vonafexor (EYP001) / Poxel SA, ENYO - LARVOL DELTA

Pharmacokinetic Comparison of Vonafexor Acid and Its Lysine Salt and Evaluation of Potential Drug-Drug Interactions (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Enyo Pharma

New P1 trial • CYP2C9

From RAAS blockade to regenerative medicine: evolving treatment strategies in Alport syndrome. (PubMed, Pediatr Nephrol) - "Adjunctive commercially available metabolic modulators, including SGLT2i, mineralocorticoid receptor antagonists, ezetimibe and GLP-1 receptor agonists, may offer additional kidney protection. Ameliorating therapies being tested in Phase II trials include endothelin receptor antagonists (e.g., atrasentan), dual endothelin receptor antagonist and angiotensin II receptor inhibition (e.g., sparsentan) FXR agonists (e.g., vonafexor), inducers of cholesterol efflux (e.g., VAR200 and R3R01), and NOX1/4 inhibitors (e.g., setanaxib), several of which are currently being evaluated in clinical trials. Novel strategies such as exon skipping, gene editing, and nonsense mutation readthrough (e.g., ELX-02) are advancing toward precision medicine approaches as disease modifying agents targeting the genetic cause of AS...This review summarizes the current landscape of AS classification and treatment, highlighting both standard interventions and experimental therapies. Emphasis is placed..."

Journal • Review • Fibrosis • Gene Therapies • Genetic Disorders • Glomerulonephritis • Immunology • Renal Disease • COL4A5

Vonafexor in Progressive Alport Syndrome: Early Evidence of Kidney Function Benefit from the ALPESTRIA-1 Trial (KIDNEY WEEK 2025) - "The dissociation of eGFR recovery from proteinuria argues against a purely hemodynamic effect and supports a potential disease-modifying effect. A phase 3 trial is in preparation."

Late-breaking abstract • Chronic Kidney Disease • Dermatology • Genetic Disorders • Hepatology • Inflammation • Metabolic Disorders • Nephrology • Pruritus • Renal Disease

Vonafexor, a Selective FXR Agonist, as a Novel Therapeutic Strategy in CKD (KIDNEY WEEK 2025) - "Comparisons were made with Losartan and other FXR agonists. Conclusion Together, our results demonstrate that Vonafexor significantly attenuates CKD progression in experimental models by modulating the Wnt–β-catenin signaling pathway, surpassing the efficacy of current treatments. These preclinical findings, combined with clinical data from the LIVIFY phase 2 trial showing improved eGFR in NASH patients with CKD, underscore the therapeutic potential of Vonafexor as a novel therapeutic strategy for CKD."

Chronic Kidney Disease • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Renal Disease

NEW SUBMISSIONA LONG-ACTING AQUEOUS NANOSUSPENSION OF VONAFEXOR PRODRUG ATTENUATES LIVER FIBROSIS DEVELOPMENT IN CCL4 MOUSE FIBROSIS MODEL (AASLD 2025) - "Administered monthly, NM2Von reduced liver fibrosis development, presumably due to decreased activation of HSC. This indicates its potential efficacy in preventing/attenuating liver fibrosis, a frequent outcome of HBV infection. These promising preclinical data support the potential clinical translation of this novel long-acting NM2Von formulation."

Preclinical • Fibrosis • Hepatitis B • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • TGFB1

Obeticholic Acid and Other Farnesoid-X-Receptor (FXR) Agonists in the Treatment of Liver Disorders. (PubMed, Pharmaceuticals (Basel)) - "Obeticholic acid (OCA), a semisynthetic derivative of chenodeoxycholic acid (CDCA), initially named 6-ethyl-CDCA or INT-747, is the first in a class of FXR ligands that have been approved for clinical use for the treatment of patients with primary biliary cholangitis (PBC) who are unresponsive or intolerant to ursodeoxycholic acid...Here, we review potential applications of OCA in PBC patients in the context of a highly competitive therapeutic landscape, generated by the approval for clinical use of safer and effective second-line therapies, including PPARs agonists such as elafibranor and seladelapar and increased off-label use of fibrates. The current status of development of second-generation FXR agonists such as cilofexor, tropifexor, and vonafexor and their potential in the treatment of liver fibrosis in MASH will be discussed and compared to recently approved therapies, resmetirom, and semaglutide, a GLP-1 agonist. Finally, since some of the novel candidates for..."

Journal • Review • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Primary Biliary Cholangitis

Vonafexor in Patients With Impaired Renal Function and Suspected MASH (Metabolic Dysfunction-associated Steatohepatitis) (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Enyo Pharma | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Kidney Disease • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Renal Disease

New mechanistic understanding of FXR agonist Vonafexor: inducing sublethal damage of HBV-positive liver cancer cells via promoting anti-tumor immunity. (PubMed, Br J Cancer) - "Our study indicated that Vonafexor showed potential as an immunotherapy for HBV-positive HCC."

