pritelivir (AIC316) / AiCuris - LARVOL DELTA

PRIOH-1: Trial on Efficacy and Safety of Pritelivir Tablets for Treatment of Acyclovir-resistant Mucocutaneous HSV (Herpes Simplex Virus) Infections in Immunocompromised Subjects (clinicaltrials.gov) - P3 | N=158 | Completed | Sponsor: AiCuris Anti-infective Cures AG | Active, not recruiting ➔ Completed

Trial completion • Herpes Simplex • Infectious Disease

Next Generation 3D Printed Multipurpose Intravaginal Ring For Sustained Co-Delivery of Antiretroviral Drugs and A Contraceptive Hormone. (PubMed, Pharm Res) - "Collectively, these results demonstrate that this first-in-line 3D printed MPT IVR has potential to expand preventative choices for young women and girls against HIV, HSV, and unplanned pregnancy."

Journal • Human Immunodeficiency Virus • Infectious Disease

Structural basis of herpesvirus helicase-primase inhibition by pritelivir and amenamevir. (PubMed, Sci Adv) - "The structures reveal a bilobed architecture highlighting HP coordinated action at the replication fork and providing a structural basis for HP inhibition by illustrating precisely how pritelivir and amenamevir block helicase activity. Data lay a solid foundation for the development of improved antiviral therapies."

Journal • Herpes Simplex • Infectious Disease • RPL11

Structural and mechanistic insights into herpesvirus helicase-primase and its therapeutic inhibitors. (PubMed, Nat Microbiol) - "Here we present the cryogenic electron microscopy structure of the HSV-1 HP apo-complex (3.8 Å), along with structures bound to pritelivir (3.2 Å) and amenamevir (3.2 Å)-two clinically active, chemically distinct HPIs. The potency of both inhibitors against HSV variants bearing mutations within the HPI binding pocket supports the high-resolution mapping of key molecular interactions while revealing residues that govern their antiviral spectrum against alphaherpesviruses. Our results provide important insight into the unique architecture of the HP complex and the mechanism of inhibition of HPIs, paving the way for the development of next-generation antivirals to treat herpesvirus infections."

Journal • Herpes Simplex • Infectious Disease

Discovery of a Baloxavir-Inspired Endonuclease Inhibitor That Prevents Herpes Simplex Virus 1 Replication in Cell Culture and In Vivo. (PubMed, Adv Sci (Weinh)) - "Acyclovir and other viral DNA polymerase inhibitors are effective antiviral agents for treating HSV infections. However, despite the recent approval of pritelivir and amenamevir (helicase-primase complex inhibitors), drug resistance is still a major threat to therapeutic success...LN-7 demonstrates antiviral efficacy in infected mice, while exhibiting fewer clinical signs compared to controls. Overall, LN-7 emerges as a promising lead for treating herpesvirus infections and is therefore a first-in-class drug candidate targeting HSV genome packaging."

Journal • Preclinical • Herpes Simplex • Infectious Disease

Added-value of high-throughput sequencing for early detection of HSV-2 resistant subpopulations in the helicase-primase inhibitors era: A case report. (PubMed, Int J Antimicrob Agents) - "Immunocompromised patients are at high risk of developing acyclovir-resistant (ACV) herpes simplex virus (HSV) infections. Helicase-primase inhibitors, including pritelivir (PTV), represent an antiviral option to nephrotoxic alternatives...HTS technologies enhance sensitivity over conventional methods and provide valuable insights for managing antiviral resistance. Continuous monitoring and research to elucidate the functional impact of specific mutations of unknown significance on drug resistance are essential for building robust HSV resistance databases."

Journal • Herpes Simplex • Infectious Disease

Structural determinants of nervous system exposure of adibelivir (IM-250) and related herpes helicase-primase inhibitors across animal species. (PubMed, Antiviral Res) - "In diverse animal species, after single or multiple doses of helicase-primase drugs by oral or intravenous administration, only adibelivir (IM-250) achieved concentrations in the nervous system in the range of plasma or blood levels (ratio 0.5 to 4 nervous system/plasma), while other helicase-primase inhibitors with distinct structures, including amenamevir, pritelivir or ABI-5366, showed a low brain/plasma ratio of less than 0.1. In preclinical studies published so far, adibelivir was efficacious in the herpes encephalitis and neonatal animal model and reduced the reactivation competence of the neuronal latent herpes viral reservoir. Ongoing clinical trials with HPIs will show whether sufficient drug exposure in brain and ganglia will translate into more effective herpes therapies for patients."

