Zokinvy (lonafarnib) / Eiger, AnGes MG - LARVOL DELTA

Lonafarnib as finite treatment for chronic hepatitis D: Long-term follow-up data (APASL 2026) - No abstract available

Hepatology • Inflammation

Lonafarnib/ritonavir and peg-Interferon alfa drive histological improvement and inflammation resolution in chronic hepatitis D: results of the multicenter phase 3 D-LIVR study (EASL 2026) - No abstract available

Clinical • P3 data • Hepatology • Inflammation

Lonafarnib as finite treatment for chronic hepatitis D: Long-term effect on hard endpoints (EASL 2026) - No abstract available

Hepatology • Inflammation

Lonafarnib/ritonavir with or without peginterferon achieves rapid, durable responses in a chronic hepatitis D: extended analyses from the phase 3 D-LIVR trial (EASL 2026) - No abstract available

P3 data • Hepatology • Inflammation

Heat stroke-induced structural and functional impairments of cognition-relevant brain areas in mice is associated with alpha-7 nicotinic acetylcholine receptors downregulation. (PubMed, Eur J Pharmacol) - "CHS is associated with structural and functional impairments in cognition-relevant brain regions, accompanied by reduced α7nAChR expression. Lonafarnib mitigated CHS-related neurobehavioral abnormalities in parallel with restoration of α7nAChR expression in mice."

Journal • Preclinical • Behavior Disorders • Cardiovascular • Cognitive Disorders • Mental Retardation • Psychiatry

Utilizing bulk and single-cell RNA sequencing to identify potential biomarkers linked to angiogenesis and integrated stress response in chondrosarcoma. (PubMed, Sci Rep) - "Moreover, 9 transcription factors (TFs) (like STAT1), 69 key microRNAs (miRNAs) (like hsa-miR-361-3p), and 78 long non-coding RNAs (lncRNAs) (like NEAT1) were found to have relationships with potential biomarkers, and potential biomarkers had stable binding affinity with adenosine diphosphate (ADP) and lonafarnib...Importantly, RT-qPCR confirmed higher expression of HSPA8, LMNA and SERPINH1 in CS patients. The findings suggested that HSPA8, LMNA and SERPINH1 might offer novel insights for the development of targeted therapies for CS associated with angiogenesis and ISR."

Biomarker • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • Targeted Protein Degradation • HSPA8 • LMNA • MIR361 • NEAT1 • SERPINH1 • STAT1

Targeted Sensitization of Leukemic T-cells to Anticancer Drugs by SIRT1 Agonist SRT-1720. (PubMed, Anticancer Res) - "SRT-1720 induces oxidative stress and apoptosis in leukemic lymphocytes through SIRT1-independent pathway(s). In contrast, it enhances antioxidant defense in normal lymphocytes through a SIRT1-dependent pathway. These findings highlight the potential of SRT-1720 as an adjuvant to chemotherapy in T-ALL, particularly in drug combinations demonstrating strong synergism, which may allow dose reduction and decreased toxicity."

Journal • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • SIRT1

PRG-PRO-005: Study to Determine Optimal Dose and Evaluate Safety, Tolerability, and Pharmacokinetics of Progerinin in Patients With Hutchinson-Gilford Progeria Syndrome (HGPS) (clinicaltrials.gov) - P2 | N=10 | Active, not recruiting | Sponsor: PRG Science & Technology Co., Ltd. | Recruiting ➔ Active, not recruiting | N=16 ➔ 10 | Trial completion date: Dec 2025 ➔ Mar 2026 | Trial primary completion date: Dec 2025 ➔ Mar 2026

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • LMNA

Dapansutrile in multidisciplinary therapeutic applications: mechanisms and clinical perspectives. (PubMed, Front Pharmacol) - "Furthermore, dapansutrile exhibits synergistic effects when combined with agents such as lonafarnib or immune checkpoint inhibitors, enhancing anti-inflammatory and anti-tumor responses. This review consolidates evidence on dapansutrile's molecular mechanisms, therapeutic applications, and biosafety, highlighting its potential as a novel, well-tolerated, and versatile anti-inflammatory agent. Future research should focus on optimizing its delivery, particularly to the central nervous system, and leveraging artificial intelligence to predict effective drug combinations."

