--- title: "Efruxifermin (EFX): The Fc-FGF21 Fusion Betting It Can Reverse MASH Cirrhosis (July 12, 2026) | PepTracker Pro Blog" description: "The incretins own the obesity headlines, but the liver has its own race - and it is between two FGF21 analogs. Efruxifermin (EFX) is Akero's bivalent Fc-FGF21 fusion protein, dosed once weekly, and its ambition is bigger than cutting liver fat: in Phase 2b it improved fibrosis in three-quarters of pre-cirrhotic MASH patients and reversed compensated cirrhosis in roughly two of five. Here is how the drug is built, what the HARMONY and SYMMETRY data show, and how it stacks up against pegozafermin as the Phase 3 SYNCHRONY program reads out." lang: en json-ld: | [ { "@context": "https://schema.org", "@type": "Organization", "name": "PepTracker Pro", "url": "https://peptrackerpro.com", "logo": "https://peptrackerpro.com/favicon.png", "description": "Evidence-based educational resource dedicated to improving peptide research literacy.", "contactPoint": { "@type": "ContactPoint", "email": "hello@peptrackerpro.com", "contactType": "customer support" }, "sameAs": [] }, { "@context": "https://schema.org", "@type": "Article", "headline": "Efruxifermin (EFX): The Fc-FGF21 Fusion Betting It Can Reverse MASH Cirrhosis (July 12, 2026)", "description": "The incretins own the obesity headlines, but the liver has its own race - and it is between two FGF21 analogs. Efruxifermin (EFX) is Akero's bivalent Fc-FGF21 fusion protein, dosed once weekly, and its ambition is bigger than cutting liver fat: in Phase 2b it improved fibrosis in three-quarters of pre-cirrhotic MASH patients and reversed compensated cirrhosis in roughly two of five. Here is how the drug is built, what the HARMONY and SYMMETRY data show, and how it stacks up against pegozafermin as the Phase 3 SYNCHRONY program reads out.", "datePublished": "2026-07-12", "dateModified": "2026-07-12", "author": { "@type": "Organization", "name": "PepTracker Pro Research Team", "url": "https://peptrackerpro.com" }, "publisher": { "@type": "Organization", "name": "PepTracker Pro", "logo": { "@type": "ImageObject", "url": "https://peptrackerpro.com/favicon.png" } }, "mainEntityOfPage": { "@type": "WebPage", "@id": "https://peptrackerpro.com/blog/efruxifermin-efx-akr-001-akero-fc-fgf21-fusion-mash-cirrhosis-reversal-synchrony-july-12-2026" } }, { "@context": "https://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": 1, "name": "Home", "item": "https://peptrackerpro.com" }, { "@type": "ListItem", "position": 2, "name": "Blog", "item": "https://peptrackerpro.com/blog" }, { "@type": "ListItem", "position": 3, "name": "Efruxifermin (EFX): The Fc-FGF21 Fusion Betting It Can Reverse MASH Cirrhosis (July 12, 2026)", "item": "https://peptrackerpro.com/blog/efruxifermin-efx-akr-001-akero-fc-fgf21-fusion-mash-cirrhosis-reversal-synchrony-july-12-2026" } ] } ] --- [Skip to main content](#main) **Educational information only.** This site does not provide medical advice. [Read full disclaimer](/disclaimer) [PepTracker Pro](/) [Home](/)[Peptides](/peptides)[Compare](/compare)[Glossary](/glossary)[Blog](/blog)[Calculators](/calculators)[Start Here](/start) [Open the App](https://app.peptrackerpro.com) [Blog](/blog)/ Efruxifermin (EFX): The Fc-FGF21 Fusion Betting It Can Reverse MASH Cirrhosis (July 12, 2026) Research & Compounds Research & Compounds # Efruxifermin (EFX): The Fc-FGF21 Fusion Betting It Can Reverse MASH Cirrhosis (July 12, 2026) PepTracker Pro Research Team July 12, 2026 8 min read ## Table of Contents - [A liver hormone, engineered twice over](#section-0) - [How it differs from pegozafermin](#section-1) - [HARMONY: fibrosis improvement in pre-cirrhotic MASH](#section-2) - [SYMMETRY: aiming at cirrhosis itself](#section-3) - [The Phase 3 SYNCHRONY program](#section-4) - [Safety and how to read it](#section-5) - [The bottom line](#section-6) ## A liver hormone, engineered twice