IO biomarker • Journal • Hepatitis B • Hepatocellular Cancer • Infectious Disease • Liver Cancer • Oncology • Solid Tumor • Transplantation • CD36 • GZMB • SCARB1 • STING

Vonafexor in Patients With Impaired Renal Function and Suspected MASH (Metabolic Dysfunction-associated Steatohepatitis) (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Enyo Pharma

New P2 trial • Chronic Kidney Disease • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Renal Disease

Change in cT1 following interventions in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis (EASL 2025) - "By treatment type, fibroblast growth factor (FGF) analogues (aldafermin; pegozafermin), glucagon-like peptide (GLP)-1 receptor agonists (pemvidutide; tirzepatide) and farnesoid X receptor (FXR) agonists (vonafexor; ocaliva; TERN-101), cT1 had a mean change of -79ms [95% CI: -90, - 68], -68ms [95% CI: -77, -58] and -62ms [95% CI: -74, -49], respectively... Evidence to-date supports a significant treatment-induced reduction in cT1 as compared to minimal changes in the placebo group. Our findings could inform current and future study designs for investigational therapies for liver disease and support monitoring of treatment response in individuals with MASLD in clinical trials and clinical practice."

Retrospective data • Review • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF

A novel in vitro system for simultaneous infections with hepatitis B, C, D and E viruses. (PubMed, JHEP Rep) - "We recapitulated the known antiviral effect of sofosbuvir on HCV and HEV (>90% reduction in the levels of intracellular viral RNAs, p <0.0005) and of IFN-α on HCV, HEV and HDV (80% reduction in the levels of intracellular viral RNAs, p <0.0005)...Using HEV-infected HuHep mice, we confirmed the antiviral effect of vonafexor, an FXR agonist, that is currently being tested clinically against HBV/HDV...Moreover, the interplay between these four viruses in the context of co-infections remains unknown. In this study, we report the first in vitro system that allows for mono and multi-infections with these four viruses and characterize the broad antiviral activity of farnesoid X receptor agonists, paving the way for the development of new strategies for viral cure."

Journal • Preclinical • Hepatitis B • Hepatology • Infectious Disease • Inflammation • APOB • IFNA1

Change in cT1 following interventions in MASLD: A systematic review and meta-analysis (APASL 2025) - "By treatment type, fibroblast growth factor (FGF) analogues (aldafermin; pegozafermin), glucagon-like peptide (GLP)-1 receptor agonists (pemvidutide; tirzepatide) and farnesoid X receptor (FXR) agonists (vonafexor; ocaliva; TERN-101), cT1 had a mean change of -79ms [95% CI: -90, -68], -68ms [95% CI: -77, -58] and -62ms [95% CI: -74, -49], respectively... Evidence to-date supports a significant treatment-induced reduction in cT1 as compared to minimal changes in the placebo group. Our findings could inform current and future study designs for investigational therapies for liver disease and support monitoring of treatment response in individuals with MASLD in clinical trials and clinical practice. Table and Figure:Figure 1.Figure."

Retrospective data • Review • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF

Vonafexor ALPort Syndrome Efficacy & Safety TRIAl-1 (ALPESTRIA-1) (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: Enyo Pharma | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • LCN2

Vonafexor ALPort Syndrome Efficacy & Safety TRIAl-1 (ALPESTRIA-1) (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Enyo Pharma | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • LCN2

Vonafexor ALPort Syndrome Efficacy & Safety TRIAl-1 (ALPESTRIA-1) (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Enyo Pharma

New P2 trial • Genetic Disorders • LCN2

VONAFEXOR AS A NOVEL THERAPY FOR CHRONIC KIDNEY DISEASE (ERA-EDTA 2023) - "The possible beneficial effect was compared to that of Losartan and other NR1H4 agonists. Altogether our results identified in Vonafexor a novel key drug to control CKD. This is consistent with recent results obtained in LIVIFY phase 2 clinical trial in which Vonafexor has already demonstrated beneficial effects on eGFR in NASH patients with mild to moderate CKD."

