Amenalief (amenamevir) / Maruho - LARVOL DELTA

Pathophysiology and treatment of acyclovir-resistant herpes simplex virus keratitis (PubMed, J Fr Ophtalmol) - "Herpetic keratitis (HK) caused by herpes simplex virus 1 (HSV-1) is the major cause of infection-related blindness in developed countries. Amenamevir (AMNV), a new drug targeting the viral helicase-primase (HP) enzyme complex, with proven efficacy for treatment of herpetic infections of other sites, has recently shown value in the management of ACV-resistant HK. Its TK-independent mechanism allows it to retain its antiviral activity even in cases of patient resistance to ACV."

Journal • Review • Herpes Simplex • Infectious Disease • Keratitis • Ocular Inflammation • Ophthalmology

Single Amino Acid Substitution Within the Helicase of Varicella Zoster Virus Makes It Resistant to Amenamevir. (PubMed, J Med Virol) - "We observed that the drug-resistant virus and the ORF55 K350N recombinant virus have high resistance to amenamevir, as the EC50 values in a plaque reduction assay were > 100 μM, while the two viruses remained susceptible to the nucleoside analog drug acyclovir. We observed that the single amino-acid substitution in the helicase induces amenamevir resistance, confirming the importance of the helicase in amenamevir's inhibition of virus growth. Our findings highlight the importance of regulating the clinical use of amenamevir to minimize the risk of the emergence of helicase K350N mutation, especially in the long-term use of amenamevir by immunosuppressed patients."

Journal • Herpes Zoster • Melanoma • Oncology • Solid Tumor • Varicella Zoster

Disproportionality Analysis of Amenamevir-Induced Encephalopathy Using the Japanese Adverse Drug Event Report Database 1. (PubMed, J Infect Chemother) - "These results suggest that amenamevir treatment may be associated with encephalopathy, particularly in patients aged ≥70 years. Healthcare providers should be aware of this potential risk, especially in elderly patients, to prevent severe central nervous system complications."

Adverse events • Journal • Chronic Kidney Disease • CNS Disorders • Cognitive Disorders • Herpes Zoster • Nephrology • Renal Disease • Varicella Zoster

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

HerpesDRG: a comprehensive resource for human herpesvirus antiviral drug resistance genotyping. (PubMed, BMC Bioinformatics) - "The database is released along with an R package that provides a simple approach to resistance variant annotation and clinical implication analysis from common sanger and next generation sequencing data. This represents the first openly available and community maintainable database of drug resistance mutations for the human herpesviruses (HHV), developed for the community of researchers and clinicians tackling HHV drug resistance."

Journal • Epstein-Barr Virus Infections

Convenient screening of the reproductive toxicity of favipiravir and antiviral drugs in Caenorhabditis elegans. (PubMed, Heliyon) - "Favipiravir, ribavirin, molnupiravir (NHC), acyclovir, ganciclovir, zidovudine, and thalidomide significantly increased the incidence of arrested embryos but amenamevir, letermovir, and guanosine did not. The concordance between the results of the screening system for reproductive toxicity of antivirals in C. elegans and those in experimental animals based on the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, reproductive toxicology confirms its appropriateness as a screening system for reproductive toxicity. Favipiravir and zidovudine were the least toxic to C. e legans among the antiviral drugs examined."

Journal • Infectious Disease • TERT

An exploratory study of the efficacy and safety of amenamevir for the treatment of herpes zoster in patients receiving immunosuppressive drugs. (PubMed, J Dermatol) - "Amenamevir is an oral once-daily antiherpesvirus drug that can be administered without dose adjustment in patients with impaired renal function. However, as worsening can happen around day 7, it is necessary to carefully monitor such patients and switch to other therapies such as intravenous acyclovir if necessary. Clinical trial identifier: Japan Registry of Clinical Trials jRCTs031190208."

Journal • Cardiovascular • Dermatology • Heart Failure • Hematological Disorders • Herpes Zoster • Immunology • Infectious Disease • Oncology • Pain • Solid Tumor • Varicella Zoster

Successful treatment of acyclovir-resistant herpes simplex virus infection with amenamevir in a patient who received umbilical cord blood transplantation for T-cell prolymphocytic leukemia. (PubMed, EJHaem) - "A 34-year-old woman received umbilical cord blood transplantation for refractory T-cell prolymphocytic leukemia after salvage therapy with alemtuzumab...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. Foscarnet is expected to be effective against ACV-resistant HSV-1 infection...To date, there is no established treatment against ACV-resistant HSV infection. This case report showed that amenamevir could be a promising treatment option for ACV-resistant HSV infection in patients with renal failure after allo-HSCT."

