pritelivir (AIC316) / AiCuris - LARVOL DELTA

Positive treatment response of pritelivir achieved in refractory HSV infections in immunocompromised patients, including haematopoietic stem cell and solid organ transplant recipients and oncology patients: PRIOH-1 phase III trial (ESCMID Global 2026) - No abstract available

Clinical • Late-breaking abstract • P3 data • Herpes Simplex • Infectious Disease • Solid Organ Transplantation • Transplantation

In vitro two-way drug–drug interaction study shows no antagonism or potentiation between post-phase III anti-HSV pritelivir and nine licensed anti-HIV drugs (INSTI, NNRTI, NRTI, and CAI) (ESCMID Global 2026) - No abstract available

P3 data • Preclinical • Human Immunodeficiency Virus • Infectious Disease

Pritelivir demonstrated superior lesion healing with extended treatment compared to investigator's choice for refractory herpes simplex virus infection in immunocompromised patients in the PRIOH-1 phase III trial (ESCMID Global 2026) - No abstract available

Clinical • P3 data • Herpes Simplex • Infectious Disease

ACICLOVIR-RESISTANT HERPES SIMPLEX VIRUS IN PEDIATRIC PATIENTS UNDERGOING ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANT: A CASE SERIES (EBMT 2026) - "All patients were treated with second-line antivirals (foscarnet and/or cidofovir), and three patients were treated with third-line antivirals (pritelivir). Aciclovir-resistant HSV infection in pediatric HSCT recipients is associated with high morbidity and mortality, limited therapeutic options, and significant treatment-related toxicity. Early recognition, resistance testing, timely initiation of second-line therapy and weaning of immunosuppression are critical for disease control. Emerging therapies, such as helicase-primase inhibitors and adoptive T-cell therapy, hold promise but remain limited by access and pediatric data."

Clinical • Bone Marrow Transplantation • Gastrointestinal Disorder • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Herpes Simplex • Immunology • Infectious Disease • Inflammation • Keratitis • Leukemia • Myelodysplastic Syndrome • Ocular Inflammation • Ophthalmology • Pediatrics • Pneumonia • Primary Immunodeficiency • Respiratory Diseases • Sickle Cell Disease • Transplantation • Transplantation Associated Thrombotic Microangiopathy

PRITELIVIR DEMONSTRATED SUPERIOR EFFICACY COMPARED TO INVESTIGATOR'S CHOICE TREATMENT FOR REFRACTORY HERPES SIMPLEX VIRUS INFECTIONS IN IMMUNOCOMPROMISED PATIENTS: PRIOH-1, PHASE 3 SAFETY AND EFFICACY (EBMT 2026) - P3 | " In this randomized (1:1), controlled, open label trial, 101 IC patients (≥16 years) with R±R HSV mucocutaneous infection received oral pritelivir (100 mg daily; 400 mg loading dose) or ICT (IV foscarnet, IV/topical cidofovir, or topical imiquimod) for up to 28 days, extendable to 42 days. Eligibility criteria included hematopoietic cell transplant, solid organ transplant, HIV, malignancy, or chronic use of immunosuppressive treatment with refractory/clinical failure (defined as no clinical improvement of lesions after ≥7 days of standard of care nucleoside analogue therapy or confirmed acyclovir resistance)... Pritelivir met the Phase 3 primary endpoint, demonstrating statistically superior efficacy compared with ICT, with a favorable safety and tolerability profile. These findings support pritelivir as a promising oral agent to address the unmet needs of refractory HSV infections in IC patients.Table 1 Incidence of TEAEs (≥ 10%): Pritelivir vs...."

Clinical • P3 data • Herpes Simplex • Human Immunodeficiency Virus • Immunology • Infectious Disease • Primary Immunodeficiency • Solid Organ Transplantation

Pritelivir Demonstrated Superior Efficacy Compared to Investigator's Choice Treatment for Refractory Herpes Simplex Virus Infections In Immunocompromised Patients: PRIOH-1, Phase 3 Safety and Efficacy (TCT-ASTCT-CIBMTR 2026) - "Methods In this randomized (1:1), controlled, open label trial, 101 IC patients (≥16 years) with R±R HSV mucocutaneous infection received oral pritelivir (100 mg daily; 400 mg loading dose) or ICT (IV foscarnet, IV/topical cidofovir, or topical imiquimod) for up to 28 days, extendable to 42 days. Eligibility criteria included hematopoietic cell transplant, solid organ transplant, HIV, malignancy, or chronic use of immunosuppressive treatment with refractory/clinical failure (defined as no clinical improvement of lesions after ≥7 days of standard of care nucleoside analogue therapy or confirmed acyclovir resistance)...Conclusions Pritelivir met the Phase 3 primary endpoint, demonstrating statistically superior efficacy compared with ICT, with a favorable safety and tolerability profile. These findings support pritelivir as a promising oral agent to address the unmet needs of refractory HSV infections in IC patients."

Clinical • Late-breaking abstract • P3 data • Herpes Simplex • Human Immunodeficiency Virus • Immunology • Infectious Disease • Primary Immunodeficiency • Solid Organ Transplantation

Acyclovir-Resistant Herpes Simplex Virus in Pediatric Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant: A Case Series. (PubMed, Transpl Infect Dis) - "Acyclovir-resistant HSV infection in pediatric HSCT recipients is associated with high morbidity and mortality, limited therapeutic options, and significant treatment-related nephrotoxicity. Early recognition, early resistance testing, prompt initiation of second-line therapy, and weaning of immunosuppression are critical. Emerging therapies, such as helicase-primase inhibitors and adoptive T-cell therapy, hold promise but remain limited by access and pediatric data."

Journal • Bone Marrow Transplantation • Gastrointestinal Disorder • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Herpes Simplex • Immunology • Infectious Disease • Keratitis • Leukemia • Myelodysplastic Syndrome • Ocular Inflammation • Oncology • Ophthalmology • Pediatrics • Pneumonia • Primary Immunodeficiency • Respiratory Diseases • Sickle Cell Disease • Transplantation

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