efruxifermin (AKR-001) / Amgen, Novo Nordisk - LARVOL DELTA

Efruxifermin: “Statistically Significant Reduction in LSM with Efruxifermin at Week 96”; Metabolic dysfunction-associated steatohepatitis (Akero) - AASLD 2025

P2b data • Metabolic Dysfunction-Associated Steatohepatitis

Untapped potential of efruxifermin in lean MASH. (PubMed, Hepatol Int) - No abstract available

Journal • Metabolic Dysfunction-Associated Steatohepatitis

Efruxifermin: “In the SYMMETRY trial that enrolled participants with MASH and compensated cirrhosis (F4c), efruxifermin improved fibrosis by histology at Week 96”; Metabolic dysfunction-associated steatohepatitis (Akero) - AASLD 2025

P2b data • Metabolic Dysfunction-Associated Steatohepatitis

Novo Nordisk has completed its acquisition of Akero Therapeutics (GlobeNewswire) - "With the completion of the transaction, Novo Nordisk has acquired all outstanding shares of common stock and common stock equivalents of Akero for 54 USD per share in cash (or aggregated value of 4.7 billion USD) and a non-transferable Contingent Value Right ('CVR'). Each CVR entitles its holder to an additional payment of 6 USD per share in cash (or aggregated value of 0.5 billion USD) upon US regulatory approval of Akero’s lead candidate EFX for the treatment of compensated cirrhosis due to MASH."

M&A • Metabolic Dysfunction-Associated Steatohepatitis

Akero Therapeutics Presents New Analyses from Phase 2b SYMMETRY and HARMONY Trials of Efruxifermin at 76th Annual AASLD The Liver Meeting 2025 (GlobeNewswire) - "New post-hoc analyses of 96-week data from the SYMMETRY trial reinforce the antifibrotic activity of efruxifermin in F4c MASH: Efruxifermin was associated with statistically significant improvements in clinically significant portal hypertension (CSPH) risk, as assessed by Baveno criteria. CSPH, a serious complication of cirrhosis, increases risk of hepatic complications; Significantly more participants treated with efruxifermin vs. placebo met thresholds for clinically meaningful improvements in noninvasive measures of fibrosis that predict reduced risk of liver-related events....Additionally, an AI-powered digital pathology analysis (PathAI) of liver biopsies from the 96-week HARMONY trial in participants with F2/F3 MASH corroborated the previously reported fibrosis improvements shown by conventional pathology, providing further support for the improvements in fibrosis and MASH observed with efruxifermin."

P2b data • Metabolic Dysfunction-Associated Steatohepatitis

Role of FGF21 in Heart Failure: Molecular Insights and Therapeutic Implications. (PubMed, Cardiol Rev) - "Experimental models show that FGF21 protects against pressure overload, ischemia-reperfusion injury, doxorubicin cardiotoxicity, and diabetic cardiomyopathy by enhancing oxidative metabolism and autophagy, suppressing inflammation, boosting antioxidant defenses, and reducing fibrosis. In humans, circulating FGF21 levels are elevated across HF phenotypes and correlate with N-terminal pro-B-type natriuretic peptide, inflammatory cytokines, adverse remodeling, and poor prognosis, suggesting compensatory upregulation in the context of "FGF21 resistance." Long-acting FGF21 analogs developed for metabolic diseases, such as pegozafermin and efruxifermin, improve triglycerides, insulin sensitivity, and ectopic fat, highlighting potential cardiovascular benefit...This review integrates molecular, preclinical, and clinical evidence to position FGF21 as both a marker and a therapeutic target in HF. It aims to focus on mechanisms of action, evaluate its prognostic value,..."

Journal • Cachexia • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Inflammation • Metabolic Disorders • Osteoporosis • Reperfusion Injury • FGF21 • FGFR1 • FGFR4

Safety and Efficacy of Efruxifermin in Patients With Non-Alcoholic Steatohepatitis: A Meta-Analysis of Randomized Controlled Trials (ACG 2025) - "Three randomized controlled trials (RCTs) were included. Efruxifermin compared to placebo showed a significant improvement in liver fibrosis (≥1 stages) and no worsening of NASH at doses of 28 mg (RR = 22.5; 95% CI: 3.19, 158.72) and 50 mg (RR = 18.22; 95% CI: 3.44, 96.56). Improvement in liver fibrosis (≥1 stage) and resolution of NASH were observed at 28 mg (RR = 6.39; 95% CI: 1.78, 23.01) and 50 mg (RR = 7.49; 95% CI: 2.29, 24.57)."

