Once-Monthly Efimosfermin Improves Fibrosis Markers in Phase 2 MASH Study

Once-monthly efimosfermin alfa improved noninvasive markers of fibrosis and reduced liver fat through 52 weeks in adults with metabolic dysfunction–associated steatohepatitis (MASH) and moderate to advanced fibrosis or compensated cirrhosis (F2–F4), according to an open-label phase 2 cohort presented at The Liver Meeting 2026 in Denver, Colorado.¹

Mazen Noureddin, MD, MHSc, of Houston Methodist Hospital and Houston Research Institute, and colleagues reported reductions in liver stiffness, Enhanced Liver Fibrosis (ELF) score, and type III collagen pro-peptide (PRO-C3) with both the 225 mg and 300 mg doses and across fibrosis stages. No treatment-related serious adverse events were reported.¹ The investigators concluded the findings support continued evaluation of patients with advanced fibrosis and compensated cirrhosis in phase 3 trials.

Efimosfermin is an investigational, long-acting fibroblast growth factor 21 (FGF21) analog administered by subcutaneous injection every 4 weeks. In the randomized, double-blind, placebo-controlled portion of the same phase 2 program (NCT04880031), 84 adults with biopsy-confirmed MASH and F2 or F3 fibrosis received efimosfermin 300 mg (n = 43) or placebo (n = 41) for 24 weeks.² Adverse events occurred in 67% of participants receiving efimosfermin and 55% of those receiving placebo; the most frequent were gastrointestinal events, which were transient and occurred within the first few weeks of treatment.² Those results were published in The Lancet in February 2026.

In the biopsy analysis set of that trial, 45.2% of patients receiving efimosfermin achieved at least 1-stage fibrosis improvement without worsening of MASH, compared with 20.6% receiving placebo (P = .038). MASH resolution without worsening of fibrosis occurred in 67.7% vs 29.4%, respectively (P = .002).³ GSK agreed to acquire efimosfermin from Boston Pharmaceuticals in May 2025 for $1.2 billion upfront, with up to $800 million in additional success-based milestone payments.⁴

Where Does Efimosfermin Fit in the MASH Treatment Landscape?

In 2023, a multisociety Delphi consensus replaced the terms nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) with metabolic dysfunction–associated steatotic liver disease (MASLD) and MASH. The new definition requires the presence of at least 1 of 5 cardiometabolic risk factors, reflecting the disease's close ties to obesity and type 2 diabetes.⁵

The burden is substantial and growing. A 2023 systematic review estimated the global prevalence of NAFLD at 30.1%, rising from 25.3% in 1990–2006 to 38.2% in 2016–2019.⁶ When the US Food and Drug Administration (FDA) granted accelerated approval to resmetirom (Rezdiffra) in March 2024, the first therapy approved for the disease, the agency cited an estimate that approximately 6 million to 8 million people in the US have NASH with moderate to advanced fibrosis.⁷

In August 2025, the FDA granted accelerated approval to semaglutide 2.4 mg for adults with MASH and moderate to advanced fibrosis, based on part 1 of the phase 3 ESSENCE trial.⁸ Both approvals are limited to patients with noncirrhotic disease, leaving compensated cirrhosis as the population in which efimosfermin's current development program is most differentiated.⁷,⁸

Who Was Included in the F2–F4 Cohort?

This analysis evaluated a separate cohort of the phase 2 study. Eligible participants were willing and able to undergo liver biopsy and had a body mass index of at least 25, a magnetic resonance imaging–proton density fat fraction (MRI-PDFF) of at least 8%, a vibration-controlled transient elastography liver stiffness measurement (LSM) between 12.0 and 25.0 kPa, and an ELF score of at least 9.8. Participants with F1 fibrosis at baseline were excluded.¹

In total, 24 participants had F2 or F3 fibrosis (225 mg, n = 13; 300 mg, n = 11) and 15 had F4 fibrosis (225 mg, n = 7; 300 mg, n = 8) at baseline. Mean age was 60.6 years, and 51.3% of participants were female. Investigators assessed changes in MRI-PDFF, LSM, ELF score, PRO-C3, pharmacokinetics, and safety through 52 weeks.¹

How Did Liver Fat and Fibrosis Markers Change Through 52 Weeks?

Reductions in liver fat were greater with the 300 mg dose than with 225 mg. Among participants receiving 300 mg, mean (SD) reductions in MRI-PDFF from baseline were 58.5% (43.3; n = 7) in those with F2/F3 fibrosis and 71.1% (13.4; n = 6) in those with F4 fibrosis.¹ The abstract did not report MRI-PDFF values for the 225 mg groups.

