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.

# 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 *The Lancet 2026* Articles 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 Mazen Noureddin, Kris V Kowdley, Tatjana Odrljin, Gerard Bain, Jeff Zhao, Brenda Jeglinski, Margaret James Koziel, Rohit Loomba Summary Lancet 2026; 407: 794–804 Background The growing prevalence of metabolic dysfunction-associated steatohepatitis (MASH) underscores the Published Online unmet need for eective and safe liver-targeted therapies to prevent fibrosis and disease progression. The aim of this February 5, 2026 study was to evaluate the ecacy and safety of efimosfermin alfa (henceforth referred to as efimosfermin, formerly https://doi.org/10.1016/ BOS-580), an FGF21 analogue taken once per month, in patients with MASH and moderate or advanced fibrosis. S0140-6736(25)02276-7 This online publication has Methods This 24-week, randomised, double-blind, placebo-controlled, phase 2 trial evaluated the safety and ecacy of been corrected. The corrected version first appeared at efimosfermin in participants aged 18–75 years with a BMI of at least 27 kg/m² and MASH and F2 or F3 fibrosis thelancet.com on May 7, 2026 present on a diagnostic liver biopsy done either during screening or within 6 months before the first day of dosing, See Comment page 739 and total activity Nonalcoholic Fatty Liver Disease Activity Score (NAS) of at least 4 with a minimum score of 1 point Department of Medicine, for all three NAS components (steatosis, hepatocyte ballooning, and lobular inflammation). The trial was conducted Houston Methodist Hospital, at 34 clinical research study sites in the USA. Participants were randomly assigned 1:1 to efimosfermin 300 mg or Houston, TX, USA placebo administered by subcutaneous injection every 4 weeks (Q4W) over 24 weeks, stratified by MASH fibrosis (Prof M Noureddin MD); stage (F2 vs F3 stage). Participants, investigators, and those assessing outcomes were masked to group assignment. Houston Research Institute, Houston, TX, USA The primary endpoint was safety and tolerability (ie, treatment-emergent adverse events, changes from baseline to (Prof M Noureddin MD); Liver week 24 in blood pressure and heart rate, and the incidence of grade 3 and grade 4 laboratory abnormalities at Institute Northwest, week 24), analysed in all participants who received at least one dose. This trial is registered with ClinicalTrials.gov Elson S Floyd College of (NCT04880031) and was completed on Sept 18, 2024. Medicine, Seattle, WA, USA (Prof K V Kowdley MD); Boston Pharmaceuticals, Cambridge, Findings Between May 4, 2023, and March 22, 2024, of 1171 participants screened, 84 participants were randomly MA, USA (T Odrljin MD, assigned to efimosfermin 300 mg Q4W (n=43) or placebo (n=41); 44 (52%) were female and 40 (48%) were male. G Bain PhD, J Zhao PhD, 48 (57%) had F2 fibrosis and 36 (43%) had F3 fibrosis; 65 had evaluable week-24 biopsy results. All 43 in the efimosfermin B Jeglinski BS, M J Koziel MD); University of California, group and 40 of 41 participants in the placebo group received at least one dose. Adverse events were reported in San Diego, CA, USA 29 (67%) of 43 participants receiving efimosfermin and 22 (55%) of 40 receiving placebo. The majority of treatment- (Prof R Loomba MD) emergent adverse events were mild (24 [56%] of 43 in the efimosfermin group vs 15 [38%] of 40 in the placebo group) or Correspondence to: moderate (18 [42%] vs 14 [35%]) in severity. Most frequent adverse events were gastrointestinal events, which were Prof Mazen Noureddin, transient and occurred within the first few weeks of treatment. There were no clinically meaningful changes in vital Department of Medicine, Houston Methodist Hospital, signs between treatment and placebo groups, and no clinically significant grade 3 or higher laboratory abnormalities Houston Research Institute, observed for either group. No deaths or adverse events greater than grade 3 were observed during the study. Summit and Pinnacle Clinical Research, Houston, TX 77079, Interpretation In this phase 2 trial, treatment with efimosfermin once per month was generally well tolerated in USA NoureddinMD@ participants with biopsy-confirmed MASH and F2 or F3 fibrosis. These results support the further development of pinnacleresearch.com efimosfermin for treatment of MASH-related fibrosis. Funding Boston Pharmaceuticals and GSK. Copyright © 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. Introduction progresses.4 With scarce treatment options, a crucial Metabolic dysfunction-associated steatohepatitis (MASH) unmet need remains for eective and safe therapeutic is characterised by the accumulation of excess fat in the strategies to manage MASH and mitigate its associated liver, leading to inflammation, hepatocyte injury, and risks.5,6 fibrosis.1,2 The prevalence of MASH is increasing in Fibroblast growth factor 21 (FGF21) is a potential parallel with the rising prevalence of its closely associated treatment for MASH, with pleiotropic biological eects conditions, obesity and type 2 diabetes.2,3 The risk of liver- that regulate metabolism, protect against steatosis, related complications and mortality escalates as fibrosis improve dyslipidaemia, and decrease liver 794 Articles Research in context Evidence before this study moderate-to-advanced fibrosis due to MASH. Long-acting We did a literature review using PubMed between Feb 17, formulations, such as efimosfermin, offer the potential to and Feb 28, 2025, focusing on English-language clinical studies. enhance patient compliance and reduce treatment burden. In Our search included the terms “NASH” or “NAFLD”, given that the present study, participants treated with efimosfermin Medical Subject Headings terms have not yet adopted the 300 mg Q4W reached fibrosis improvement of at least updated metabolic-related terminology, alongside keywords one stage without worsening of MASH, and MASH resolution such as “fibroblast growth factor 21”, “FGF21 analogue”, and without worsening of fibrosis after 24 weeks, with both “FGF21 agonist” and identified 143 articles. FGF21 agonists histological endpoints showing statistically significant have been shown to reduce hepatic steatosis, improve insulin differences versus placebo. Improvements in lipids and sensitivity, and improve metabolic markers of disease. In clinical glycaemic control, including