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

Hope on the horizon: Emerging therapies for hepatitis D. (PubMed, World J Hepatol) - "Pegylated interferon lambda acts on interferon-lambda (Type III) receptors predominantly expressed in hepatocytes. In 2023, bulevirtide was approved in the European Union and Russia for treating chronic hepatitis D. This drug works by binding to and inhibiting the sodium taurocholate co-transporting polypeptide receptor on liver cells, which is the primary entry point for the virus...Two more viral entry inhibitors are HH003 and tobevibart. Other agents include nucleic acid polymers (REP 2139-Mg), prenylation inhibitors (lonafarnib), and RNA interference-based therapies (elebsiran)...The efficacy and safety of these drugs will further be evaluated in ECLIPSE 1, 2, and 3 trials. With these new treatments on the horizon, the prospects for improved HDV patient outcomes are promising."

Journal • Review • Hepatitis B • Infectious Disease • Inflammation • IFNA1

Advances in treatment of hepatitis delta virus infection: Update on novel investigational drugs. (PubMed, World J Virol) - "Significant unmet medical needs remain in the treatment of HDV, and recent advances in drug development offer hope for meaningful advances in drug therapy which may improve virologic response rates and clinical outcomes. This review summarizes trial design and available efficacy data from key phase 2 and 3 trials for investigational therapies including entry inhibitors (bulevirtide), prenylation inhibitors (lonafarnib), novel IFNs (peginterferon lambda), RNA interference molecules (JNJ-3989, elebsiran), monoclonal antibodies (tobevibart), and nucleic acid polymers (REP2139), and addresses future directions in HDV pharmacotherapy."

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

Assessing the Efficacy of Small Molecule Drugs in Hutchinson-Gilford Progeria Syndrome: A Review of Clinical Trials. (PubMed, Rev Recent Clin Trials) - "Farnesyltransferase inhibitors (FTIs) have shown potential in mitigating disease phenotypes in preclinical models, with lonafarnib achieving FDA approval in 2020 as the first-and currently only-drug for progeria treatment. This review focuses on the clinical trial outcomes of small-molecule therapeutics for progeria, with particular emphasis on emerging small molecules from recent research. These novel compounds, with their unique mechanisms of action, hold promise not only for improving disease management but potentially offering a cure for this devastating condition."

Journal • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders • Myocardial Infarction • Rare Diseases • LMNA

Hepatitis D Virus Infection: Pathophysiology, Epidemiology and Treatment. Report From the Third Delta Cure Meeting 2024. (PubMed, Liver Int) - "The improved knowledge of the HDV life cycle has led to the development and approval of the first HDV-direct antiviral, Bulevirtide (BLV)...Despite recent advances in antiviral treatment, strategies to achieve HBsAg loss, which most closely resembles HDV cure, are not available and antiviral treatment for patients with advanced liver disease is limited. The third international Delta Cure meeting, held in Milan in October 2024, aimed to share the latest findings, and this review highlights key takeaways from the lectures and research on HDV."

Journal • Review • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Oncology • Solid Tumor • IFNA1 • KEAP1

Baricitinib and Lonafarnib Synergistically Target Progerin and Inflammation, Improving Lifespan and Health in Progeria Mice. (PubMed, Int J Mol Sci) - "Mechanistically, BAR decreased the SASP and inflammatory markers (e.g., IL-6 and PAI-1), complementing the progerin-targeting effects of FTI. This preclinical study demonstrates the synergistic potential of BAR + FTI therapy in addressing HGPS systemic and tissue-specific pathologies, offering a promising strategy for enhancing both lifespan and health."

Journal • Preclinical • Cataract • Fibrosis • Immunology • Inflammation • Ophthalmology • IL6

Fibronectin Extra Domain A Degradation as an Antifibrotic Approach in Lung Fibrosis (ATS 2025) - "FN-EDA half-life is ∼12 h and its turnover occurs in lysosomes. The farnesyl-transferase inhibitor lonafarnib increased lysosomal activity in primary human lung fibroblasts and reduced FN-EDA levels in vitro. Lonafarnib reversed the effects of TGFβ-induced FN-EDA up-regulation."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis • TGFB1

Clinical Trials for Hepatitis Delta Virus in the WHO African region: A neglected virus among neglected viruses. (PubMed, J Infect) - "HDV-focused CT are needed in the WHO African region, as the region with the highest disease burden, and unique genotypes (5-8); to evaluate efficacy of novel anti-HDV compounds and to ensure that new treatments can be distributed and deployed as they become available."

