this quote in a new tab)
“Foscarnet is expected to be effective against ACV-resistant HSV-1 infection. However, it could not be used because the patient developed renal dysfunction.” (opens the source at this quote in a new tab)
“Nevertheless, amenamevir, a helicase-primase complex inhibitor, was effective in our patient who was significantly immunocompromised after allogeneic hematopoietic stem cell transplantation (allo-HSCT).” (opens the source at this quote in a new tab)

“A recent report detailed two patients with acute myeloid leukaemia post HCT who had R/R ACV HSV-1 infections. Both patients experienced FOS-related renal toxicity and were successfully treated with amenamevir with no apparent adverse events” (opens the source at this quote in a new tab)

“in people living with HIV with acyclovir-resistant genital HSV2, where amenamevir treatment was associated with clinical improvement of refractory lesions” (opens the source at this quote in a new tab)

Amenamevir: central nervous system complications reported during herpes zoster treatment

“Four cases of VZV meningitis or myelitis occurred following amenamevir treatment for herpes zoster dermatitis, all confirmed by PCR detection of VZV DNA in cerebrospinal fluid.” (opens the source at this quote in a new tab)
“These findings suggest that amenamevir alone may be insufficient to prevent VZV CNS infection in high-risk patients, highlighting the potential benefit of combination therapy” (opens the source at this quote in a new tab)

Brincidofovir: labeled indication and boxed warning

“TEMBEXA® is indicated for the treatment of human smallpox disease caused by variola virus in adult and pediatric patients, including neonates.” (opens the source at this quote in a new tab)
“TEMBEXA is not indicated for the treatment of diseases other than human smallpox disease” (opens the source at this quote in a new tab)
“An increased incidence of mortality was seen in TEMBEXA-treated subjects compared to placebo-treated subjects in a 24-week clinical trial when TEMBEXA was evaluated in another disease” (opens the source at this quote in a new tab)

Brincidofovir: reports of use in acyclovir-resistant HSV

“We report a child with myelodysplastic syndrome undergoing multiple SCT, who experienced HSV-1 disease including severe mucositis and herpetic whitlow, as well as high viral load AdV DNAemia. Both ACV and CDV were ineffective; however, viral loads were decreased with brincidofovir, resulting in viral clearance.” (opens the source at this quote in a new tab)

“One patient was treated for acyclovir-resistant HSV and one for disseminated VZV. There were 2 breakthrough cases of HSV infection during 2,170 patient days.” (opens the source at this quote in a new tab)
“The overall rate of breakthrough HSV infection was 1.0 per 1,000 patient-days, without any breakthrough VZV infections.” (opens the source at this quote in a new tab)

“Two case reports described using oral brincidofovir to treat R/R HSV infections in patients with haematological malignancies with good responses” (opens the source at this quote in a new tab)
“Of note, the oral formulation of brincidofovir is no longer under investigation because of its association with significant gastrointestinal toxicity in HCT recipients, as reported in clinical trials for cytomegalovirus prophylaxis” (opens the source at this quote in a new tab)

Brincidofovir: registered phase 3 trial of the intravenous formulation in adenovirus infection

Field	Registry record
Official title	“A Phase 3, Multicenter, Prospective, Randomized, Open-label Efficacy and Safety Study of Intravenous Brincidofovir Versus Intravenous Cidofovir for Treatment of Adenovirus Infection in Pediatric and Adult Subjects After Allogeneic Hematopoietic Cell Transplantation (Allo-HCT)”
Condition	“Adenovirus Infections”
Sponsor	“SymBio Pharmaceuticals”
Estimated enrollment	“180”

Helicase-primase inhibitors as a class: review statements

“Rescue therapies such as foscarnet exhibit limiting toxicity.” (opens the source at this quote in a new tab)
“Gene therapy is still in its early stages, while novel drugs such as helicase primase inhibitors (HPIs) are emerging as a promising alternative, showing high efficacy and the potential to overcome resistance.” (opens the source at this quote in a new tab)