clinically meaningful reductions in trials, FGF21 analogues with balanced agonism across FGFR1c, HbA among those with type 2 diabetes, indicate a broader 1c FGFR2c, and FGFR3c have further shown histological cardiometabolic benefit of efimosfermin beyond its hepatic improvement in fibrosis and metabolic dysfunction-associated effects. Efimosfermin was generally well tolerated over the steatohepatitis (MASH) resolution with beneficial changes in 24-week treatment period. non-invasive markers of liver and cardiometabolic health in Implications of all the available evidence patients with MASH. Efruxifermin, an Fc-fusion FGF21 As the number of individuals affected by MASH continues to analogue, and pegozafermin, a glycopegylated analogue, are rise and treatment options remain scarce, there is a clear unmet among those evaluated in phase 2b trials with either weekly or need for therapies that are well tolerated, reduce treatment biweekly dosing, showing antifibrotic activity within 24 weeks burden, and improve rates of fibrosis regression as a major of treatment in patients with moderate or advanced fibrosis, or determinant of liver-related outcomes. Notably, the histological up to 96 weeks in those with compensated cirrhosis due to and cardiometabolic improvements observed with MASH. Published results from the phase 2a 12-week trial of efimosfermin once-per-month dosing were achieved over a once-per-month efimosfermin in phenotypic MASH reported a relatively short 24-week treatment period, suggesting that favourable safety profile, improvements in indicators of hepatic longer-acting formulations are feasible and might improve and metabolic health, and a significant proportion of patients long-term adherence and reduce patient burden—important who met liver fat reduction thresholds associated with considerations in the management of a serious and chronic histological response. condition such as MASH. Overall, findings from this phase 2 Added value of this study study support the continued development of efimosfermin as a This phase 2 study is the first, to our knowledge, to evaluate a promising therapy for MASH and warrant further investigation once-per-month FGF21 analogue in participants with in phase 3 trials of longer duration. inflammation.7–9 In addition to direct eects on the liver, that has been associated with a higher likelihood of FGF21 increases glucose uptake in adipose tissue, fibrosis regression.14–18 Liver histopathology was further thereby increasing insulin sensitivity.7,10 Efimosfermin evaluated in this 24-week treatment study, which alfa (henceforth referred to as efimosfermin, formerly examined the ecacy and safety of efimosfermin 300 mg BOS-580) is a variant of human FGF21, engineered to once per month in participants with biopsy-confirmed overcome the 2 h half-life of naturally occurring FGF21. MASH and F2–F3 fibrosis. Efimosfermin is fused at its N-terminus to the crystallisable fragment of human IgG1 (IgG1-Fc) and is Methods further stabilised through the introduction of a novel Study design disulphide bond and point mutations that increase This was a phase 2, multicentre, double-blind, randomised, proteolytic resistance. These changes increase its half-life placebo-controlled trial conducted at 34 clinical research to 21 days, which allows for administration once per study sites in the USA (appendix pp 8, 18). Sites were See Online for appendix month, in contrast to other FGF21 MASH treatments selected using predefined criteria, including disease that necessitate more frequent administration.11–13 experience, patient access, and site capabilities, with Efimosfermin was studied in a phase 2a multicentre, feasibility assessed via questionnaire before selection. The randomised, double-blind, placebo-controlled study to study adhered to the principles of the Declaration of evaluate several doses and dosing regimens of Helsinki, International Ethical Guidelines of the Council efimosfermin in participants with phenotypic MASH.14 for International Organizations of Medical Sciences, the The study showed statistically significant improvement Good Clinical Practice guidelines of the International in liver steatosis, with 100% of participants receiving Council for Harmonisation, and applicable laws and efimosfermin 300 mg every 4 weeks (Q4W) reaching at regulations. Study protocols and amendments were least 30% reduction in hepatic fat fraction (HFF), a result approved by one central institutional review board (IRB; Articles Advarra Ethics Committee approval number Procedures MOD02074580). Patients or the public were not involved On the basis of randomisation assignment, participants with clinical trial design and conduct. This trial is registered were treated with efimosfermin 300 mg Q4W or placebo with ClinicalTrials.gov (NCT04880031) and phase 2 part B administered in clinic by subcutaneous injection during (the focus of this Article) was completed on Sept 18, 2024; visits. phase 2 parts C and D are also both completed. During the 24-week treatment period, all participants had a clinic visit during week 1 and Q4W to week 24, and a Participants follow-up visit 4 weeks after the final dose. A liver biopsy Participants were recruited via referral from treating was scheduled for the week 24 visit, with biopsy samples clinicians and from prescreening activities at study sites collected between week 20 and week 28 (inclusive) that included advertising on social media, clinic flyers, considered acceptable for analysis. Two pathologists local health fairs, and community outreach. Eligible provided a simultaneous consensus read with a third participants were aged 18–75 years with a BMI of at least pathologist available to adjudicate, if necessary. The 27 kg/m². Participants were included if histology- assessment of the adjudicator was taken as the final confirmed F2 or F3 stage MASH, according to the Clinical assessment. Pathologists were masked to participants and Research Network in Non-alcoholic Steatohepatitis treatment. A full listing of evaluations done and their classification, was present on a diagnostic liver biopsy scheduling is available in the appendix (p 23). A safety done either during screening or within 6 months before review team, which included members of the research the first day of dosing and total activity Nonalcoholic Fatty team and an independent hepatologist, did the ongoing Liver Disease