azvudine (FNC) / Granlen - LARVOL DELTA

Strain-promoted azide-alkyne cycloaddition-based fluorometric detection of azvudine using DBCO-functionalized carbon dots. (PubMed, Mikrochim Acta) - No abstract available

Journal

Azvudine potently inhibits African swine fever virus replication in vitro. (PubMed, Virus Res) - "Further mechanistic studies indicated that Azvudine acts at a post-entry stage of the viral life cycle and does not directly inactivate viral particles. These findings suggest that Azvudine is a promising repurposed candidate for anti-ASFV drug development."

Journal • Preclinical

Azvudine remodels the local immunosuppressive microenvironment and exhibits sustained anti-tumor effects in combination with anti-PD-1 therapies. (PubMed, Front Med) - "FNC remodels the TME by mitigating immunosuppression and amplifying anti-tumor immunity, offering a promising strategy to augment existing immunotherapies. Further clinical evaluation is warranted to ascertain the translational potential of FNC in diverse oncologic settings."

Journal • Oncology • CALR • CD8 • HMGB1

Impact of COVID-19 in Thalassemia Patients Undergoing Hematopoietic Stem Cell Transplant Recipients (ASH 2023) - "Of the seven patients treated with medications, four were azvudine and three were nematasvir... The low infection rate and no severe cases may be due to scientific protection and timely medication. There are no special risk factors for COVID-19 infection in thalassemia patients after transplantation."

Clinical • Bone Marrow Transplantation • Genetic Disorders • Graft versus Host Disease • Immunology • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Transplantation

Nirmatrelvir/Ritonavir Reduces Infection Duration in Hospitalized Hematological Malignancies Patients with Mild-to-Moderate COVID-19: A Retrospective Study (ASH 2024) - P=N/A | "Patients diagnosed with severe COVID-19, or treated with convalescent plasma, azvudine, or molnupiravir, or with unknown vaccination status, were excluded. Other treatment regimens did not achieve a statistically significant difference in time to viral clearance. Nirmatrelvir/ritonavir use within five days reduced the time to viral clearance (HR=1.51, 95% CI 1.01-2.23).ConclusionsNirmatrelvir/ritonavir use within five days in hospitalized HM patients with mild-to-moderate COVID-19 does not reduce mortality but shortens infection duration."

Retrospective data • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases

The efficacy of azvudine in treating hospitalized COVID-19 patients: a retrospective single-center cohort analysis. (PubMed, J Thorac Dis) - "The findings show that azvudine is effective in treating hospitalized COVID-19 patients. It could be considered for therapeutic use in this patient population."

Journal • Retrospective data • Critical care • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

In vitro comparison of the susceptibilities of the same drug resistance mutations to reverse-transcriptase inhibitors of subtype B and CRF01_AE HIV-1 strains. (PubMed, Sci Rep) - "However, phenotypic analysis of reconstructed clones containing these resistance mutations revealed that CRF01_AE exhibited significantly lower sensitivity to RTIs than did subtype B. For azvudine (FNC), a novel nucleoside reverse transcriptase inhibitor (NRTI), the resistance level of CRF01_AE was significantly lower than that of subtype B. In conclusion, the same mutation affecting resistance to RTIs can have significantly different impacts depending on the subtype of the HIV-1 strain. This finding serves as a reference for guiding rational drug use in the future. Moreover, relying solely on phenotypic experimental results from subtype B to evaluate resistance levels of unclear mutations in other subtypes may be inappropriate and should be approached with caution."

Clinical • Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease

Association of Azvudine with severe outcomes among hospitalized patients with COVID-19 during an omicron-dominance period in Wuhan, China: a single-center, retrospective, matched cohort study. (PubMed, BMC Infect Dis) - "During a SARS-CoV-2 Omicron variants predominant period, initiation of Azvudine could provide considerable protection against all-cause death, composite severe outcome measure, and result in a significantly shorter nucleic acid conversion time among hospitalized patients with COVID-19. A wider use of Azvudine in clinical settings should be considered."

Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Real-world efficacy of oral azvudine in hospitalized patients with COVID-19: A multicenter retrospective cohort study. (PubMed, J Infect Public Health) - "During the omicron epidemic in China, oral administration of azvudine was associated with a reduced risk of the composite outcome and all-cause mortality in COVID-19 patients."

Journal • Real-world evidence • Retrospective data • Critical care • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Real-World Evaluation Study of Azvudine for the Treatment of Patients With COVID-19: A Systematic Review and Meta-Analysis. (PubMed, Can J Infect Dis Med Microbiol) - "The incidence of AEs in the Azvudine group and the Nirmatrelvir/Ritonavir group was 4.13% (60/1453) and 5.08% (67/1319), respectively, indicating that Azvudine significantly reduced the incidence of AEs compared to Nirmatrelvir/Ritonavir (OR: 0.68, 95% CI: 0.47, 0.98). In terms of safety, Azvudine demonstrated a favorable safety profile (GRADE: moderate-certainty evidence because of suspected publication bias and residual confounding). Further large-scale studies are needed to validate its efficacy and safety."

HEOR • Journal • Real-world evidence • Retrospective data • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Mechanism and spectrum of inhibition of viral polymerases by 2'-deoxy-2'-β-fluoro-4'-azidocytidine or azvudine. (PubMed, NAR Mol Med) - "The therapeutic value of antiviral nucleoside analogs was highlighted during the coronavirus disease 2019 (COVID-19) pandemic, with remdesivir and molnupiravir repurposed for their broad-spectrum antiviral activity. Collectively, the data show that inhibition of viral polymerases by FNC-TP can translate to antiviral activity against both retroviruses and RNA viruses, but the link is not evident for SARS-CoV-2. FNC-TP is a poor substrate for SARS-CoV-2 RdRp, and FNC lacks significant antiviral activity against SARS-CoV-2 in cell culture."

Journal • Dengue Fever • Hepatitis C • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Factors Influencing COVID-19 Viral Clearance: Implications for Vaccination and Antiviral Therapy. (PubMed, Infect Drug Resist) - "Among these, patients vaccinated ≥360 days prior had shortest negative conversion time (5.6 days) and shortest hospitalization (10.3 days).Antiviral therapy with Nirmatrelvir-ritonavir (N/R) accelerated viral clearance more effectively than Azvudine (2.29 vs 1.82 Ct/day, p = 0.045) and no antiviral treatment (1.88 Ct/day, p = 0.041), Although NAT-treated patients achieved viral negativity more rapidly (6.2 days, p = 0.013), N/R demonstrated superior clearance rate. Viral clearance dynamics in hospitalized COVID-19 patients are influenced by age, comorbidities, vaccination, and antiviral treatment. Administration of ≥2 inactivated vaccine doses-especially ≥360 days apart-and early N/R therapy may accelerate viral clearance and reduce hospital stay."

Journal • Cardiovascular • Coronary Artery Disease • Heart Failure • Hypertension • Infectious Disease • Novel Coronavirus Disease

The effect of monotherapy versus combination antiviral therapy on all-cause mortality risk in COVID-19 patients. (PubMed, Diagn Microbiol Infect Dis) - "Therefore, Paxlovid alone reduced mortality risk in moderate and severe cases, while the combination therapy with two antiviral drugs also provided some protection. However, the type-specific impact of Azvudine treatment was notable, with mild cases experiencing significantly better survival rates."

Journal • Monotherapy • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Effectiveness and safety of azvudine in the treatment of COVID-19 patients: a retrospective cohort study using propensity score matching. (PubMed, Front Cell Infect Microbiol) - "One case of mild gastrointestinal discomfort was reported in the azvudine group. Azvudine significantly reduced hospitalization duration in mild-to-moderate COVID-19 patients with a favorable safety profile."