Journal • CNS Disorders • Herpes Simplex • Infectious Disease • Keratitis • Ocular Inflammation • Ophthalmology

Efficacy and safety results from the Phase 2 clinical trial of pritelivir versus foscarnet for treatment of acyclovir-refractory and/or resistant mucocutaneous HSV infections in immunocompromised subjects (IDWeek 2025) - No abstract available

Clinical • P2 data • Herpes Simplex • Infectious Disease

Pritelivir, a nonnucleoside helicase-primase inhibitor, for the treatment of herpes simplex virus (HSV) infections in Phase 3 clinical development. (IDWeek 2025) - No abstract available

Clinical • P3 data • Herpes Simplex • Infectious Disease

PRIOH-1: Trial on Efficacy and Safety of Pritelivir Tablets for Treatment of Acyclovir-resistant Mucocutaneous HSV (Herpes Simplex Virus) Infections in Immunocompromised Subjects (clinicaltrials.gov) - P3 | N=153 | Active, not recruiting | Sponsor: AiCuris Anti-infective Cures AG | Recruiting ➔ Active, not recruiting

Enrollment closed • Herpes Simplex • Infectious Disease

Evaluation of the patent portfolio for helicase-primase inhibitor ABI-5366 of Assembly biosciences inc. (PubMed, Expert Opin Ther Pat) - P1 | "With amenamevir already approved for varicella-zoster virus and herpes simplex in Japan and with pritelivir's granted breakthrough therapy designation for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, the target has sparked interest in helicase-primase inhibitors...This me-too approach on the old Bayer urea series is currently in clinical phase I (NCT06385327) and the modification is the bridging of the two urea nitrogens via an alkylene linkage. The chemical structure for 1,3-disubstituted tetrahydropyrimidin-2(1 H)-one derivative ABI-5366 is presented and its potential opportunities and limitations as a long-acting oral administration or injectable depot drug compared to other HPIs are discussed."

Journal • Herpes Simplex • Herpes Zoster • Infectious Disease • Varicella Zoster

Pritelivir for the Treatment of Nucleoside Analogue-Resistant Orolabial Herpes Simplex Virus 2 in a Person Living with HIV. (PubMed, J Assoc Med Microbiol Infect Dis Can) - "The patient received multiple treatment courses including nucleoside analogue therapy, topical and intravenous foscarnet and cidofovir, and topical imiquimod but these failed to establish a significant and durable therapeutic response...Subsequent genotyping revealed a M183X mutation in UL23 expected to convey resistance to acyclovir and penciclovir...Pritelivir is a novel helicase-primase inhibitor that appears to be an attractive option for management of resistant herpes simplex infections due to its unique mechanism, excellent oral bioavailability, and minimal toxicity. To our knowledge, this is the first described case of treatment of nucleoside analogue-resistant orolabial herpes simplex 2 infection with pritelivir and the first documented use of pritelivir in Canada."

Journal • Herpes Simplex • Human Immunodeficiency Virus • Infectious Disease

Structural Basis of Herpesvirus Helicase-Primase Inhibition by Pritelivir and Amenamevir. (PubMed, bioRxiv) - "The structures reveal a bilobed architecture highlighting helicase-primase coordinated action at the replication fork and providing a structural basis for HP inhibition by illustrating precisely how pritelivir and amenamevir block helicase activity. Data lays a solid foundation for the development of improved antiviral therapies."

Journal • Herpes Simplex • Infectious Disease • RPL11

Herpes Simplex Virus and Drug Resistance - Comprehensive Update on Resistance Mutations and Implications for Clinical Management: A Narrative Review. (PubMed, Clin Microbiol Infect) - "This dataset paves the way to harmonize reporting of DRMs for diagnostic labs and to accelerate genotypic DST interpretation through aggregated data. Ongoing large-scale data collection of genotypic, phenotypic, and clinical data is crucial for evidence-based management of HSV antiviral resistance and clinical guidelines."

Journal • Review • Epstein-Barr Virus Infections • Herpes Simplex • Infectious Disease

Bidirectional transfer of pritelivir across term human placenta and its effect on placental functions. (PubMed, J Pharmacol Exp Ther) - "Genital herpes in pregnancy is treated with nucleoside analog drugs such as acyclovir to reduce the risk of mother-to-neonate transfer of the virus. Although fetal exposure to the drug is plausible, pritelivir did not impact the viability and functionality of the placenta. Higher transplacental transfer of pritelivir in the fetal-to-maternal direction rather than maternal-to-fetal direction suggested the involvement of placental membrane transporters."

Journal • Breast Cancer • Herpes Simplex • Infectious Disease • Oncology • Solid Tumor

Successful treatment and secondary prophylaxis with pritelivir for a recurrent multi-drug resistant HSV-1 infection in an allogeneic hematopoietic stem cell transplant recipient. (PubMed, Clin Microbiol Infect) - No abstract available

Journal • Bone Marrow Transplantation • Infectious Disease • Transplantation

Treatment of herpes simplex encephalitis with the helicase-primase inhibitor pritelivir in an immunocompromised patient (ESCMID Global 2025) - No abstract available

Clinical • CNS Disorders • Herpes Simplex

How We Diagnose and Manage Refractory and Resistant Herpes Simplex Virus Mucocutaneous Infection After Hematopoietic Cell Transplantation. (PubMed, Clin Microbiol Infect) - "The proposed R/R HSV mucocutaneous infection diagnostic and treatment algorithm guides the appropriate management of these difficult-to-treat infections, potentially improving patient outcomes."