Activity Score (NAS) was at least 4 with a monitoring of participant safety in a blinded manner minimum score of 1 for all three NAS components during the study. Rescue medications were not used in this (steatosis, hepatocyte ballooning, and lobular study; management of adverse events was done at the inflammation).19 Additional inclusion criteria included discretion of the investigator. One patient in the HFF of at least 8% by MRI-derived proton density fat efimosfermin group had a protocol deviation and was fraction (MRI-PDFF), controlled attenuation parameter required to terminate the study after 29 days due to taking (CAP) score greater than 300 dB/m, liver stiness an exclusionary medication (insulin). measurement of at least 7·0–20·0 kPa based on vibration- controlled transient elastography (VCTE), aspartate Outcomes aminotransferase (AST) of greater than 25 U/L, and a The primary outcome was the safety and tolerability of history or presence of at least two of four components of efimosfermin, based on treatment-emergent adverse metabolic syndrome, comprising obesity or overweight, events, changes from baseline to week 24 in blood dyslipidaemia, type 2 diabetes with elevated glycated pressure and heart rate, and the incidence of grade 3 and haemoglobin A (HbA ), and hypertension. Key exclusion grade 4 laboratory abnormalities at week 24. The 1c 1c criteria were clinical, laboratory, or radiological evidence secondary outcome was assessment of efimosfermin of cirrhosis. Full inclusion and exclusion criteria are listed pharmacokinetics (efimosfermin serum concentration in the appendix (p 19). on day 7, C and area under the curve for one dosing trough Participants’ sex was either self-reported by participants interval at steady state). Exploratory ecacy outcomes or taken from medical records; it was defined on the basis were the proportions of participants reaching at least of a binary categorisation (male or female) that was usually a ≥30%, ≥50%, or ≥70% reduction in HFF compared designated at birth and generally refers to a set of biological with baseline; absolute and relative changes in HFF from attributes that are associated with physical and baseline to weeks 16 and 28 as assessed by MRI-PDFF; physiological features. Race was defined on the basis of the proportion of participants achieving resolution of standard racial categories and was captured via self-report. steatohepatitis (defined as NAS of 0 for ballooning All participants provided written informed consent. and 0–1 for inflammation) without worsening of liver fibrosis at week 24; the proportion achieving at least a Randomisation and masking one-stage improvement in fibrosis (defined as no Investigators at each site were responsible for screening increase in NAS for ballooning or lobular inflammation) and enrolment, with participants randomly assigned 1:1 without worsening of steatohepatitis at week 24; the to efimosfermin or placebo groups via a centralised proportion achieving both resolution of steatohepatitis interactive response system. Patients, site sta who were and at least a one-stage improvement in liver fibrosis at administering the intervention, and those assessing week 24; and the proportion achieving resolution of outcomes were all masked. Masking was achieved using steatohepatitis with an at least 2-point improvement in a random allocation sequence that was programmatically NAS without worsening of liver fibrosis at week 24. generated by an independent biostatistician. Additional exploratory endpoints were continuous Randomisation was stratified by MASH fibrosis stage scoring of NAS components, fibrosis stage, and other (F2 vs F3 stage) as confirmed by central pathology artificial intelligence (AI)-based parameters; changes readers. from baseline in serum Pro-C3, alanine aminotransferase 796 Articles (ALT), AST, AST:ALT ratio, Non-Alcoholic Fatty Liver [BAS]); participants with protocol-defined out-of-window Disease fibrosis score, and fibrosis-4 index; changes in visits (n=2) were not included in this analysis. Post-hoc liver stiness by VCTE LSM; changes in high-sensitivity analyses of histology endpoints were done in the C-reactive protein, IL-6, tumour necrosis factor α, IL-10, intention-to-treat (ITT) population, defined as all IFN-γ, and IL-1β; changes in Enhanced Liver Fibrosis randomly assigned participants who received at least (ELF) and Agile3+ scores; changes in liver fibrosis as one dose (FAS). Participants without biopsy results after measured by magnetic resonance elastography at baseline were considered non-responders. Histological week 28; changes in MCP-1; changes in fasting plasma response was further evaluated post hoc across subgroups glucose, Homeostasis Model Assessment of Insulin of interest for descriptive purposes only. Odds ratios and Resistance (HOMA-IR), C-peptide, glucagon, and corresponding 95% CIs were calculated for each insulin; changes in HbA, bodyweight, waist subgroup to assess consistency of treatment response. 1c circumference, and adiponectin; changes in fasting total Safety endpoints were coded based on the Medical cholesterol, LDL cholesterol, HDL cholesterol, and Dictionary for Regulatory Activities and graded using the triglycerides; changes in serum β-CTX (bone resorption National Cancer Institute’s Common Terminology Criteria biomarker) and bone formation biomarkers (BSAP, for Adverse Events version 5.0 and were summarised by P1NP, and osteocalcin); antidrug antibodies before and system organ class and preferred term. For categorical after baseline over the treatment period and at study end; exploratory endpoints, descriptive statistics were and evaluation of key endpoints in relation to summarised by treatment group, and dierences between efimosfermin concentration and pharmacokinetic efimosfermin and placebo were tested using a parameters. Cochran-Mantel-Haenszel test stratified by baseline A full list of all primary, secondary, and exploratory fibrosis stage. For continuous exploratory endpoints, endpoints are provided in the appendix (p 25). The dierences between efimosfermin and placebo were secondary (pharmacokinetic) outcomes and some tested with an ANCOVA model with change (or percentage exploratory endpoints (eg, the use of AI to assess change) from baseline as the dependent variable and pathology, and the evaluation of key endpoints in relation to efimosfermin concentration and pharmacokinetic parameters) are not reported in this Article, but might be 1171 patients screened reported separately in future work to examine additional aspects of efimosfermin treatment response. 