“With amenamevir already approved for the treatment of VZV and HSV in Japan and with pritelivir’s granted breakthrough therapy designation and priority review for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, other companies have also expressed interest in small-molecule helicase-primase inhibitors (HPIs).” (opens the source at this quote in a new tab)
“Notably, HPIs retain activity against nucleoside-resistant isolates, highlighting a key advantage over nucleoside analogues.” (opens the source at this quote in a new tab)

Helicase-primase inhibitors: dosing regimens compared in a review

“Consequently, amenamevir is dosed at 1200 mg as a single dose or 400 mg daily, while pritelivir is dosed at a 400 mg loading dose followed by 100 mg daily doses. ABI-1179 is dosed 20–50 mg weekly in a phase 1b trial, and finally, ABI-5366 is dosed 350 mg weekly.” (opens the source at this quote in a new tab)

Helicase-primase inhibitors: limitations of the class stated in a review

“First, the extent to which currently available HPIs can meaningfully impact latent reservoirs (beyond suppressing reactivation) is unknown, and the clinical endpoints used so far (shedding and lesion rates) do not directly address cure.” (opens the source at this quote in a new tab)
“Second, tissue distribution constraints may still limit utility in severe manifestations where high CNS exposure is required.” (opens the source at this quote in a new tab)

Author interests declared in the two helicase-primase inhibitor reviews

“Alexander Birkmann is an employee of AiCuris, the company that develops pritelivir. Rob Saunders is a contractor (medical writer) for AiCuris.” (opens the source at this quote in a new tab)

“Both authors are named inventors on several patent families covering helicase-primase inhibitor adibelivir (IM-250). C. Gege is consultant and G. Kleymann founding CEO, employee and shareholder of Innovative Molecules GmbH.” (opens the source at this quote in a new tab)

ABI-5366 (GS-5366): registered phase 1a/1b trial

Field	Registry record
Official title	“A Phase 1a/1b, Blinded, Placebo-Controlled Study of the Safety, Tolerability and Pharmacokinetics of Single- and Multiple-Ascending Doses of ABI-5366 in Healthy Subjects and in Subjects Who Are Seropositive for Herpes Simplex Virus Type 2 With Recurrent Genital Herpes”
Condition	“Recurrent Genital Herpes Simplex Type 2”
Sponsor	“Assembly Biosciences”
Actual enrollment	“115”
Study completion	“2026-02-03”

ABI-5366 (GS-5366): phase 1 findings summarized in a review

“In Phase Ib, weekly oral regimens with 30 mg (+150 mg loading dose) or 350 mg administered to HSV2-seropositive patients with recurrent genital herpes for 29 days were also safe and well tolerated.” (opens the source at this quote in a new tab)
“The PK profile supports once-weekly dosing, with potential for once-monthly use.” (opens the source at this quote in a new tab)
“Robust antiviral activity was only observed at the 350 mg weekly dose, including a 94% reduction in HSV2 shedding rate (p < 0.01)” (opens the source at this quote in a new tab)
“Phase 2 study planning is in progress, with study initiation anticipated by the end of 2026” (opens the source at this quote in a new tab)

ABI-1179 (GS-1179): registered phase 1a/1b trial

Field	Registry record
Official title	“A Phase 1a/1b, Blinded, Placebo-Controlled Study of the Safety, Tolerability and Pharmacokinetics of Single- and Multiple Ascending Doses of ABI-1179 in Healthy Subjects and in Subjects Who Are Seropositive for Herpes Simplex Virus Type 2 With Recurrent Genital Herpes”
Condition	“Recurrent Genital Herpes Simplex Type 2”
Sponsor	“Assembly Biosciences”
Actual enrollment	“103”
Study completion	“2026-01-19”