Changes in LSM were similar across fibrosis stages and doses. Mean (SD) changes from baseline were −33.6% (13.6; n = 11) with 225 mg and −42.6% (11.6; n = 7) with 300 mg in participants with F2/F3 fibrosis, and −48.5% (11.7; n = 2) with 225 mg and −20.7% (10.4; n = 7) with 300 mg in participants with F4 fibrosis.¹

ELF scores followed a similar pattern. Mean (SD) changes were −0.5 (0.665; n = 11) and −0.843 (0.789; n = 7) with 225 mg and 300 mg, respectively, in F2/F3 fibrosis, and −0.533 (0.603; n = 3) and −0.729 (0.81; n = 7) in F4 fibrosis.¹

PRO-C3, a serum marker of fibrogenesis, decreased by a mean (SD) of 19.5% (25.6; n = 11) with 225 mg and 24.8% (27.3; n = 7) with 300 mg in participants with F2/F3 fibrosis. In those with F4 fibrosis, mean reductions were 21.8% (32.3; n = 3) and 23.5% (14.1; n = 7), respectively.¹

Pharmacokinetics were similar between participants with F2/F3 and F4 fibrosis at the same dose, with higher efimosfermin exposure observed at 300 mg.¹

What Did the Safety Data Show in Compensated Cirrhosis?

No participants with F2/F3 fibrosis experienced a serious adverse event. Among those with F4 fibrosis, 20% (n = 3) had a serious adverse event, none of which were considered related to study treatment.¹ The abstract did not report the types of adverse events observed, gastrointestinal event rates, or discontinuations.

What Are the Limitations of the 52-Week Findings?

The cohort was open label and had no placebo comparator, so changes from baseline cannot be attributed to efimosfermin with the same confidence as randomized results. The sample was small, and the number of participants with evaluable 52-week data was lower than the number enrolled in several groups; for example, LSM results in the F4 225 mg group reflect 2 of 7 participants. The abstract did not report P values, CIs, or histologic outcomes, and noninvasive tests are surrogate markers that have not been validated as substitutes for clinical outcomes in this setting.¹

The findings are from a conference abstract and have not been published in a peer-reviewed journal.

What Comes Next for Efimosfermin?

GSK is evaluating efimosfermin in phase 3 trials, including NEBULA-1 (NCT07701993), a pivotal placebo-controlled study in adults with compensated cirrhosis due to MASH. The trial began in July 2026 and is recruiting, with primary completion estimated for 2033.⁹

Editor's Note: Several study authors are employees of GSK or Boston Pharmaceuticals, according to the abstract's author affiliations.

References

1. Noureddin M, Loomba R, Lennie J, et al. Once-monthly efimosfermin alfa improves non-invasive markers of fibrosis with an acceptable safety profile in participants with metabolic dysfunction-associated steatohepatitis with moderate to advanced fibrosis or compensated cirrhosis (F2–4): results up to 52 weeks from an open-label, phase 2 study. Abstract 2299. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.
2. Noureddin M, Kowdley KV, Odrljin T, et al. Efimosfermin alfa (BOS-580) once per month in people with metabolic dysfunction-associated steatohepatitis with F2 or F3 fibrosis: results from a 24-week, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2026;407(10530):794-804. doi:10.1016/S0140-6736(25)02276-7
3. Once-monthly efimosfermin alfa shows promise for MASH in phase 2 study. HCPLive. Published May 5, 2025. Accessed November 6, 2026. https://www.hcplive.com/view/once-monthly-efimosfermin-alfa-shows-promise-mash-in-phase-2-study
4. Cleary Gottlieb. GSK to acquire efimosfermin from Boston Pharmaceuticals. Published May 14, 2025. Accessed November 6, 2026. https://www.clearygottlieb.com/news-and-insights/news-listing/gsk-to-acquire-efimosfermin-from-boston-pharmaceuticals
5. Rinella ME, Lazarus JV, Ratziu V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. J Hepatol. 2023;79(6):1542-1556. doi:10.1016/j.jhep.2023.06.003
6. Younossi ZM, Golabi P, Paik JM, et al. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77:1335-1347.
7. US Food and Drug Administration. FDA approves first treatment for patients with liver scarring due to fatty liver disease. Published March 14, 2024. Accessed November 6, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease
8. Novo Nordisk. Wegovy approved in the US for the treatment of MASH. Published August 15, 2025. Accessed November 6, 2026. https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=167078
9. A pivotal clinical study to investigate the safety and efficacy of efimosfermin compared with placebo in adult participants with compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH) (NEBULA-1). ClinicalTrials.gov identifier: NCT07701993. Updated September 30, 2026. Accessed November 6, 2026. https://clinicaltrials.gov/study/NCT07701993