Retrospective data • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Efficacy and Safety of Efruxifermin in Patients With MASH: A Meta-Analysis of Randomized Controlled Trials (ACG 2025) - "Four randomized controlled trials comprising 419 patients were included, with 284 patients receiving efruxifermin and 135 receiving placebo. Efruxifermin significantly increased the likelihood of MASH resolution without worsening (RR = 2.42; 95% CI: 1.48–3.94; p < 0.001), ≥1-stage fibrosis improvement without MASH worsening (RR = 1.83; 95% CI: 1.17–2.84; p = 0.01). It also led to significant improvements in MASH resolution and improvement (RR = 3.77; 95% CI: 1.10–12.87; p = 0.03)."

Retrospective data • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

Harnessing FGF21: A Meta-Analytic Evaluation of Efruxifermin's Efficacy and Safety in Non-Alcoholic Steatohepatitis (ACG 2025) - "Five RCTs encompassing various stages of NASH (F1–F4 fibrosis) were analyzed. The pooled analysis demonstrated that EFX significantly improved liver histology and metabolic parameters compared to placebo. Specifically, the relative risk (RR) for achieving ≥1-stage fibrosis improvement without NASH worsening was 1.87 (95% CI: 1.15 to 2.92; I² = 45%), indicating a substantial benefit of EFX over placebo."

Clinical • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

FGF19/FGF21 Analogues in NASH: Systematic Review (ACG 2025) - "We found eight trials of FGF21 analogues (Efruxifermin, Pegozafermin and Pegbelfermin) and two of the FGF19 analogue Aldafermin. Efruxifermin produced significant benefits: in the 24-week HARMONY trial (n=128, F2–F3 fibrosis), 39% of efruxifermin treated patients had ≥1 stage fibrosis improvement (no NASH worsening) vs 20% on placebo. In the 16-week BALANCED trial (F1–F3), efruxifermin decreased hepatic fat fraction on average by 13.26% vs 0.3% with placebo."

Review • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • FGF19 • FGF21

Safety and efficacy of 24 weeks of pemvidutide in metabolic dysfunction-associated steatotic liver disease: A randomized, controlled clinical trial. (PubMed, JHEP Rep) - P1 | "The current trial demonstrates that continued treatment with pemvidutide further improves these clinical markers of MASH. The study is registered at ClinicalTrials.gov (NCT05292911)."

Clinical • Journal • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

COMBINATION THERAPY IN METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS: GLP-1R AGONIST WITH OTHERS (AASLD 2025) - "This study evaluates the efficacy of GLP-1 receptor agonists, specifically Semaglutide, in combination with other agents such as MGL3196, GFT505, Efruxifermin, and Retatrutide in a murine MASH model. The findings indicate that combination therapies involving GLP-1 receptor agonists, particularly Semaglutide, with other pharmacological agents hold promise in the treatment of MASH, offering a potential strategy to address the complex pathophysiology of MASH."

Combination therapy • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Akero Therapeutics, Inc…announced two upcoming oral presentations and a poster presentation at the 76th Annual American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025 taking place November 7-11, 2025, in Washington, DC. (GlobeNewswire) - "The presentations will highlight findings from the 96-week Phase 2b SYMMETRY study evaluating the safety and efficacy of lead product candidate efruxifermin (EFX) in patients with compensated cirrhosis (F4c) due to metabolic dysfunction-associated steatohepatitis (MASH), along with insights from an AI-powered digital analysis of histology data from the 96-week Phase 2b HARMONY study in patients with pre-cirrhotic (F2-F3) MASH."

P2b data • Metabolic Dysfunction-Associated Steatotic Liver Disease

Novo Nordisk to acquire Akero Therapeutics and its promising phase 3 FGF21 analogue to expand MASH portfolio (GlobeNewswire) - "Akero’s fibroblast growth factor 21 (FGF21) analogue efruxifermin (EFX) is a potentially best-in-class treatment for metabolic dysfunction-associated steatohepatitis (MASH)....Under the terms of the agreement, Novo Nordisk will acquire all outstanding shares of Akero’s common stock at a price of 54 USD per share in cash (or aggregated value of 4.7 billion USD) at closing."

M&A • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

AI-POWERED HISTOLOGY ANALYSIS OF HARMONY REVEALS EFRUXIFERMIN-DRIVEN CHANGES IN THE LIVER MICROARCHITECTURE IN F2/F3 MASH (AASLD 2025) - P2 | "Liver Explore analysis of HARMONY revealed improvements in histologic features related to MASH disease activity and fibrosis severity beyond categorical scoring. These results highlight the multimodal and antifibrotic nature of EFX as a MASH therapeutic and corroborate the improvements observed by conventional histology in HARMONY. 1Liver Explore is for research use only."

Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

EFFECTS OF THE FGF21 ANALOGUE EFRUXIFERMIN ON CELL PROLIFERATION AND FIBROGENIC GENE EXPRESSION IN HEPATIC STELLATE CELLS AND LIVER CANCER CELL LINES (AASLD 2025) - "Efruxifermin directly suppressed the proliferation of human HCC cells under lipotoxic conditions. Efruxifermin also directly inhibited growth of human HSCs under profibrotic stimulation, suggesting a context-dependent anti-proliferative effect. Although fibrogenic gene expression was not significantly altered, selective suppression of p-Smad2 suggests partial modulation of TGF-β signaling."