ABI-1179 (GS-1179): phase 1 findings summarized in a review

“In December 2025, Assembly Biosciences reported positive interim Phase 1b results for ABI-1179 in participants with recurrent genital herpes caused by HSV2. A weekly oral dose of 50 mg showed very strong antiviral activity, including a 98% reduction in HSV2 viral shedding, more than a 99% reduction in high viral load shedding and a 91% reduction in virologically confirmed genital lesion rates compared with placebo.” (opens the source at this quote in a new tab)
“WO2026/015762 describes a novel method for using ABI-1179 to treat HSV infections that do not respond to one or more initial antiviral therapies (preferably acyclovir or pritelivir) due to one or more mutations, preferably in the UL5 gene” (opens the source at this quote in a new tab)

ABI-5366 and ABI-1179: license to Gilead and development status

“Successfully licensed helicase-primase inhibitor program for recurrent genital herpes to Gilead, including candidates ABI-5366 and ABI-1179, following positive Phase 1b interim data; development plan anticipated by mid-2026” (opens the source at this quote in a new tab)
“Completed dosing and follow-up for all participants in Phase 1a/b studies for ABI-5366 and ABI-1179” (opens the source at this quote in a new tab)
“ABI-5366, ABI-1179, ABI-6250 and ABI-4334 are investigational product candidates that have not been approved anywhere globally, and their safety and efficacy have not been established.” (opens the source at this quote in a new tab)

Adibelivir (IM-250): registered phase 1 trial

Field	Registry record
Official title	“Phase I Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Doses of IM-250 in Healthy Volunteers”
Condition	“Herpes Simplex Virus”
Sponsor	“Innovative Molecules GmbH”
Actual enrollment	“18”
Study completion	“2024-05-28”

Adibelivir (IM-250): phase 2a trial in recurrent genital herpes

“today announced that the first patient has been dosed in its Phase 2a clinical trial evaluating adibelivir (IM-250) for the treatment of recurrent genital herpes.” (opens the source at this quote in a new tab)
“The Phase 2a study is designed to evaluate the safety, antiviral activity, pharmacokinetics, and clinical efficacy of adibelivir in patients with recurrent genital herpes.” (opens the source at this quote in a new tab)

“An ongoing Phase 1b/2a study (EUCT 2024-516368-27–00), initiated in January 2025, is evaluating a 50, 100, and 200 mg weekly dose with HSV shedding as the primary endpoint, with completion expected early 2027” (opens the source at this quote in a new tab)
“In parallel, a strategic partnership with Alfasigma has secured global rights to a parenteral formulation of adibelivir for the treatment of herpes simplex encephalitis, highlighting its potential for severe and life-threatening infections” (opens the source at this quote in a new tab)

HDIT101 monoclonal antibody: registered phase 2 trial in recurrent anogenital HSV-2 infection

Field	Registry record
Official title	“A Randomized, Double-Blind, Double-Dummy Phase II Study of Single Dose HDIT101 Versus Standard of Care Valaciclovir in Patients With Chronic Recurrent Anogenital HSV-2 Infection”
Sponsor	“Heidelberg ImmunoTherapeutics GmbH”
Actual enrollment	“122”
Primary completion	“2021-08-25”

HDIT101 monoclonal antibody: registered phase 2 trial of the topical formulation in orolabial HSV-1 infection

Field	Registry record
Official title	“A Randomised, Double-Blind Phase II Trial of Topical HDIT101 Versus Placebo in Patients With Chronic Recurrent HSV-1 Infection and Orolabial Lesion”
Sponsor	“Heidelberg ImmunoTherapeutics GmbH”
Status and reason	“Terminated stopped for futility in interim analysis”
Primary completion	“2023-05-31”

UB-621 monoclonal antibody: registered phase 2 trial in recurrent genital HSV-2 infection

Field	Registry record
Official title	“A Randomized, Single-blind, Placebo-control, Parallel, Phase II Trial to Evaluate the Safety and Efficacy of UB-621 in Adults With Recurrent Genital HSV-2 Infection”
Sponsor	“UBP Greater China (Shanghai) Co., Ltd”
Estimated enrollment	“200”
Estimated primary completion	“2025-12”