1087 excluded (screen failure) Statistical analysis Because the primary endpoint of the study was safety 84 randomly assigned and tolerability, no formal sample size calculation was required. To ensure sucient power for the ecacy endpoints presented along with the safety findings, the 41 assigned to placebo 43 assigned to efimosfermin 300 mg sample size for this study was calculated assuming a two-sided Fisher’s exact test with alpha of 0·05. These calculations were based on the assumption of an eect 7 discontinued 10 discontinued 3 withdrew 7 withdrew size of 32–36% for the biopsy-driven endpoints assessed 2 lost to follow-up 2 adverse event in this study.13 Considering the dropout rate observed in 1 non-compliance with study drug 1 protocol deviation 1 other phase 2a and the possibility of further attrition due to changes in the study design, we estimated a 20% dropout rate. To ensure sucient power for FAS population FAS population biopsy-related endpoints, we calculated a sample size of 40 received at least 1 dose of study 43 received at least 1 dose of study treatment treatment 80 participants. Participant disposition and baseline characteristics were assessed for all participants who gave informed mFAS population mFAS population consent and were randomly assigned (enrolled analysis 36 valid baseline and ≥1 post-baseline HFF 35 valid baseline and ≥1 post-baseline HFF set [EAS]). All safety analyses and exploratory biomarkers except HFF were assessed for all participants who 34 completed study treatment 33 completed study treatment received at least one dose of the study drug or placebo (full analysis set [FAS]). HFF was assessed for all BAS population BAS population participants in the FAS who had a valid baseline and at 34 post-baseline biopsy between 31 post-baseline biopsy between least one HFF after baseline (modified FAS [mFAS]). week 20 and week 28 week 20 and week 28 Histological endpoints were assessed in all participants in the FAS who had a biopsy at and after baseline that Figure 1: Participant disposition (CONSORT flow diagram) occurred 20–28 weeks from day 1 (biopsy analysis set BAS=biopsy analysis set. FAS=full analysis set. mFAS=modified full analysis set. Articles eects for independent variables of treatment group and review approval of the publication. Boston Pharmaceuticals baseline value in the model. Least-squares means and supplied the study drug. associated 95% CIs are presented. Statistical tests for exploratory endpoints were done at a two-sided type 1 Results error rate of 0·05 with no adjustments for multiplicity. Between May 4, 2023, and March 22, 2024, of Statistical analyses were done using SAS version 9.4 or 1171 participants screened, 84 participants were randomly higher. assigned to efimosfermin 300 mg Q4W (n=43) or placebo (n=41; figure 1). Role of the funding source Participant demographics and baseline clinical The funders of the study, Boston Pharmaceuticals and characteristics in the EAS population were generally GSK, participated in the concept and design of the study, similar among the efimosfermin 300 mg Q4W and data collection, data analysis, and data interpretation, and placebo groups (table 1). Overall, 48 (57%) of 84 participants had stage F2 fibrosis and 36 (43%) of 84 had stage F3 fibrosis at baseline. More than half of participants had Placebo (n=41) Efimosfermin 300 mg Total (N=84) Q4W (n=43) type 2 diabetes and half were on antidiabetic medication. Types of antidiabetic medications taken during the Age, years 54·6 (10·2) 52·9 (11·7) 53·7 (10·9) course of the study are presented in the appendix (p 9). Sex, female* 21 (51%) 23 (53%) 44 (52%) Baseline characteristics were also similar among the Sex, male* 20 (49%) 20 (47%) 40 (48%) efimosfermin 300 mg Q4W and placebo groups in the Ethnicity BAS population (appendix p 10). Hispanic or Latino 34 (83%) 28 (65%) 62 (74%) Overall, adverse events were reported in Not Hispanic or Latino 7 (17%) 15 (35%) 22 (26%) 29 (67%) of 43 participants in the efimosfermin 300 mg Race† Q4W group and 22 (55%) of 40 in the placebo group American Indian or Alaska Native 0 1 (2%) 1 (1%) (appendix p 11). Most treatment-emergent adverse Black or African American 1 (2%) 0 1 (1%) events were mild or moderate in severity. The most White 36 (88%) 40 (93%) 76 (90%) frequent treatment-emergent adverse events were Other 4 (10%) 2 (5%) 6 (7%) gastrointestinal-related events, including nausea, Weight, kg 103·2 (17·6) 106·5 (20·2) 104·9 (18·9) diarrhoea, and vomiting (table 2). No adverse events BMI, kg/m 37·2 (6·0) 37·5 (5·7) 37·3 (5·8) greater than grade 3 or deaths were reported. Most Type 2 diabetes 20 (49%) 28 (65%) 48 (57%) gastrointestinal-related adverse events lasted between HbA 1c , mean percentage (SD) 6·4% (1·1) 6·7% (1·1) 6·6% (1·1) 2 days and 2 months. Liver histology There were two serious adverse events in the study; Fibrosis stage, F2‡ 23 (56%) 25 (58%) 48 (57%) both occurred in the efimosfermin 300 mg group. Fibrosis stage, F3‡ 18 (44%) 18 (42%) 36 (43%) One participant with a medical history of gastro- NAS 5·1 (0·9) 5·1 (0·9) 5·1 (0·9) oesophageal reflux disease reported grade 3 gastritis HFF, mean percentage (SD) 21·2% (6·5) 19·6% (8·3) 20·4% (7·5) (determined not to be treatment related by the study Pro-C3, ng/mL 56·3 (20·7) 49·6 (16·8) 52·9 (19·0) investigator) and one participant reported grade 3 biliary VCTE LSM, kPa 12·1 (3·9) 11·4 (3·0) 11·7 (3·5) colic (recurrent disease, determined to be treatment ALT, IU/L 57·0 (25·3) 63·5 (44·1) 60·3 (36·1) related by the study investigator; table 2). This event was AST, IU/L 43·1 (18·0) 51·4 (37·7) 47·3 (29·9) most likely due to pre-existing chronic cholelithiasis, as Adiponectin, µg/L 4078·3 (2147·6) 4227·9 (2479·4) 4154·0 (2308·5) reported by the investigator. Triglycerides, mmol/L 2·3 (1·4) 1·8 (0·7) 2·0 (1·1) Two (5%) of 83 participants discontinued treatment HDL-C, mmol/L 1·2 (0·3) 1·2 (0·3) 1·2 (0·3) before week 24 because of adverse events. LDL-C, mmol/L 2·9 (0·9) 2·7 (1·0) 2·8 (1·0) One discontinuation was due to grade 2 abdominal pain, Total cholesterol, mmol/L 5·1 (1·2) 4·7 (1·1) 4·9 (1·1) nausea, and vomiting, whereas the other was due to Concomitant medications grade 1 dehydration. Both events occurred