Journal • Review • Inflammation

EFFICACY AND SAFETY OF TREATMENTS FOR CHRONIC HEPATITIS D: A SYSTEMATIC REVIEW AND META-ANALYSIS OF 19 RANDOMIZED CONTROLLED TRIALS (DDW 2025) - "Objective: This meta-analysis evaluates the efficacy and safety of pharmacological treatments for chronic HDV, including Lamivudine, Peg-IFN, Ribavirin, IFN alfa-2a, Adefovir, Bulevirtide, Lonafarnib, TDF, and Entecavir... Bulevirtide with Peg-IFN is the most effective and safest treatment for chronic HDV, particularly in cirrhotic patients. TDF shows potential but requires further study in larger, long-term trials. Adverse effects from therapies like Peg-IFN and Lonafarnib emphasize the need for careful monitoring."

Retrospective data • Review • Anemia • Fatigue • Gastrointestinal Disorder • Hematological Disorders • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Liver Cirrhosis • Pain

Mesenchymal Stem Cell Therapy for Hutchinson-Gilford Progeria: Improvements in Arterial Stiffness and Bone Mineral Density in a Single Case. (PubMed, Children (Basel)) - "MSC therapy may offer short-term benefits in arterial stiffness, bone health and inflammation in HGPS without notable safety concerns. Further studies are warranted to validate these findings, explore earlier intervention, and determine long-term efficacy and optimal dosing strategies."

Journal • Atherosclerosis • Cardiovascular • CNS Disorders • Genetic Disorders • Inflammation • Musculoskeletal Diseases • Vascular Neurology • LMNA

Combining prelamin A accumulation and oxidative stress: A strategy to target glioblastoma. (PubMed, Eur J Cell Biol) - "By inhibiting the farnesyltransferase enzyme using SCH66336 (Lonafarnib), we promote the accumulation of lamin A precursor (prelamin A) in glioblastoma cells, thereby increasing their susceptibility to oxidative stress induced by Menadione administration, while sparing normal human astrocytes...These findings indicate that inhibiting prelamin A processing could be a potential strategy to reduce glioblastoma aggressiveness and enhance therapeutic outcomes, particularly for treatment-resistant glioblastoma stem cell populations. This approach shows potential for integrating prelamin A processing disruption as a complementary strategy in glioblastoma therapy."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Current and future therapeutic options for chronic hepatitis D virus infection. (PubMed, Front Cell Infect Microbiol) - "The old weapons are PegIFNα and recently PegIFN-lambda (PegIFNλ). PegIFNα, for which there are more data, appears to be an excellent combination regimen, if not contraindicated, both for Bulevirtide (BLV), data supported by important clinical trials and real-world studies, and probably for lonarfanib, although in the latter case the results are not yet definitive as the studies are fewer. However, data on long-term follow-up are needed."

Journal • Review • Hepatology • Infectious Disease • Inflammation • IFNA1

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=16 | Recruiting | Sponsor: PRG Science & Technology Co., Ltd.

New P2 trial

Longitudinal Changes in Myocardial Deformation in Hutchinson-Gilford Progeria Syndrome. (PubMed, Circ Cardiovasc Imaging) - No abstract available

Journal • Cardiovascular

Antiviral therapy for chronic hepatitis delta: new insights from clinical trials and real-life studies. (PubMed, Gut) - "In 2020, the European Medicines Agency approved bulevirtide (BLV) at 2 mg/day, an entry inhibitor of hepatitis B virus (HBV)/hepatitis delta virus (HDV), which proved to be safe and effective as a monotherapy for up to 144 weeks in clinical trials and real-life studies, including patients with cirrhosis...The PegIFN lambda study has been discontinued due to liver toxicity issues, while lonafarnib boosted with ritonavir showed limited off-therapy efficacy in a phase 3 study. Nucleic acid polymer-based therapy is promising but large studies are still lacking. New controlled trial data come from molecules, such as monoclonal antibodies and/or small interfering RNA, that target HBsAg or HBV RNAs, which demonstrated not only profound HDV suppression, but also HBsAg decline.While waiting for new compounds to be approved as monotherapy or in combination, BLV monotherapy 2 mg/day remains the only approved therapy for CHD, at least in the European Union region."

Journal • Review • Fibrosis • Hepatitis B • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • IFNA1

Lonafarnib Protects Against Muscle Atrophy Induced by Dexamethasone. (PubMed, J Cachexia Sarcopenia Muscle) - "Lonafarnib mitigates dexamethasone-induced muscle atrophy by enhancing mitochondrial function and activating anabolic pathways. These findings support further investigation of lonafarnib as a therapeutic agent for muscle atrophy in clinical settings."