Journal • Review • Bone Marrow Transplantation • Herpes Simplex • Human Immunodeficiency Virus • Infectious Disease • Transplantation

Combined use of pritelivir with acyclovir or foscarnet suppresses evolution of HSV-1 drug resistance. (PubMed, Virus Evol) - "PFA + PTV dual treatment induced PFA resistance mutations in the DP, but PTV resistance mutations were not acquired, even after 15 passages. Our data suggest that combining the helicase-primase inhibitor PTV with a DP inhibitor may be an effective strategy to prevent drug resistance evolution in HSV-1."

Journal • Herpes Simplex • Infectious Disease

PRIOH-1: Trial on Efficacy and Safety of Pritelivir Tablets for Treatment of Acyclovir-resistant Mucocutaneous HSV (Herpes Simplex Virus) Infections in Immunocompromised Subjects (clinicaltrials.gov) - P3 | N=153 | Recruiting | Sponsor: AiCuris Anti-infective Cures AG | Trial completion date: Apr 2025 ➔ Nov 2025 | Trial primary completion date: Jan 2025 ➔ Jul 2025

Trial completion date • Trial primary completion date • Herpes Simplex • Infectious Disease

Next-generation 3D printed multipurpose prevention intravaginal ring for prevention of HIV, HSV-2, and unintended pregnancy. (PubMed, J Control Release) - "Anti-HIV drug (Dapivirine, DPV), anti-herpes drug (Pritelivir, PTV) and a contraceptive drug (Levonorgestrel, LNG) were loaded in a macaque size IVR (25 mm outer diameter, OD; 6.0 mm cross-section, CS) allometrically scaled from the human size (54 mm OD; 7.6 mm CS) IVR analogue...Additionally, MPT IVRs elicited no observed alterations in systemic CD4+ and CD8+ T cells during the entire study. Collectively, the proposed MPT IVR has potential to expand preventative choices for young women and girls against unintended pregnancy against two highly prevalent sexually transmitted infections (STIs)."

Journal • Herpes Simplex • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8 • CXCL8 • IFNG • IL10 • IL12A • IL17A • IL18 • IL1B • IL6 • TNFA

Effect of Renal and Hepatic Impairment on the Pharmacokinetics of Pritelivir and Its Metabolites. (PubMed, Clin Pharmacol Drug Dev) - "A modest effect of moderate hepatic impairment was observed for PPA and ATS. Pritelivir was safe and well tolerated in healthy subjects and subjects with renal or hepatic impairment."

Journal • PK/PD data • Hepatology • Renal Disease

Helicase-primase inhibitors for the treatment of herpes simplex virus infections - patent evaluation of WO2023/225162 from gilead sciences inc. (PubMed, Expert Opin Ther Pat) - "With amenamevir already approved for varicella-zoster virus and herpes simplex in Japan and with pritelivir's granted breakthrough therapy designation for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, the target has sparked interest in helicase-primase inhibitors (HPIs)...The asset was contributed to Assembly Biosciences, where it is under development as ABI-1179 at the investigational new drug (IND) enabling stage for high-recurrence genital herpes. A structure proposal for indolinoyl derivative ABI-1179 is presented, showing its potential opportunities and limitations compared to other HPIs."

Journal • Review • Herpes Simplex • Herpes Zoster • Infectious Disease • Varicella Zoster

Advances and Prospect in Herpesviruses infections after Hematopoietic Cell Transplantation: Closer to the Finish Line? (PubMed, Clin Microbiol Infect) - "While considerable advances have been achieved for the treatment and prevention of herpes virus infections, most notably with CMV, the coming years should hold additional opportunities to tame the beast in these herpesviruses post allogeneic HCT, with the advent of new antivirals, cell-mediated immunity testing, and cytotoxic T lymphocytes infusions."

Journal • Review • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Herpes Simplex • Herpes Zoster • Infectious Disease • Transplantation • Varicella Zoster

A Screening Study Identified Decitabine as an Inhibitor of Equid Herpesvirus 4 That Enhances the Innate Antiviral Response. (PubMed, Viruses) - "Aciclovir, the most widely used antiviral against alpha-herpesviruses in vivo, does not appear to be effective against EHV-4 in vitro. Potential antiviral activities were confirmed for eight molecules (idoxuridine, vidarabine, pritelivir, cidofovir, valganciclovir, ganciclovir, aphidicolin, and decitabine). Decitabine demonstrates the highest efficacy against EHV-4 in vitro. Transcriptomic analysis revealed the up-regulation of various genes implicated in interferon (IFN) response, suggesting that decitabine triggers the immune antiviral pathway."

Journal • Preclinical • CNS Disorders • Infectious Disease