in the Antihypertensive 27 (66%) 17 (40%) 44 (53%) efimosfermin 300 mg group and were considered to be Antidiabetic 18 (44%) 24 (56%) 42 (50%) related to efimosfermin by the study investigator. Lipid lowering 13 (32%) 14 (33%) 27 (32%) No notable changes were observed in standard safety laboratory assessments, and no clinically relevant changes Data are mean (SD) or n (%) unless otherwise stated. ALT=alanine aminotransferase. AST=aspartate aminotransferase. were detected in vital signs and electrocardiograms EAS=enrolled analysis set. HbA=glycated haemoglobin. HFF=hepatic fat fraction. Pro-C3=N-terminal propeptide of 1c type 3 collagen. NAS=Nonalcoholic Fatty Liver Disease Activity Score. Q4W=every 4 weeks. VCTE LSM=vibration- (appendix p 14). There were no clinically significant controlled transient elastography liver stiffness measurement. *Sex was defined on the basis of a binary categorisation grade 3 or higher laboratory abnormalities observed for (male or female) that is usually designated at birth and generally refers to a set of biological attributes that are either group. No clinically meaningful changes were associated with physical and physiological features. †Race was defined on the basis of standard racial categories and was captured via self-report. ‡All participants were either fibrosis stage 2 (F2) or stage 3 (F3). observed in the liver function (albumin and total bilirubin) and haemostasis (platelets) biomarkers from Table 1: Participant demographics and baseline clinical characteristics (EAS population) baseline to week 24 (appendix p 15). 798 Articles No clinically meaningful dierences in bone analysis of the FAS population also showed no statistically biomarkers were observed between placebo and significant dierences in the change in β-CTX values efimosfermin 300 mg Q4W at week 24 (appendix p 16) from baseline through week 24 between the efimosfermin and no fractures were reported in the study. A post-hoc and placebo groups: week 24 mean values of 351·5 pg/mL (SD 143·1) for placebo and 394·1 pg/mL (152·5) for efimosfermin, with a least-squares mean dierence of 61·4 pg/mL (95% CI –9·4 to 132·1; p=0·088). β-CTX values in female participants who had had the menopause remained within the reference range until the end of the study (baseline median value 286 pg/mL [IQR 91]; end of study median value 372 pg/mL [186]). A post-hoc analysis among female participants who had gone through the menopause showed no significant dierences between efimosfermin and placebo in the least-squares mean change in β-CTX values from baseline to week 24 (data not shown). Overall, treatment-emergent anti-drug antibodies were detected in one (2%) of 41 evaluable participants treated with efimosfermin 300 mg. The presence of anti-drug antibodies did not aect pharmacokinetics, pharmacodynamics, or safety in this individual. At 24 weeks, a significantly higher proportion of participants in the efimosfermin 300 mg Q4W group (14 [45%, 95% CI 27·3–64·0] of 31) achieved improvement in fibrosis without worsening of MASH versus placebo (seven [21%, 8·7–37·9] of 34; p=0·038; figure 2A). The proportion of participants who met the criteria for resolution of MASH without worsening of fibrosis was significantly higher in the efimosfermin 300 mg group (21 [68%, 48·6–83·3] of 31) than in the placebo group (ten [29%, 15·1–47·5] of 34; p=0·002; figure 2B). The proportions of participants who achieved the composite endpoint of at least a one-stage improvement in fibrosis p=0·002 68% p=0·038 p=0·066 45% 60 39% 29% 40 21% 18% 0 Placebo Efimosfermin 300 mg (n=31) (n=34) )%( stnapicitrap fo noitroporP Placebo Efimosfermin Total (n=40) 300 mg Q4W (N=83) (n=43) Any adverse event 22 (55%) 29 (68%) 51 (61%) Any serious adverse event 0 2 (5%)* 2 (2%) Any adverse event leading 0 2 (5%)† 2 (2%) to discontinuation of efimosfermin 300 mg or placebo Any adverse event by severity Grade 1 mild 15 (38%) 24 (56%) 39 (47%) Grade 2 moderate 14 (35%) 18 (42%) 32 (39%) Grade 3 severe 0 2 (5%) 2 (2%) Grade 4 life-threatening 0 0 0 consequences Grade 5 death related to 0 0 0 adverse event Any adverse event leading 0 0 0 to death Most frequent (≥10%) treatment-emergent adverse events Nausea 5 (13%) 14 (33%) 19 (23%) Diarrhoea 3 (8%) 10 (23%) 13 (16%) Vomiting 1 (3%) 7 (16%) 8 (10%) Data are n (%). Participants were only counted once per system organ class and preferred term. FAS=full analysis set. Q4W=every 4 weeks. *One participant with biliary colic (grade 3) and one participant with gastritis (grade 3, considered to be non-drug related by the investigator). †One participant with abdominal pain, nausea, and vomiting and one participant with dehydration. Table 2: Adverse events (FAS population) A Fibrosis improvement of ≥1 stage without B MASH resolution without worsening of C Fibrosis improvement and MASH resolution worsening of MASH at week 24 fibrosis at week 24 at week 24 Placebo Efimosfermin 300 mg Placebo Efimosfermin 300 mg (n=31) (n=34) (n=31) (n=34) Figure 2: Proportion of participants reaching histology endpoints at week 24 (BAS population) (A) Proportion of participants with improvement in liver fibrosis by at least one stage and no worsening of steatohepatitis (defined as no increase in NAS for ballooning, inflammation, or steatosis) at week 24. (B) Proportion of participants with MASH resolution (defined as NAS of 0 for ballooning and 0–1 for inflammation) without worsening of fibrosis at week 24. (C) Proportion of participants who achieved fibrosis improvement and MASH resolution at week 24. p values comparing efimosfermin 300 mg response rates to placebo response rates were estimated by Cochran–Mantel–Haenszel tests stratified by baseline fibrosis stage. Error bars indicate 95% CIs. BAS=biopsy analysis set. MASH=metabolic dysfunction-associated steatohepatitis. NAS=Nonalcoholic Fatty Liver Disease Activity Score. Articles and MASH resolution were 12 (39%, 21·8–57·8) of 31 for figure 2C). A higher proportion of patients in the ITT the efimosfermin 300 mg group and efimosfermin efimosfermin 300 mg group reached these endpoints six (18%, 6·8–34·5) of 34 for the placebo group (p=0·066; compared with the placebo group (appendix p 17). Improvement in fibrosis without worsening of MASH Placebo Efimosfermin and resolution of MASH without worsening of fibrosis 300 mg Q4W Liver fat and fibrosis biomarkers HFF percentage*† Placebo Efimosfermin 300 mg Q4W Number of patients 