In clinical trials, efruxifermin (Akero Therapeutics) demonstrated its ability to help patients who have metabolic dysfunction-associated steatohepatitis (MASH), a type of liver disease. Efruxifermin helped reverse scarring of the liver without worsening the patients’ condition.1
Efruxifermin is an experimental drug currently undergoing investigation for its efficacy in patients with severe scarring or cirrhosis because of MASH.1 It has been engineered to mimic the biological activity of a fibroblast growth factor 21 (FGF21), which can regulate multiple metabolic pathways and cellular processes. The investigational drug delivers sustained and balanced signaling through the FGF21 receptors in liver and adipose tissue, addressing all core drivers of disease progression, therefore, showing its potential to treat MASH.2,3
About the Trials
1. SYNCHRONY Histology
- Trial Name: A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
- ClinicalTrials.gov ID: NCT06215716
- Sponsor: Akero Therapeutics, Inc
- Completion Date (Estimated): November 2032
2. SYNCHRONY Real-World
- Trial Name: A Study Evaluating Efruxifermin in Subjects With Non-invasively Diagnosed Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Nonalcoholic Fatty Liver Disease (NAFLD)/Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
- ClinicalTrials.gov ID: NCT06161571
- Sponsor: Akero Therapeutics, Inc
- Completion Date (Estimated): October 2026
3. SYNCHRONY Outcomes
- Trial Name: A Study Evaluating Efruxifermin in Subjects with Compensated Cirrhosis Due to NASH/MASH
- ClinicalTrials.gov ID: NCT06528314
- Sponsor: Akero Therapeutics, Inc
- Completion Date (Estimated): October 2029
4. HARMONY
- Trial Name: A Study of Efruxifermin in Non-Cirrhotic Subjects With Histologically Confirmed Nonalcoholic Steatohepatitis (NASH) (Harmony)
- ClinicalTrials.gov ID: NCT04767529
- Sponsor: Akero Therapeutics, Inc
- Completion Date (Estimated): May 2024
Currently, efruxifermin is being evaluated in the phase 3 SYNCHRONY program3, which consists of the 3 multicenter, randomized, double-blind, placebo-controlled clinical trials SYNCHRONY Histology (NCT06215716)4, SYNCHONY Real-World (NCT06161571)5, and SYNCHRONY Outcomes (NCT06528314)6. The trials are evaluating the following: the efficacy and safety of efruxifermin in patients with biopsy-confirmed pre-cirrhotic MASH, fibrosis stages 2 and 3 (SYNCHRONY Histology); the safety and tolerability of efruxifermin in patients with non-invasively diagnosed MASH or metabolic dysfunction-associated steatotic liver disease (MASLD), fibrosis stages 1 through 4 (SYNCHRONY Real-World); and efruxifermin for the treatment of compensated cirrhosis because of MASH, fibrosis stage 4 (SYNCHRONY Outcomes).3
In the randomized, double-blind, placebo-controlled phase 2b HARMONY trial (NCT04767529)7, investigators assessed the efficacy and safety of efruxifermin in patients with pre-cirrhotic MASH and stage 2 or 3 fibrosis. The trial met its primary end point and demonstrated that, compared with placebo, 28- and 50-mg doses of efruxifermin did not worsen patients’ MASH following 24 weeks of treatment (28 mg: 39%; 50 mg: 41%; and placebo: 20%).3,7
More patients experienced at least a 1-stage improvement in fibrosis without worsening of MASH in both dose groups (28 mg: 46%; 50 mg: 75%) compared with placebo (24%). Additionally, approximately 31% and 36% of patients in the 28-mg and 50-mg dose groups, respectively, experienced a 2-stage improvement in fibrosis without their disease worsening, which is over 10-fold compared with placebo (3%). Those who had stage 3 fibrosis were more likely to experience at least a 1-stage improvement in fibrosis when treated with efruxifermin (28 mg: 40%; 50 mg: 68%) compared with placebo (14%). The investigational treatment had also met secondary and exploratory end points through 96 weeks of treamtent.3
“Notwithstanding inherent limitations in making cross-trial comparisons, the statistically significant results for [at least] 1- and 2-stage fibrosis improvement and no worsening of MASH observed for 50 mg [of] efruxifermin at week 96 are the largest response rates reported publicly to date for these end points in any MASH population,” Stephen Harrison, MD, medical director of Pinnacle Clinical Research, said in a news release.8
Further, efruxifermin was shown to be generally well-tolerated. A total of 15 serious adverse events (AEs) were reported, and these were balanced across dose groups. In both dose groups, the most frequent AEs were grades 1 or 2 gastrointestinal complications (eg, diarrhea, nausea, and increased appetite), which were considered brief. Three participants treated with efruxifermin (28 mg: n = 2; 50 mg: n = 1) discontinued their treatment because of AEs between weeks 24 and 96. During the trial, no deaths were reported.8
REFERENCES
1. Reuters. Akero soars as drug shows it reverses scarring in liver disease patients. News release. January 27, 2025. Accessed January 28, 2025. https://www.reuters.com/business/healthcare-pharmaceuticals/akero-shares-double-after-preliminary-results-mid-stage-trial-liver-disease-drug-2025-01-27/
2. Akero Therapeutics. Efruxifermin (EFX). Accessed January 28, 2025. https://akerotx.com/efruxifermin/
3. Akero Therapeutics. Clinical Trials Overview. Accessed January 28, 2025. https://akerotx.com/clinical-trials/
4. A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis. ClinicalTrials.gov identifier: NCT06215716. Updated January 23, 2025. Accessed January 28, 2025. https://www.clinicaltrials.gov/study/NCT06215716
5. A Study Evaluating Efruxifermin in Subjects With Non-invasively Diagnosed Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Nonalcoholic Fatty Liver Disease (NAFLD)/Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). ClinicalTrials.gov identifier: NCT06161571. Updated January 17 2025. Accessed January 28, 2025. https://www.clinicaltrials.gov/study/NCT06161571
6. A Study Evaluating Efruxifermin in Subjects with Compensated Cirrhosis Due to NASH/MASH. ClinicalTrials.gov identifier: NCT06528314. Updated December 16, 2024. Accessed January 28, 2025. https://clinicaltrials.gov/study/NCT06528314
7. A Study of Efruxifermin in Non-Cirrhotic Subjects With Histologically Confirmed Nonalcoholic Steatohepatitis (NASH) (Harmony). ClinicalTrials.gov identifier: NCT04767529. Updated April 21, 2023. Accessed January 28, 2025. https://clinicaltrials.gov/study/NCT04767529
8. Akero Therapeutics. Akero Therapeutics Reports Statistically Significant Histological Improvements at Week 96 in Phase 2b HARMONY Study. News release. March 4, 2024. Accessed January 28, 2025. https://ir.akerotx.com/news-releases/news-release-details/akero-therapeutics-reports-statistically-significant