Journal • Review • Cardiovascular • CNS Disorders • Dental Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Arthritis • Inflammatory Bowel Disease • Oncology • Periodontitis • Rheumatology • IL18 • IL1B • NLRP3

Molecular mechanism of resistance to lonafarnib conferred by mutations in the cysteine-rich region of respiratory syncytial virus fusion glycoprotein and discovery of a lonafarnib-derived antiviral PROTAC. (PubMed, J Virol) - "This novel antiviral agent effectively inhibits RSV infection by inducing degradation of the F protein. This work elucidates the molecular basis of RSV resistance to lonafarnib and establishes a strategy for developing next-generation antivirals aimed at preempting resistance."

Journal • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • Targeted Protein Degradation • CRBN

Lonafarnib Clinical Trials Demonstrate Uncoupling of the Muscle-Bone Unit in Hutchinson-Gilford Progeria Syndrome. (PubMed, J Bone Miner Res) - "Normal muscle mass for body size at younger ages implies that there is an opportunity for early treatment to avoid impending pathology. New strategies are needed to ameliorate this phenotype in HGPS, and this study provides a benchmark for gauging future therapies."

Journal • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Heart Failure • Orthopedics • Pediatrics

Inhibition of farnesyltransferase activity diminishes hematopoietic stem cell ex vivo expansion ability. (PubMed, bioRxiv) - "The rationale underlying this work is that elucidating the contribution of farnesyltransferase activity to hematopoietic stem cell expansion ex vivo will provide knowledge needed to better support hematopoietic stem cell expansion techniques for clinical applications that rely on this approach, like hematopoietic cell transplants and gene therapy. We discovered that pharmacological inhibition of farnesyltransferase activity with lonafarnib substantially diminished the ex vivo expansion potential of human and mouse hematopoietic stem cells, highlighting that hematopoietic stem cells rely on isoprenoids for their ex vivo maintenance."

Journal • Preclinical • Gene Therapies • Transplantation

Farnesyltransferase inhibitors decrease matrix-vesicle-mediated mineralization in SaOS-2 cells. (PubMed, Mol Biol Rep) - "Our findings demonstrate that FTIs Lonafarnib and Tipifarnib impair MVM, highlighting the essential role of farnesylation in biomineralization."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • COL1A1 • RUNX2

Baricitinib Augments Lonafarnib Therapy to Preserve Colonic Homeostasis and Microbial Balance in a Mouse Model of Progeria. (PubMed, Aging Cell) - "While both monotherapies induced distinct shifts in gut microbiota, combination therapy preserved a profile more closely resembling healthy controls. These findings expand the current understanding of GI involvement in HGPS and identify the colon as a site where JAK-STAT inhibition enhances the therapeutic profile of FTI."

Journal • Preclinical • Fibrosis • Gastrointestinal Disorder • Genetic Disorders • Inflammation • STAT1

Selection of specific and efficient siRNAs in new cellular model for Hutchinson-Gilford progeria syndrome therapy. (PubMed, Mol Ther Nucleic Acids) - "Additionally, we observed an additive effect of the combination of our siRNAs with lonafarnib-the sole drug approved by the Food and Drug Administration for progeria syndrome therapy. The selected siRNAs also worked efficiently in all three tested patient fibroblast lines, even after extended post-transfection incubation with low siRNA doses. Therefore, we believe that the development of genetic drugs may be a promising therapeutic tool for Hutchinson-Gilford progeria syndrome."

Journal • Gene Therapies • Genetic Disorders • LMNA

LONAFARNIB AS FINITE TREATMENT FOR CHRONIC HEPATITIS D: LONG-TERM FOLLOW-UP DATA (AASLD 2025) - "Patients achieving a 2 log drop in HDV RNA from baseline and normal ALT at 6 months after stopping any finite lonafarnib-based treatment regimen have no major clinical events (liver decompensation, liver cancer, or death) in up to 10 years of follow-up."

Hepatology • Infectious Disease • Inflammation • Liver Cancer • Liver Failure • Solid Tumor

LONAFARNIB AS FINITE TREATMENT FOR CHRONIC HEPATITIS D: LONG-TERM FOLLOW-UP DATA (AASLD 2025) - "Patients achieving a 2 log drop in HDV RNA from baseline and normal ALT at 6 months after stopping any finite lonafarnib-based treatment regimen have no major clinical events (liver decompensation, liver cancer, or death) in up to 10 years of follow up."