31 34 Absolute least-squares −2·8 (1·1) −10·8 (1·0) (Continued from previous column) mean change from baseline Relative least-squares mean −9·3 (4·8) −16·4 (4·5) (SE) at week 28, change from baseline (SE) percentage points at week 28, kPA 95% CI −4·9 to −0·6 −12·9 to −8·8 95% CI −18·9 to 0·3 −25·5 to −7·3 Least-squares mean −8·1 ·· Least-squares mean −7·1 ·· treatment difference (−11·0 to −5·1) treatment difference (−20·4 to 6·2) (95% CI), percentage (95% CI), kPA points p value 0·29 ·· p value <0·001 ·· ELF score†‡ Relative least-squares mean −15·6 (4·9) −49·4 (4·7) Number of patients 31 32 change from baseline (SE) at week 28, percentage Absolute least-squares −0·2 (0·1) −0·7 (0·1) points mean change from baseline (SE) at week 24 95% CI −25·3 to −5·8 −58·7 to −40·1 95% CI −0·5 to 0·0 −0·9 to −0·5 Least-squares mean −33·8 ·· treatment difference (−47·4 to −20·2) Least-squares mean −0·5 ·· (95% CI), percentage treatment difference (−0·8 to −0·2) points (95% CI) p value <0·001 ·· p value 0·005 ·· Pro-C3 percentage†‡§ Cardiometabolic biomarkers Number of patients 33 31 Adiponectin†‡, µg/L Absolute least-squares −10·6 (2·2) −24·4 (2·3) Number of patients 33 31 mean change from baseline Absolute least-squares 13·7 (409·6) 2988·6 (422·6) (SE) at week 24, percentage mean change from baseline points (SE) at week 24, µg/L 95% CI −15·0 to −6·2 −28·9 to −19·8 95% CI −805·3 to 832·7 2143·6 to Least-squares mean −13·8 ·· 3833·6 treatment difference (−20·2 to −7·3) Least-squares mean 2975·0 ·· (95% CI), percentage treatment difference (1798·1 to 4151·8) points (95% CI), µg/L p value <0·001 ·· p value <0·001 ·· Relative least-squares mean −16·6 (4·2) −44·6 (4·4) Relative least-squares mean −0·9 (6·1) 68·3 (6·3) change from baseline (SE) change from baseline (SE) at week 24, percentage at week 24, µg/L points 95% CI −13·1 to 11·2 55·8 to 80·9 95% CI −25·1 to −8·1 −53·4 to −35·9 Least-squares mean 69·3 ·· Least-squares mean −28·0 ·· treatment difference (51·8 to 86·7) treatment difference (−40·3 to −15·7) (95% CI), µg/L (95% CI), percentage p value <0·001 ·· points HbA percentage†‡ p value <0·001 ·· 1c Number of patients 33 31 VCTE LSM†‡, kPA Absolute least-squares 0·0 (0·1) −0·4 (0·1) Number of patients 33 37 mean change from baseline Absolute least-squares −1·5 (0·6) −1·9 (0·6) (SE) at week 24, percentage mean change from baseline points (SE) at week 28, kPA 95% CI −0·2 to 0·3 −0·6 to −0·1 95% CI −2·7 to −0·3 −3·0 to −0·7 Least-squares mean −0·4 ·· Least-squares mean −0·4 ·· treatment difference (−0·8 to 0·0) treatment difference (−2·1 to 1·3) (95% CI), (95% CI), kPA percentage points p value 0·64 ·· p value 0·041 ·· (Table 3 continues in next column) (Table 3 continues in next column) 800 Articles Placebo Efimosfermin Placebo Efimosfermin 300 mg Q4W 300 mg Q4W (Continued from previous column) (Continued from previous column) Triglycerides†‡, mmol/L Total cholesterol†‡, mmol/L Number of patients 33 31 Number of patients 32 31 Absolute least-squares 0·0 (0·1) −0·5 (0·1) Absolute least-squares −0·1 (0·1) −0·2 (0·1) mean change from baseline mean change from baseline (SE) at week 24, mmol/L (SE) at week 24, mmol/L 95% CI −0·3 to 0·2 −0·7 to −0·2 95% CI −0·4 to 0·2 −0·4 to 0·1 Least-squares mean −0·4 ·· Least-squares mean 0·0 ·· treatment difference (−0·8 to 0·0) treatment difference (−0·4 to 0·3) (95% CI), mmol/L (95% CI), mmol/L p value 0·030 ·· p value 0·85 ·· Relative least-squares mean 5·2 (6·8) −20·6 (7·0) Relative least-squares mean −0·7 (2·7) −1·6 (2·7) change from baseline (SE) at change from baseline (SE) week 24, mmol/L at week 24, mmol/L 95% CI −8·4 to 18·8 −34·6 to −6·6 95% CI −6·0 to 4·7 −7·0 to 3·8 Least-squares mean −25·8 ·· Least-squares mean −1·0 ·· treatment difference (−45·6 to −6·1) treatment difference (−8·7 to 6·7) (95% CI), mmol/L (95% CI), mmol/L p value 0·011 ·· p value 0·80 ·· HDL cholesterol†‡, mmol/L Bodyweight, kg Number of patients 32 31 Number of patients 40 43 Absolute least-squares 0·0 (0·0) 0·2 (0·0) Absolute least-squares −1·0 (0·1) −1·5 (0·9) mean change from baseline mean change from baseline (SE) at week 24, mmol/L (SE) at week 24, kg 95% CI −0·1 to 0·0 0·1 to 0·2 95% CI −2·7 to 0·7 −3·2 to 0·2 Least-squares mean 0·2 ·· Least-squares mean −0·5 ·· treatment difference (0·1 to 0·3) treatment difference (−2·9 to 2·0) (95% CI), mmol/L (95% CI), kg p value <0·001 p value 0·70 ·· Relative least-squares mean −2·6 (2·5) 16·4 (2·5) Relative least-squares mean −1·1 (0·8) −1·5 (0·8) change from baseline (SE) at change from baseline (SE) week 24, mmol/L at week 24, kg 95% CI −7·6 to 2·3 11·4 to 21·4 95% CI −2·8 to 0·5 −3·1 to 0·1 Least-squares mean 19·1 ·· Least-squares mean −0·4 ·· treatment difference (12·1 to 26·1) treatment difference (−2·7 to 1·9) (95% CI), mmol/L (95% CI), kg p value <0·001 ·· p value 0·75 ·· LDL cholesterol†‡, mmol/L The p values reflect the comparison of the least-squares mean change (or percent Number of patients 30 31 change) between placebo and efimosfermin groups. ALT=alanine Absolute least-squares −0·1 (0·1) −0·1 (0·1) aminotransferase. AST=aspartate aminotransferase. ELF=Enhanced Liver Fibrosis. mean change from baseline FAS=full analysis set. HbA 1c =glycated haemoglobin. HFF=hepatic fat fraction. (SE) at week 24, mmol/L mFAS=modified full analysis set. Pro-C3=N-terminal propeptide of type 3 collagen. Q4W=every 4 weeks. VCTE LSM=vibration-controlled transient 95% CI −0·3 to 0·2 −0·3 to 0·1 elastography liver stiffness measurement. *Data reported from participants in the Least-squares mean −0·1 ·· mFAS population (ie, participants in FAS with valid baseline and week 28 HFF treatment difference (−0·4 to 0·3) results). †Least-squares mean, SE, 95% CI, and p values were based on ANCOVA (95% CI), mmol/L models with change or percentage change from baseline as the dependent p value 0·76 ·· variable, and baseline and treatment as covariates. ‡Data reported from participants in the FAS population. §Pro-C3 values are based on the Roche Relative least-squares mean 3·5 (4·6) −0·5 (4·5) Cobas e801 (Nordic BioScience) assay. change from baseline (SE) at week 24, mmol/L Table 3: Change from baseline at week 24 or week 28 in key liver and 95% CI −5·7 to 12·6 −9·5 to 8·4 cardiometabolic biomarkers (mFAS and FAS populations) Least-squares mean −4·0 ·· treatment difference (−16·9 to 8·9) (95% CI), mmol/L by demographic and clinical subgroups of patients are p value 0·54 ·· presented in the appendix (p 2), but given that these (Table 3 continues in next column) analyses were not prespecified, they are for descriptive purposes only. A significantly higher proportion of participants in the efimosfermin 300 mg Q4W group reached both MASH Articles p<0·001 79% 80 p<0·001 50% p=0·003 23% 40 32% 6% 20 3% Placebo Efimosfermin 300 mg (n=31) (n=34) Figure 3: Proportion of participants achieving HFF reduction thresholds and liver fat normalisation at week 28 (mFAS population) (A) Proportion of participants who reached at least a 30% relative HFF reduction at week 28. (B) Proportion of participants who reached at least a 50% relative HFF reduction at week 28. (C) Proportion of participants who reached liver fat normalisation (≤5%) at week 28. p values comparing efimosfermin 300 mg response rates with placebo response rates were estimated by Cochran-Mantel-Haenszel tests stratified by baseline fibrosis stage. Errors bars indicate 95% CIs, which were estimated using the binomial exact method. HFF=hepatic fat fraction. mFAS=modified full analysis set. resolution with at least a 2-point improvement in NAS Significant changes in HbA were seen as early as 1c without worsening of fibrosis and an improvement in 12 weeks in the efimosfermin 300 mg treatment group NAS of at least 2 points at 24 weeks, versus placebo (appendix p 7). In a post-hoc analysis of participants (appendix p 4). with type 2 diabetes (efimosfermin 300 mg, n=20; Significant absolute and relative reductions in HFF placebo, n=15), absolute least-squares mean change measured by MRI-PDFF were observed in the from baseline at week 24 in HbA was significantly 1c efimosfermin 300 mg Q4W group versus the placebo reduced with efimosfermin 300 mg versus placebo group at week 28 (table 3). A significantly greater (p=0·034). Absolute and relative least-squares mean proportion of participants in the efimosfermin 300 mg changes from baseline at week 24 in triglycerides and group (17 [50%, 95% CI 32·4–67·6] of 34) reached at HDL cholesterol concentrations were significantly least 50% relative HFF reduction at week 28 versus improved in the efimosfermin 300 mg group versus the placebo (two [6%, 0·8–21·4] of 31; p<0·001; figure 3). A placebo group (table 3). significantly greater proportion of participants in the efimosfermin 300 mg group (11 [32%, 17·4–50·5] of 34) Discussion reached liver fat normalisation (≤5%) at week 28 versus This phase 2 trial evaluating the safety and ecacy of placebo (one [3%, 0·1–16·7] of 31; p=0·003; figure 3). efimosfermin, an FGF21 analogue taken once per month, Significant reductions in ELF absolute change from demonstrated significant improvements in both key baseline and Pro-C3 relative change from baseline were regulatory endpoints, including at least a one-stage fibrosis observed as early as week 4 and sustained over 24 weeks improvement with no worsening of MASH and MASH in the efimosfermin 300 mg Q4W group compared with resolution with no worsening of fibrosis at 24 weeks in the placebo group (table 3; appendix p 11). VCTE least- participants with F2–F3 fibrosis due to MASH, with squares means at week 28 were not significantly dierent improvements observed after six doses. These endpoints in the efimosfermin 300 mg group versus placebo serve as crucial surrogates for clinical outcomes in MASH, (table 3). Rapid and significant improvements from as fibrosis is a primary predictor of long-term clinical baseline to week 24 in liver injury biomarkers (ALT and outcomes and is a central treatment goal of MASH.12,20 AST) were observed in the efimosfermin 300 mg group MASH resolution is linked to improved fibrosis, which versus placebo (appendix p 6). reflects histological improvements in liver inflammation Relative least-squares mean change from baseline at and hepatocyte injury, factors that are key drivers of fibrosis week 24 in adiponectin concentrations was significantly progression.20–22 As has been reported in placebo groups in improved in the efimosfermin 300 mg Q4W group previous MASH trials,23,24 improvements in histological versus the placebo group (p<0·001; table 3). Absolute response were seen in the placebo cohort in this trial. The least-squares mean change from baseline at week 24 in proportion of patients in the placebo cohort who had some HbA was significantly lower with efimosfermin measure of response was relatively high for both MASH 1c 300 mg treatment versus placebo (p=0·041; table 3). resolution without worsening of fibrosis and NAS 802 )%( stnapicitrap fo noitroporP A ≥30% relative HFF reduction at week 28 B ≥50% relative HFF reduction at week 28 C Liver fat normalisation (≤5%) at week 28 Placebo Efimosfermin 300 mg Placebo Efimosfermin 300 mg (n=31) (n=34) (n=31) (n=34) Articles improvement, which might be caused by the Hawthorne than placebo in achieving fibrosis improvement without eect, factors such as lifestyle modifications, or natural worsening of MASH and MASH resolution without disease variability.23,24 Non-invasive markers of liver health worsening fibrosis in participants with biopsy-confirmed not only corroborate histological findings but also oer a F2–F3 fibrosis due to MASH after 24 weeks. Beyond dynamic assessment of treatment response. In this study, these key regulatory endpoints, efimosfermin provided improvements in non-invasive markers of fibrosis (ELF additional benefit in improving non-invasive markers of and Pro-C3) and liver injury (ALT and AST) were evident hepatic and cardiometabolic health and was generally as early as 4 weeks after treatment initiation. Reductions in well tolerated. These promising results support the liver stiness with efimosfermin as assessed by VCTE potential for efimosfermin as a once-per-month were not significantly dierent from placebo at week 24. treatment for MASH, warranting further investigation in This finding might reflect measurement variability of larger, longer, phase 3 clinical trials. VCTE. A substantial proportion of participants also Contributors reached meaningful improvements in HFF. These TO designed the study. MJK and TO provided medical oversight. MJK, JZ, findings, combined with histological data, reinforce the and TO performed statistical analysis. MJK, GB, JZ, and TO interpreted potential of efimosfermin with once-per-month dosing as the data. MJK, GB, TO, BJ, MN, KVK, and RL provided critical review and editing of the manuscript. All authors had access to the