Journal • Retrospective data • Cough • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Impact of early and delayed azvudine administration on COVID-19 mortality: a retrospective study. (PubMed, Sci Rep) - "The study indicated that the benefit of azvudine seemed more significant within 8 days of symptoms onset and the administration of azvudine reduced the risk of death in adult COVID-19 patients. In the future, large randomized controlled trials (RCT) studies are needed to confirm our conclusions because of the inherent limitation of single-centre, retrospective study."

Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Real-world effectiveness and safety of oral azvudine versus Paxlovid in patients with COVID-19 and pre-existing hypertension: a multicentre, retrospective, cohort study in Henan Province, China. (PubMed, BMJ Open) - P | "Among COVID-19 patients with pre-existing hypertension, the effectiveness of azvudine is not inferior to Paxlovid in reducing all-cause death and composite disease progression, with fewer adverse events."

Clinical • Journal • Real-world evidence • Retrospective data • Cardiovascular • Hypertension • Infectious Disease • Novel Coronavirus Disease

Real-world data of Azvudine-induced hepatotoxicity among hospitalized COVID-19 patients in China: a retrospective case-control study. (PubMed, Front Pharmacol) - "The concomitant use of antivirals [OR: 3.80 (1.47-10.1), P = 0.006] and anticoagulant drugs [OR: 3.12 (1.77-5.61), P < 0.001], particularly Ganciclovir [OR: 4.11 (1.45-12.2), P = 0.008], Low-Molecular-Weight Heparin Calcium [OR: 3.00 (1.69-5.33), P < 0.001], and Enoxaparin [OR: 2.68 (0.99-7.10), P = 0.047], were significantly associated with an increased risk of hepatotoxicity. These findings underscored the importance of monitoring liver function during Azvudine treatment and caution against concomitant use of certain medications. Further research was warranted to elucidate the mechanisms underlying Azvudine-induced hepatotoxicity and optimize clinical management strategies."

Journal • Real-world evidence • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Azvudine Suppresses Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma by Targeting the Notch-HEY Signalling Pathway. (PubMed, Int J Mol Sci) - "To identify the primary target of FNC, microscale thermophoresis (MST) and molecular dynamics (MD) simulations were performed, revealing that FNC directly binds to Jagged1. This study provides valuable insights into the therapeutic potential of FNC in HCC treatment and elucidates its underlying mechanisms."

Journal • Hematological Malignancies • Hepatocellular Cancer • Human Immunodeficiency Virus • Infectious Disease • Liver Cancer • Lung Adenocarcinoma • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Solid Tumor • CDH1 • HEY1

A Clinical Study of the Interactions Between Azvudine Tablets (FNC) and Rilpivirine Tablets (RPV) (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Henan Genuine Biotech Co., Ltd.

New P1 trial

A Clinical Study of the Interactions Between Azvudine Tablets (FNC) and Aluvia (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Henan Genuine Biotech Co., Ltd.

New P1 trial

A Pharmacokinetics and Safety Study of Azvudine Tablets in Subjects With Mild-To-Moderate GFR Decline in Renal Insufficiency and in Healthy Subjects (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Henan Genuine Biotech Co., Ltd.

New P1 trial • Nephrology • Renal Disease

A Clinical Study of the Interactions Between Azvudine Tablets (FNC) and Rifampicin Capsules (RIF) (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Henan Genuine Biotech Co., Ltd.

New P1 trial

A Clinical Study of the Interactions Between Azvudine Tablets (FNC) and Itraconazole Capsules (ICZ) (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Henan Genuine Biotech Co., Ltd.

New P1 trial

A Clinical Study of the Interactions Between Azvudine Tablets (FNC) and Tenofovir Alafenol Fumarate Tablets (TAF) (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Henan Genuine Biotech Co., Ltd.

New P1 trial

[14C] Mass Balance Clinical Trial of Azvudine in Healthy Male Subjects (clinicaltrials.gov) - P1 | N=6 | Completed | Sponsor: Henan Genuine Biotech Co., Ltd.

New P1 trial