Journal • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Herpes Simplex • Immunology • Infectious Disease • Leukemia • Nephrology • Oncology • Prolymphocytic Leukemia • Transplantation

Efficacy and Safety of Amenamevir, a Helicase-Primase Inhibitor for the Treatment of Acyclovir-Resistant Herpes Simplex Virus 1 Keratitis. (PubMed, Cornea) - "Although there was no control group, AMNV may be a valuable option to reduce ACVR HSK recurrences."

Journal • Herpes Simplex • Keratitis • Ocular Inflammation • Ophthalmology

Replacement of sulfonamide by sulfoximine within a helicase-primase inhibitor with restricted flexibility. (PubMed, Bioorg Med Chem Lett) - "Since amenamevir is already approved for varicella-zoster virus (VZV) and HSV in Japan and pritelivir has received breakthrough therapy status for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, the target has sparked interest in me-too approaches. Here, we describe the attempt to improve nervous tissue penetration in Phaeno Therapeutics drug candidate HN0037 to target the latent reservoir of HSV by installing less polar moieties, mainly a difluorophenyl instead of a pyridyl group, and replacing the primary sulfonamide with a methyl sulfoximine moiety. However, all obtained stereoisomers exhibited a weaker inhibitory activity on HSV-1 and HSV-2."

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

Amenamevir for Treating Acyclovir-Resistant or Refractory Herpes Simplex Virus Infection in Allogeneic Hematopoietic Stem Cell Transplantation Recipients. Two Case Reports. (PubMed, Int J Antimicrob Agents) - No abstract available

Journal • Bone Marrow Transplantation • Herpes Simplex • Infectious Disease • Transplantation

Segmental cutaneous leukocytoclastic vasculitis associated with herpes zoster: a case report and literature review. (PubMed, Dermatol Reports) - "In support of this, histopathology in our case showed a C3-positive reaction with the small vessel walls in the dermis in direct immunofluorescence. Although the mechanism of LCV associated with herpes zoster remains unclear, we should consider LCV while diagnosing and treating patients with herpes zoster, especially immunosuppressed patients."

Journal • Review • Giant Cell Arteritis • Herpes Zoster • Infectious Disease • Varicella Zoster • Vasculitis

Real-world safety and efficacy of amenamevir in patients with herpes zoster in Japan: A postmarketing observational study (REWARD). (PubMed, J Dermatol) - "Factors affecting the time to pain resolution were the severity of cutaneous lesions and pain at the start of AMNV treatment and older age. This study demonstrated that the AMNV is safe and effective in patients with herpes zoster in a real-world clinical setting."

Journal • Observational data • P4 data • Real-world • Real-world evidence • Cardiovascular • Heart Failure • Hematological Disorders • Herpes Zoster • Nephrology • Pain • Renal Disease • Thrombocytopenia • Varicella Zoster

A Systematic Review of Second-Line Treatments in Antiviral Resistant Strains of HSV-1, HSV-2, and VZV. (PubMed, Cureus) - "Of the papers reviewed, nectin in 2.19% of the reviews had efficacy as a second-line treatments in HSV, amenamevir in 2.19%, methanol extract in 2.19%, monoclonal antibodies in 1.46%, arbidol in 1.46%, siRNA swarms in 1.46%, Cucumis melo sulfated pectin in 1.46%, and components from Olea europeae in 1.46%. In addition to this griffithsin in 1.46% was effective, Morus alba L. in 1.46%, using nucleosides in 1.46%, botryosphaeran in 1.46%, monoterpenes in 1.46%, almond skin extracts in 1.46%, bortezomib in 1.46%, flavonoid compounds in 1.46%, andessential oils were effective in 1.46%, but not effective in 0.73%...All patients, whether they are immunocompromised or not, deserve to have their infections clinically managed in a manner supported by comprehensive research. This review provides necessary information about treatment options for patients with resistant HSV infections and their providers."