study data, treatment for MASH. The extrahepatic eects of verified the data, and were responsible for the decision to submit the efimosfermin are noteworthy, given the high rates of manuscript for publication. metabolic comorbidities seen in MASH. In the current Declaration of interests study, after only six doses, efimosfermin led to MN has served as a consultant to Altimmune, Alligos, AstraZeneca, improvements in metabolic biomarkers, including HbA , Boehringer Ingelheim, Boston Pharma, Cytodyn, GSK, Lilly, Madrigal, 1c Merck, Novo Nordisk, Terns, and Takeda, has served as Principal adiponectin, triglycerides, and HDL cholesterol. Investigator for a drug study for Allergan, Akero, Boehringer Ingelheim, Additionally, the significant reduction in HbA 1c among BMS, Gilead, Galectin, Genfit, GSK, Conatus, Corcept, Enanta, Madrigal, participants with diabetes was clinically meaningful.25,26 Novartis, Novo Nordisk, Shire, Takeda, Terns, Viking, and Zydus, holds Consistent with previous studies,14 efimosfermin was stock in Rivus Pharma, Cytodyn, and ChronWell, and serves as speaker for Madrigal. KK serves as a consultant to Arbormed, Boehringer generally well tolerated with a low rate of discontinuation Ingelheim, CymaBay, Genfit, Gilead, GSK, HighTide, Inipharm, due to adverse events. The overall rate of adverse events Intercept, Ipsen, Madrigal, Mirum, NGM, Novo Nordisk, Orphalan, compares favourably with other drugs in this class, Pfizer, 89bio, and Zydus, has received research support paid to his supporting the safety profile of efimosfermin.12,13 There institution from Akero, AstraZeneca, Boston Pharmaceuticals, Boehringer Ingelheim, Corcept, Gilead, GSK, Hanmi, Intercept, Inventiva, Janssen, were no safety signals in bone biomarkers or fractures Madrigal, Mirum, Novo Nordisk, NGM, Pfizer, Pliant, Terns, Viking, seen over the 24-week study period. Although this finding 89bio, and Zydus, has served as a speaker for AbbVie, Gilead, Intercept, is important because FGF21 might aect bone turnover,8 and Ipsen, has received royalties or licenses from UpToDate, has received changes in bone mineral density via dual-energy x-ray payment from the Department of Justice for expert testimony, has served on a data safety monitoring or advisory board for Medpace and MSD, and absorptiometry scans or bone architecture by imaging has received stock or stock options from Inipharm. JZ, BJ, and MJK are was not assessed in this study. These changes might also employees of Boston Pharmaceuticals working on behalf of GSK as of not be evident in a 24-week study, and longer studies July 7, 2025. TO and GB were employees of Boston Pharmaceuticals at the might be needed to fully assess these eects. time this work was conducted. RL serves as a consultant to 89bio, Aardvark Therapeutics, Altimmune, Arrowhead Pharmaceuticals, A limitation of this study is the moderate sample size, AstraZeneca, Boston Pharmaceuticals, Cascade Pharmaceuticals, Eli Lilly, which might reduce the generalisability of the findings Gilead, Glympse Bio, Inipharm, Intercept, Inventiva, Ionis, Janssen, and limit the statistical power to detect significant Lipidio, Madrigal, Merck, NeuroBo, Novo Nordisk, Pfizer, Sagimet, dierences. Participants enrolled in this study had a BMI Takeda, Terns Pharmaceuticals, and Viking Therapeutics, reports research grants paid to his institution from Arrowhead Pharmaceuticals, of at least 27 kg/m² and at least two components of AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, metabolic syndrome. Although these inclusion criteria Galectin Therapeutics, Gilead, Hanmi, Intercept, Inventiva, Ionis, are typical for MASH trials, they represent a population Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic with an elevated metabolic risk profile. Additionally, the Incytes, and Terns Pharmaceuticals, has stock options in Sagimet Biosciences, is the co-founder of LipoNexus, and has received funding 24-week treatment duration is relatively short as fibrosis from NIDDK (P30DK120515), NHLBI (P01HL147835), and the can take years to regress depending on severity. Although John C Martin Foundation (RP124). a significantly higher proportion of participants reached Data sharing fibrosis improvement of at least one stage without The datasets generated and analysed during the current study are MASH worsening and MASH resolution without commercially sensitive and are not publicly available. Requests for data worsening of fibrosis after 24 weeks, histological supporting findings in the manuscript should be made to the corresponding author and will be reviewed individually. Individual response rates and non-invasive markers might show patient-level raw data containing confidential or identifiable patient improved therapeutic benefit with longer treatment. An information are subject to patient privacy and cannot be shared. Data extension study is ongoing in an unblinded manner for can be shared in the form of aggregated summaries. an additional 24 weeks to further assess safety and Acknowledgments ecacy up to 48 weeks of treatment. This study was sponsored by Boston Pharmaceuticals. On July 7, 2025, GSK acquired Boston Pharmaceuticals’ lead asset, efimosfermin alfa. The results of this phase 2 trial showed that treatment Medical writing and editorial assistance were provided by Lindsay Achzet, with efimosfermin once per month was more ecacious Liz McSpiritt, and Callie Grimes, of Peloton Advantage, an OPEN Health Articles company, and were funded by Boston Pharmaceuticals and GSK. 14 Loomba R, Kowdley KV, Rodriguez J, et al. Efimosfermin alfa Cindy Xu and Matthew Bryant provided input into the analysis of the (BOS-580), a long-acting FGF21 analogue, in participants with study and writing. We thank all the participants as well as site sta and phenotypic metabolic dysfunction–associated steatohepatitis: investigators. a phase 2a randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol 2025; 10: 734–45. References 15 Stine JG, Munaganuru N, Barnard A, et al. Change in MRI-PDFF 1 Rinella ME, Lazarus JV, Ratziu V, et al. 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Lancet Gastroenterol Hepatol 2023; 8: 1080–93. 804 --- [PDF原文](https://sci-net.xyz/storage/7932541/b5b1ad7db4aef25d7888ecab145adadd305ddfb799eaa8374fda22f4fc767320/Efimosfermin-alfa-BOS-580-once-per-month-in-people-with-metabolic-dysfunction-associated.pdf) DOI: 10.1016/S0140-6736(25)02276-7