Journal • Muscular Atrophy • ANGPTL4

Repurposing of lonafarnib as a treatment for SARS-CoV-2 infection. (PubMed, JCI Insight) - "LNF at clinically relevant dose suppressed viral titer in the respiratory tract and improved pulmonary pathology and clinical parameters. Our study demonstrated that LNF, an approved oral drug with excellent human safety data, is a promising antiviral against SARS-CoV-2 that warrants further clinical assessment for treatment of COVID-19 and potentially other viral infections."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Chronic Hepatitis D Virus Infection and Its Treatment: A Narrative Review. (PubMed, Microorganisms) - "These newer antiviral therapies include buleviritide (which blocks HDV entry), lonafarnib (which prevents HDV assembly), and REP-2139 (which prevents HDV export). In this manuscript, we discuss the characteristics of HDV infection and review the new antiviral therapies approved for treatment and those under investigation."

Journal • Review • Fibrosis • Hematological Disorders • Hepatitis B • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Neutropenia • Oncology • Psychiatry • Solid Tumor • Thrombocytopenia

Circular-RNA telomerase reverses endothelial senescence (AHA 2024) - "These hallmarks of aging are substantially reversed by treatment with telomerase (hTERT) linear RNA,with greater benefit in HGPS cells than the current therapy, lonafarnib... hTERT circRNA is more effective than hTERT linear RNA in rejuvenating senescent ECs, possibly because of its longer half-life. The novel hTERT circRNA is a promising therapy for HGPS and other disorders associated with accelerated vascular aging."

Circular RNA • Cardiovascular • CDKN1A • CXCL8 • IL1B • IL6

Lonafarnib and Temozolomide in Treating Patients with Glioblastoma Multiforme That is Recurrent or Did Not Respond to Previous Treatment with Temozolomide (clinicaltrials.gov) - P1 | N=34 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial primary completion date: Dec 2025 ➔ Mar 2025

Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor

CHARACTERIZATION OF HDV RNA AND HBSAG DURING PEGYLATED INTERFERON-ALPHA AND RITONAVIR-BOOSTED LONAFARNIB COMBINATION THERAPY: THE D-LIVR STUDY (AASLD 2024) - P3 | "The MP, BP, and TP kinetic profiles were associated with reaching on treatment HDV TND. Not reaching HDV TND at EOT had a 97% NPV for sustained HDV TND. Lastly, a >1.5 log decline in HBsAg was associated with sustained HDV TND."

Combination therapy • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Lonafarnib and Temozolomide in Treating Patients With Glioblastoma Multiforme That Is Recurrent or Did Not Respond to Previous Treatment With Temozolomide (clinicaltrials.gov) - P1 | N=35 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Dec 2022 ➔ Dec 2025 | Trial primary completion date: Dec 2022 ➔ Dec 2025

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor

EXPLORING BLOOD-BRAIN BARRIER-PENETRATING DRUGS FOR THE IDENTIFICATION OF NOVEL THERAPIES IN GLIOBLASTOMA (SIOP 2024) - " Seven drugs: Obatoclax (Mesylate), COG1410, Fingolimod, Ozanimod, Lonafarnib, BMS-202 and Bazedoxifene (acetate) were screened out as potential candidates, with consistent efficacy against glioblastoma cells, providing promising avenues for standalone therapies in GBM or as enhancers of existing conventional chemotherapy regimens. This multi-faceted approach aims to develop personalized and effective treatment strategies for the challenging landscape of glioblastoma tumors. This work was supported by FAPESP grant numbers 2022/09037-3, National Council for Scientific and Technological Development (CNPq, MCTI, Brazil) grant number 406484/2022-8 (INCT BioOncoPed)"

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Farnesyltransferase inhibitor Lonafarnib regulates cytokine production in influenza A virus infected human alveolar epithelial cells and macrophages (ISIRV-OPTIONS XII 2024) - No abstract available

Infectious Disease • Influenza • Respiratory Diseases

The NLRP3 inhibitor Dapansutrile improves the therapeutic action of lonafarnib on progeroid mice. (PubMed, Aging Cell) - "The combination of both drugs reduced the inflammation and senescence, extended survival and ameliorated various progeroid defects both in vitro and in vivo, compared with treatment using lonafarnib alone. These findings and the safety of dapansutrile demonstrated in several clinical trials proposes it as a possible co-adjuvant treatment with lonafarnid in HGPS."

Journal • Preclinical • Hepatology • Inflammation • NLRP3

Anesthetic Management of Cardiopulmonary Bypass in Hutchinson-Gilford Progeria Syndrome: A Case Report. (PubMed, A A Pract) - "Treatment with lonafarnib has improved survival in patients with HGPS; however, in extended longitudinal follow-up, there has been an increase in the prevalence of rapidly progressive calcific aortic stenosis. The evolving course of HGPS has prompted reconsideration of conservative management and led to the development of strategies for anatomic treatment. In this case report, we describe the anesthetic management of patients with HGPS undergoing surgical management of aortic stenosis with cardiopulmonary bypass."

Journal • Anesthesia • Atherosclerosis • Cardiovascular • CNS Disorders • Dyslipidemia • Vascular Neurology