Chronic Kidney Disease • Fibrosis • Glomerulonephritis • Hepatology • Immunology • Inflammation • Nephrology • Non-alcoholic Steatohepatitis • Renal Disease • Collagen Type IV

[VIRTUAL] A phase 2 study testing FXR agonist Vonafexor in treatment naive patients with chronic hepatitis B (CHB): preliminary week 16 results (EASL-ILC 2021) - P2a | " In this ongoingmulti-center, randomized, open-label Phase 2 trial (NCT04365933) treatment naive CHB patients with HBsAg ≥300 IU/ml and HBV DNA ≥20’000 IU/ml for HBeAg+ and ≥2’000 for HBeAg- were randomized to a combination of oral V 200 mg QDwith sc pegylated interferon alpha2a (peg-IFN 180 mcg QW) to which entecavir (0.5 mg QD, ETV) was added (arm 1) or not (arm 2). Vonafexor combined with peg-IFN induces a marked HBsAg decline in HBeAg- treatment naive CHB patients. No relationship between transaminase flares and viral response was found. Additional data is being collected during the ongoing follow- up period."

Clinical • P2 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Pharmacological characterization of second generation FXR agonists as effective EphA2 antagonists: a successful application of target hopping approach. (PubMed, Biochem Pharmacol) - "Herein we characterize new commercially available FXR (Farnesoid X Receptor) agonists as potential Eph ligands including Cilofexor, Nidufexor, Tropifexor, Turofexorate isopropyl and Vonafexor. Furthermore, Cilofexor interferes with the phosphorylation of EphA2 and the cell retraction and rounding in PC3 prostate cancer cells, both events depending on EphA2 activation. In conclusion, we can confirm that target hopping can be a successful approach to discover new moiety of protein-protein inhibitors."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH. (PubMed, J Hepatol) - P2a | "In patients with suspected fibrotic NASH, Vonafexor was safe and induced potent liver fat reduction, improvement in liver enzymes, weight loss, and a possible renal benefit."

Journal • Chronic Kidney Disease • Dermatology • Fibrosis • Hepatitis C • Hepatology • Immunology • Liver Cirrhosis • Nephrology • Non-alcoholic Steatohepatitis • Pruritus • Renal Disease

Study of EYP001a to Assess Its Safety and Anti-viral Effect in CHB Patients in Combination With NA (ETV or TD) (clinicaltrials.gov) - P2a | N=26 | Terminated | Sponsor: Enyo Pharma | New randomizations were stopped. Already randomized subjects were followed up to W40.

Combination therapy • Enrollment change • Trial termination • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Solid Tumor

A Study of the Oral Farnesoid X Receptor Modulator EYP001a to Assess Its Safety and Anti-viral Effect in Chronic Hepatitis B Patients in Combination With Pegylated Interferon alpha2a Alone and With Entecavir (clinicaltrials.gov) - P2a | N=20 | Completed | Sponsor: Enyo Pharma | Active, not recruiting ➔ Completed | N=30 ➔ 20

Combination therapy • Enrollment change • Trial completion • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Solid Tumor • FGF19

Combined effect of Vonafexor and Interferon-alpha on HBV replication in primary human hepatocytes (EASL-ILC 2022) - P2a | "We were able to recapitulate, in cell culture models, the improved anti-HBV effect of combining Vonafexor and peg-IFNα. We also observed that the effect is achieved without inducing toxicity. This study provides support for the existence of a mechanism of action underlying the antiviral activity in combining Vonafexor and peg-IFNα, details of which should be explored further to eventually assist in identifying efficacy predictive factors in clinical trials."

Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNA1

Potential for FDA approval nears for emerging NASH therapies (Healio) - "'We [have] a huge armamentarium of drugs in development,' Manal F. Abdelmalek, MD...'In my opinion, the future of NASH is going to be binding combination therapies, for which we have a foundation of anti-metabolic therapy, coupled with anti-inflammatory or anti-fibrotic therapy, depending on where patients are in the disease spectrum.'"

Media quote

[VIRTUAL] VONAFEXOR, A FXR AGONIST, INDUCED HEPATIC AND RENAL IMPROVEMENT IN THE RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED LIVIFY NASH TRIAL (AASLD 2021) - "VONA induced a strong, consistent LFC reduction, and improvement in biochemical and imaging markers of liver inflammation with an added benefit on eGFR. VONA was safe and well tolerated, with the 100 mg dose showing a more favorable tolerability-efficacy profile. Larger trials are warranted to confirm the hepatic and renal benefits."

Clinical • Late-breaking abstract • Chronic Kidney Disease • Dermatology • Diabetic Nephropathy • Dyslipidemia • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Nephrology • Non-alcoholic Steatohepatitis • Pruritus • Renal Disease • MRI

ENYO Pharma Announces Two Vonafexor Data Presentations at AASLD The Liver Meeting (Businesswire) - "A poster on modelling efforts to optimize the study design of a combination of Vonafexor and Peg-IFN in chronic HBV patients...The second abstract refers to a poster presentation on modelling efforts by our collaborators from Novadiscovery to optimize the combination of Vonafexor and Peg-IFN in HBV patients."

Clinical protocol • Hepatitis B • Infectious Disease