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

Recent advance in management of herpes simplex in Japan. (PubMed, J Dermatol) - "Amenamevir, an inhibitor of viral helicase primase, is available in Japan and labeled in addition to herpes zoster. These new diagnostic and therapeutic tools should be used for better management of herpes simplex."

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

Current scenario and future applicability of antivirals against herpes zoster. (PubMed, Korean J Pain) - "However, limited antivirals are only licensed clinically for the treatment of HZ, including acyclovir, valacyclovir, famciclovir, brivudine, and amenamevir. Fortunately, some new antivirals against different types of Herpesviridae have been investigated and suggested as novel drugs against VZV. Therefore, this review focuses on discussing the difference in efficacy and safety in the currently licensed antivirals for the treatment of HZ, the applicability of future novel antivirals against VZV, and the preventive or therapeutic effects of these antivirals on ZAP or PHN."

Journal • Review • Herpes Zoster • Immunology • Infectious Disease • Neuralgia • Pain • Varicella Zoster

Recent topics in the management of herpes zoster. (PubMed, J Dermatol) - "In 2016, the varicella vaccine was expanded to include prevention of herpes zoster, and a new subunit vaccine was also launched in 2020. In recent years, anti-herpesvirus drugs with novel pharmacological effects have also been introduced, and the environment surrounding the treatment of herpes zoster is entering a new era."

Journal • Review • Herpes Zoster • Varicella Zoster

Adverse effects of cytochrome P450 induction by amenamevir in an elderly man with herpes zoster. (PubMed, Psychogeriatrics) - No abstract available

Adverse events • Journal • Herpes Zoster • Varicella Zoster

A phase 3, randomized, double-blind, placebo-controlled study evaluating a single, patient-initiated dose of amenamevir for recurrent herpes labialis. (PubMed, J Dermatol) - "Treatment-emergent adverse events in both groups were generally mild in severity; there were two moderate events that were judged unrelated to study treatment, and no severe or serious events. In summary, a single patient-initiated dose of amenamevir 1200 mg taken within 6 hours of prodromal symptom onset significantly shortened the time to all lesion healing of recurrent herpes labialis compared with placebo, with no clinically important safety concerns."

Clinical • Journal • P3 data • Herpes Simplex • Pain

Single-Dose, Patient-Initiated Amenamevir Therapy for Recurrent Genital Herpes: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study. (PubMed, Open Forum Infect Dis) - "Clinical Trials Registration. JapicCTI-194955."

Clinical • Journal • P3 data • Herpes Simplex • Infectious Disease

Which self-etch acidic composition may result in higher dental bonds at the long-term? A network meta-analysis review of in vitro studies. (PubMed, J Dent) - "The acidic composition of SE adhesives affects the resistance of dental bonds after simulated aging, with 10-MDP playing a significant role in the adhesion to dentin but not to the enamel."

Journal • Preclinical • Retrospective data • Review

Helicase-primase inhibitors from Medshine Discovery Inc. (WO2018/127207 and WO2020/007355) for the treatment of herpes simplex virus infections - structure proposal for Phaeno Therapeutics drug candidate HN0037. (PubMed, Expert Opin Ther Pat) - "With amenamevir already approved for varicella-zoster virus and with pritelivir's granted breakthrough therapy designation for the treatment of acyclovir-resistant HSV infections in immunocompromised patients, the target has sparked interest for me-too approaches. We describe the opportunities and limitations of the helicase-primase inhibitor patent portfolio from Phaeno Therapeutics and propose the structure of their drug candidate HN0037, which has been licensed from Medshine Discovery."

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

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A 1-Year Survey of Zoster-Associated Pain after Amenamevir Treatment. (PubMed, Dermatol Ther (Heidelb)) - "Although conclusions must remain tentative without further comparative studies, amenamevir seems to have a similar effect on PHN as conventional nucleoside analogs, despite having a different action mechanism."

Journal • Herpes Zoster • Neuralgia • Pain • Varicella Zoster

Aseptic Meningitis after Amenamevir Treatment for Herpes Zoster in the First Branch of the Trigeminal Nerve: A Case Report. (PubMed, Intern Med) - "Patients with CNS complications often have skin rashes near the trigeminal region. Thus, we should be alert for signs of CNS infection when administering amenamevir to patients with such rashes."

Journal • CNS Disorders • Dermatology • Herpes Zoster • Infectious Disease • Varicella Zoster