Hepatology • Infectious Disease • Inflammation • Liver Cancer • Liver Failure • Solid Tumor

COMPARING THE EFFICACY OF BULEVERTIDE, INTERFERONS, AND NUCLEOSIDE ANALOGS IN THE MANAGEMENT OF CHRONIC HEPATITIS DELTA: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS (AASLD 2025) - "Several therapies such as Lamivudine, Tenofovir, Interferons, and newer drugs like Lonafarnib, Bulevirtide have been tried with variable success. Bulevirtide in combination with Pegylated interferon alpha may be the most promising therapy for chronic Hepatitis D, while monotherapy with HBV-directed NAs are not as effective. The side effects of interferon therapy also cannot be overstated. Larger RCTs with Bulevirtide + Peginterferon alpha should be conducted."

Retrospective data • Review • Fibrosis • Hepatology • Immunology • Inflammation

The Fall of the Armor: Lamin Dysregulation and a Wide Network of Laminopathies. (PubMed, Subcell Biochem) - "Lamins have also been shown to be dysregulated in a multitude of cancers, and research has uncovered a diabolical role of lamins in oncogenesis. The understanding of laminopathies and dysregulation of lamins resulting in disorders is critical in developing novel therapeutic strategies through drug repurposing and epigenetic modulation to curb the burden of the diseases."

Journal • Review • Cardiomyopathy • Cardiovascular • Genetic Disorders • Lipodystrophy • Metabolic Disorders • Muscular Dystrophy • Oncology • LMNA • LMNB1 • LMNB2

Hepatitis Delta Virus Infection: An Overview. (PubMed, Pathogens) - "Bulevirtide is the recently available treatment against hepatitis delta. The results of efficacy studies and new drugs (lonafarnib) are under discussion. New therapeutic strategies are in development, revealing a critical need for valid next-generation treatments to cure HDV."

Journal • Review • Fibrosis • Hepatitis B • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Liver Failure • Oncology • Solid Tumor

In Vitro synergy of Farnesyltransferase inhibitors in combination with colistin against ESKAPE bacteria. (PubMed, PLoS One) - "Tipifarnib exhibited more potent antimicrobial activity against gram-negative strains than lonafarnib...In contrast, alpha-hydroxy farnesyl phosphonic acid, an FPP analog, and bempedoic acid, targeting the mevalonate pathway, showed no antibacterial activity...This might be due to a mechanism distinct from their eukaryotic targets, potentially involving the disruption of multiple biosynthetic pathways. Future studies will focus on elucidating these mechanisms of FTIs and exploring the therapeutic potential of FTI/colistin combinations against ESKAPE and other multidrug-resistant pathogens."

Journal • Preclinical • Infectious Disease • Oncology • Pneumonia

Discovery of Tricyclic Derivative as Novel and Potent Respiratory Syncytial Virus Fusion Glycoprotein Inhibitor with an Improved Pharmacokinetic Profile. (PubMed, J Med Chem) - "Additionally, CGR-51 exhibits an improved pharmacokinetic profile and effectively suppresses RSV replication in a BALB/c mouse model of RSV infection, while showing lower toxicity compared to lonafarnib. Collectively, CGR-51 represents a promising RSV F protein inhibitor candidate for the treatment of RSV infection."

Journal • PK/PD data • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Surgical Aortic Valve Replacement Combined With Coronary Artery Bypass Grafting in a Patient With Progeria. (PubMed, JACC Case Rep) - "Surgical aortic valve replacement may be considered among the potential treatment options for selected patients with HGPS."

Journal • Cardiovascular • Coronary Artery Disease

Updates on Recent Advancements in Hepatitis D Virus Treatment. (PubMed, Viruses) - "Meanwhile, bulevirtide, an entry inhibitor, became the first agent to be approved for use in chronic HDV infections by the European Medicines Agency (EMA), and several other therapies are currently being investigated as well. In this review, we provide updates on recent advancements in HDV treatment and novel therapies."

Journal • Review • Fibrosis • Hepatitis B • Hepatitis C • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Oncology • Solid Tumor

The Hypomethylating Agent 5-Azacitidine Potentiates the Effect of RAS and Sp1 Inhibitors in Neuroblastoma Cells. (PubMed, Acta Naturae) - "Mithramycin A and lonafarnib were the two drugs that, in combination with 5-azacitidine, appeared to exert a synergistic effect on SH-SY5Y cell death. An analysis of the signaling pathways also revealed an activation of the signaling pathways associated with neuroblastoma cell differentiation, as well as apoptosis induction, as confirmed by multiplex and confocal microscopy. Hence, by analyzing the changes in the signaling pathways, the mechanisms of cell death and cell adaptation to hypomethylating agents can be understood, and this can be further used to develop novel therapeutic approaches to neuroblastoma therapy."

Journal • Gene Therapies • Neuroblastoma • Oncology • Pediatrics • Solid Tumor