over Fibroblast growth factor 21 (FGF21) is one of the body's own metabolic regulators. Released mainly by the liver under fasting and metabolic stress, it tells the liver, fat tissue, and brain to burn fat, sharpen insulin sensitivity, lower blood triglycerides, and quiet liver inflammation and scarring. That makes it an almost ideal target for metabolic dysfunction-associated steatohepatitis (MASH, the condition formerly called NASH) - the fibrosing form of fatty liver disease that can progress to cirrhosis. The catch is that native FGF21 is cleared within hours. Efruxifermin (EFX) is Akero Therapeutics' answer: a bivalent Fc-FGF21 fusion protein, in which two engineered FGF21 sequences are fused to a human IgG1 Fc domain. The Fc scaffold stabilizes the molecule and slows its clearance enough for once-weekly subcutaneous dosing, while point mutations keep it a potent agonist at the FGF receptors (FGFR1c/2c/3c) and their co-receptor, beta-Klotho. ## How it differs from pegozafermin Efruxifermin and pegozafermin are the two most advanced FGF21 analogs, and they solve the same half-life problem in different ways. Pegozafermin (BIO89-100, now a Roche asset) uses site-specific glycoPEGylation - a PEG chain attached via a glycan linker. Efruxifermin uses Fc fusion, borrowing the same trick that gives antibodies their long circulating life. Both aim at the identical biology, so the interesting question is not mechanism but depth and breadth of effect: how much fibrosis regression each delivers, how they are tolerated, and - increasingly - whether they can help patients whose disease has already advanced to cirrhosis. Efruxifermin originated at Amgen as AMG 876 before Akero took it forward. ## HARMONY: fibrosis improvement in pre-cirrhotic MASH The 96-week Phase 2b HARMONY trial enrolled adults with biopsy-confirmed F2-F3 (pre-cirrhotic) MASH across 41 US centers and randomized them to once-weekly efruxifermin 28 mg, 50 mg, or placebo. By week 96, the share of patients achieving at least a one-stage improvement in fibrosis without worsening of MASH climbed to about 75% on 50 mg and 46% on 28 mg, versus 24% on placebo - with near-complete disease reversal in roughly a third of the 50 mg group. The full results were published in The Lancet in August 2025 and are among the strongest antifibrotic signals reported for any MASH candidate at this stage. ## SYMMETRY: aiming at cirrhosis itself Where efruxifermin has set itself apart is compensated (F4) cirrhosis - the hardest, later stage of MASH, where reversing scarring is far more ambitious. In the Phase 2b SYMMETRY trial, about 39% of patients on 50 mg who had paired week-96 biopsies showed reversal of cirrhosis (a drop to F3 or better) without worsening of MASH, versus 15% on placebo (p=0.009); in the more conservative intent-to-treat analysis that counted missing biopsies as failures, the figure was about 29%. Those data, published in the New England Journal of Medicine, underpin efruxifermin's FDA Breakthrough Therapy designation and its dedicated Phase 3 cirrhosis trial. ## The Phase 3 SYNCHRONY program Efruxifermin's pivotal program spans the full fibrosis spectrum through three trials. SYNCHRONY Histology tests biopsy-defined non-cirrhotic F2-F3 MASH. SYNCHRONY Outcomes, initiated in June 2024, tests compensated F4 cirrhosis with clinical endpoints. SYNCHRONY Real-World enrolled roughly 601 patients with non-invasively diagnosed MASH or MASLD (F1-F4) on once-weekly 50 mg versus placebo, focused on safety and tolerability; its double-blind portion has completed enrollment, with results anticipated in 2026. Together they are designed to convert the Phase 2b promise into the fibrosis, resolution, and outcomes evidence regulators require. ## Safety and how to read it Across trials, the most common adverse events with efruxifermin have been mild-to-moderate, transient gastrointestinal effects - diarrhea, nausea - along with increased appetite and injection-site reactions. As with the whole FGF21 class, effects on bone-turnover markers and other parameters continue to be monitored, and long-term safety will only be settled by the larger, longer Phase 3 dataset. It is worth stressing what efruxifermin is not: it is a liver-disease drug, not an obesity or weight-loss therapy, and it should not be conflated with the GLP-1/GIP incretins that dominate the metabolic headlines. ## The bottom line Efruxifermin is one of two front-runners in a genuine race to drug the FGF21 pathway for MASH, and the one that has pushed hardest into established cirrhosis. Its Fc-FGF21 fusion design is a clean contrast with pegozafermin's glycoPEGylation, and the Phase 3 SYNCHRONY readouts - especially in cirrhosis - are widely viewed as a bellwether for whether FGF21 analogs can deliver durable fibrosis reversal. As always on PepTracker Pro: efruxifermin is investigational, is not available by prescription, and anything sold online under its name is not the clinical drug. Ready to track your peptide research? 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Every article is reviewed for accuracy against peer-reviewed sources and updated as new evidence emerges. ## Citations 1. \[1\] Safety and efficacy of once-weekly efruxifermin versus placebo in MASH (HARMONY): 96-week Phase 2b results - The Lancet (Aug 2025) [Source](https://www.thelancet.com/journals/lancet/article/PIIS0140-6736\(25\)01073-6/abstract) 2. \[2\] Efruxifermin in Compensated Liver Cirrhosis Caused by MASH (SYMMETRY) - NEJM [Source](https://www.nejm.org/doi/full/10.1056/NEJMoa2502242) 3. \[3\] Akero Therapeutics Completes Enrollment of the Double-Blind Portion of the Phase 3 SYNCHRONY Real-World Study [Source](https://ir.akerotx.com/news-releases/news-release-details/akero-therapeutics-completes-enrollment-double-blind-portion/) 4. \[4\] Akero Therapeutics Announces Initiation of Phase 3 SYNCHRONY Outcomes Trial in Compensated Cirrhosis (F4) Due to MASH [Source](https://www.biospace.com/akero-therapeutics-announces-initiation-of-phase-3-synchrony-outcomes-trial-of-efruxifermin-in-patients-with-compensated-cirrhosis-f4-due-to-mash) 5. \[5\] Efruxifermin for MASH - Akero Therapeutics (Fc-FGF21 fusion protein overview) [Source](https://akerotx.com/efruxifermin/) **Disclaimer:** This article is for educational purposes only and does not constitute medical advice. Always consult a licensed healthcare provider. [Read full research disclaimer →](/research-disclaimer) ## Related Articles [![Peptide Guides cover image](/assets/blog-peptide-guides-BQE1jAYz.jpg)](/blog/glp-1-peptides-explained) Peptide Guides [ ### GLP-1 Peptides Explained: Semaglutide, Tirzepatide, and Beyond ](/blog/glp-1-peptides-explained) A comprehensive guide to GLP-1 receptor agonists — how they work, what sets them apart, and where the science is heading. 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Here's how the drug works, what the data show, and how it fits alongside efruxifermin and the incretin-based MASH contenders. PepTracker Pro Team July 10, 2026 8 min read pegozaferminBIO89-100FGF21 [Read](/blog/pegozafermin-bio89-100-glycopegylated-fgf21-analog-mash-fibrosis-roche-89bio-july-10-2026) [PepTracker Pro](/) Educational peptide information and research tracking tools. Not medical advice. #### Explore - [Peptide Directory](/peptides) - [Compare Peptides](/compare) - [Glossary](/glossary) - [Benefits](/benefits/sleep) #### Learn - [Blog](/blog) - [Calculators](/calculators) - [Start Here](/start) - [About](/about) #### Legal - [Editorial Policy](/editorial-policy) - [Research Disclaimer](/research-disclaimer) - [Disclaimer](/disclaimer) - [Privacy Policy](/privacy) - [Terms of Service](/terms) - [Contact](/contact) © 2026 PepTracker Pro. Educational purposes only. Not medical advice. Always consult a licensed healthcare provider.