Preclinical • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Liver Cancer • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Oncology • Solid Tumor • ACTA2 • COL1A1 • FGF21 • FGFR1 • KL • SMAD3 • SMAD4 • TGFB1 • TIMP1

EFRUXIFERMIN IMPROVED MARKERS OF PORTAL HYPERTENSION AS EVALUATED BY BAVENO VII CRITERIA IN COMPENSATED CIRRHOSIS DUE TO MASH: RESULTS: FROM A 96-WEEK, PLACEBO-CONTROLLED, PHASE 2B TRIAL (SYMMETRY) (AASLD 2025) - P2 | "Fibrosis improvement with efruxifermin after 96 weeks of treatment was associated with reduced presence of CSPH and lower risk of hepatic decompensation. Accordingly, reversal of fibrosis by efruxifermin in patients with compensated cirrhosis may prevent progression to decompensation and liver-related outcomes. These endpoints are being evaluated in phase 3 trials."

Clinical • P2b data • Cardiovascular • Fibrosis • Hepatology • Immunology • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • Portal Hypertension • FGF21

EFRUXIFERMIN WAS ASSOCIATED WITH IMPROVEMENTS IN MULTIPLE NON-INVASIVE TESTS INDICATIVE OF FIBROSIS REGRESSION IN PARTICIPANTS WITH COMPENSATED CIRRHOSIS DUE TO MASH (SYMMETRY) (AASLD 2025) - P2 | "The high level of concordance between NITs, particularly for the 50-mg dose, highlights the consistent anti-fibrotic effect of efruxifermin. The combination of LSM and ELF response provided increased confidence in the ability to effectively monitor effects of efruxifermin."

Non-invasive • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis

Akero Therapeutics Presents Week 96 Results from Phase 2b SYMMETRY Clinical Trial of Efruxifermin in Patients with Compensated Cirrhosis Caused by MASH Showing Fibrosis Improvement without Worsening of MASH at the EASL Congress 2025 (GlobeNewswire) - P2b | N=200 | Symmetry (NCT05039450) | Sponsor: Akero Therapeutics, Inc | "In the pre-specified analysis of patients with baseline and week 96 biopsies (N=134), 39% of patients treated with EFX 50mg had fibrosis improvement compared to 15% of placebo-treated patients (p=0.009). In the ITT population (N=181), with missing week 96 biopsies treated as non-responders, 29% of patients in the EFX 50mg group experienced this improvement, compared to 11% for placebo (p=0.031)....The primary endpoint of the SYMMETRY study was ≥1 stage fibrosis improvement with no worsening of MASH at Week 36. A numerical improvement was observed in the EFX groups vs. placebo at Week 36 but the differences were not statistically significant."

P2b data • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis

Safety and efficacy of efruxifermin in metabolic dysfunction-associated steatohepatitis: A systematic review. (PubMed, World J Gastrointest Pharmacol Ther) - "EFX demonstrates promising dual efficacy on liver histology and metabolic markers in MASH. However, gastrointestinal side effects and the need for parenteral administration require caution. Long-term data are still necessary to fully evaluate safety and long-term effectiveness."

Journal • Dermatology • Fatigue • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Pain • FGF21

Efruxifermin in Compensated Liver Cirrhosis Caused by MASH. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis

Efruxifermin in Compensated Liver Cirrhosis Caused by MASH. (PubMed, N Engl J Med) - No abstract available

Journal • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis

Positive longer-term results for efruxifermin in MASH. (PubMed, Nat Rev Gastroenterol Hepatol) - No abstract available

Journal • Metabolic Dysfunction-Associated Steatohepatitis

Akero Therapeutics Announces Lancet Publication of the Phase 2b HARMONY Clinical Trial Demonstrating 96 Weeks Treatment with EFX Reduced Liver Fibrosis in Patients with Pre-cirrhotic MASH (GlobeNewswire) - "Continued treatment with EFX from 24 to 96 weeks resulted in more participants exhibiting improvements in fibrosis and MASH, such that there was near complete reversal of disease in almost one-third of participants treated with the 50mg dose of EFX....The secondary endpoint of MASH resolution without fibrosis worsening was achieved by 40% of participants receiving 28mg EFX and 37% receiving 50mg EFX in the mITT population at week 96, compared to 19% for placebo (p=0.020 and p=0.039, respectively)."

P2b data • Metabolic Dysfunction-Associated Steatotic Liver Disease

Efruxifermin: one step closer to disease-modifying therapy in fibrotic MASH. (PubMed, Lancet) - No abstract available

Journal • Fibrosis • Metabolic Dysfunction-Associated Steatohepatitis