Trial Outcomes & Findings for A Study of Efruxifermin in Non-Cirrhotic Subjects With Histologically Confirmed Nonalcoholic Steatohepatitis (NASH) (NCT NCT04767529)

NCT ID: NCT04767529

Last Updated: 2025-06-18

Results Overview

Proportions of subjects in EFX vs placebo groups with improvement in liver fibrosis, defined as ≥ 1 stage NASH Clinical Research Network \[CRN\] fibrosis score (score ranges from 0 to 4, increasing with fibrosis severity), and no worsening of steatohepatitis (no increase in NASH Activity Score \[NAS\], which ranges from 0 to 8 and is the sum of scores of steatosis, lobular inflammation, and hepatocyte ballooning), at Week 24

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 128 participants
• Primary outcome timeframe: 24 Weeks
• Results posted on: 2025-06-18

Participant Flow

Participant milestones

Measure	Placebo double-blind, once-weekly subcutaneous administration	Efruxifermin 28 mg double-blind, once-weekly subcutaneous administration	Efruxifermin 50 mg double-blind, once-weekly subcutaneous administration
Overall Study STARTED	43	42	43
Overall Study Started Study Drug	43	40	43
Overall Study Completed Week 96 Treatment	34	26	27
Overall Study Discontinued Treatment	9	16	16
Overall Study Completed Week 24 Visit	42	37	36
Overall Study COMPLETED	34	27	27
Overall Study NOT COMPLETED	9	15	16

Reasons for withdrawal

Measure	Placebo double-blind, once-weekly subcutaneous administration	Efruxifermin 28 mg double-blind, once-weekly subcutaneous administration	Efruxifermin 50 mg double-blind, once-weekly subcutaneous administration
Overall Study Adverse Event	0	4	3
Overall Study clinical outcomes endpoint (excluding death)	1	3	3
Overall Study Required use of a prohibited medication	0	1	0
Overall Study Withdrawal by Subject	7	5	4
Overall Study At the discretion of the Investigator or Sponsor for noncompliance	1	0	3
Overall Study Lost to Follow-up	0	2	3

Baseline Characteristics

Baseline weight not available for 2 participants

Baseline characteristics by cohort

Measure	Placebo n=43 Participants Double-blind, once-weekly subcutaneous administration	Efruxifermin 28 mg n=42 Participants Double-blind, once-weekly subcutaneous administration	Efruxifermin 50 mg n=43 Participants Double-blind, once-weekly subcutaneous administration	Total n=128 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=43 Participants	0 Participants n=42 Participants	0 Participants n=43 Participants	0 Participants n=128 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=43 Participants	31 Participants n=42 Participants	37 Participants n=43 Participants	102 Participants n=128 Participants
Age, Categorical >=65 years	9 Participants n=43 Participants	11 Participants n=42 Participants	6 Participants n=43 Participants	26 Participants n=128 Participants
Age, Continuous	55.0 years STANDARD_DEVIATION 10.1 • n=43 Participants	56.5 years STANDARD_DEVIATION 9.3 • n=42 Participants	52.4 years STANDARD_DEVIATION 11.4 • n=43 Participants	54.7 years STANDARD_DEVIATION 10.4 • n=128 Participants
Sex: Female, Male Female	27 Participants n=43 Participants	29 Participants n=42 Participants	23 Participants n=43 Participants	79 Participants n=128 Participants
Sex: Female, Male Male	16 Participants n=43 Participants	13 Participants n=42 Participants	20 Participants n=43 Participants	49 Participants n=128 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=43 Participants	17 Participants n=42 Participants	20 Participants n=43 Participants	52 Participants n=128 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=43 Participants	25 Participants n=42 Participants	23 Participants n=43 Participants	76 Participants n=128 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=43 Participants	0 Participants n=42 Participants	0 Participants n=43 Participants	0 Participants n=128 Participants
Race/Ethnicity, Customized Race · White	39 Participants n=43 Participants	38 Participants n=42 Participants	41 Participants n=43 Participants	118 Participants n=128 Participants
Race/Ethnicity, Customized Race · Black or African American	2 Participants n=43 Participants	1 Participants n=42 Participants	1 Participants n=43 Participants	4 Participants n=128 Participants
Race/Ethnicity, Customized Race · Asian	2 Participants n=43 Participants	3 Participants n=42 Participants	0 Participants n=43 Participants	5 Participants n=128 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=43 Participants	0 Participants n=42 Participants	0 Participants n=43 Participants	0 Participants n=128 Participants
Race/Ethnicity, Customized Race · American Indian or Alaskan Native	0 Participants n=43 Participants	0 Participants n=42 Participants	0 Participants n=43 Participants	0 Participants n=128 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=43 Participants	0 Participants n=42 Participants	1 Participants n=43 Participants	1 Participants n=128 Participants
Region of Enrollment United States	43 participants n=43 Participants	42 participants n=42 Participants	43 participants n=43 Participants	128 participants n=128 Participants
Baseline Fibrosis Stage Fibrosis stage 2	13 Participants n=43 Participants	15 Participants n=42 Participants	16 Participants n=43 Participants	44 Participants n=128 Participants
Baseline Fibrosis Stage Fibrosis stage 3	30 Participants n=43 Participants	27 Participants n=42 Participants	27 Participants n=43 Participants	84 Participants n=128 Participants
Weight	107.6 kg STANDARD_DEVIATION 25.6 • n=43 Participants • Baseline weight not available for 2 participants	103.9 kg STANDARD_DEVIATION 22.7 • n=40 Participants • Baseline weight not available for 2 participants	102.8 kg STANDARD_DEVIATION 21.1 • n=43 Participants • Baseline weight not available for 2 participants	104.8 kg STANDARD_DEVIATION 23.2 • n=126 Participants • Baseline weight not available for 2 participants
Type 2 diabetes status T2D yes	28 Participants n=43 Participants	32 Participants n=42 Participants	30 Participants n=43 Participants	90 Participants n=128 Participants
Type 2 diabetes status T2D no	15 Participants n=43 Participants	10 Participants n=42 Participants	13 Participants n=43 Participants	38 Participants n=128 Participants

PRIMARY outcome

Timeframe: 24 Weeks

Population: Week 24 Liver Biopsy Analysis Set

Proportions of subjects in EFX vs placebo groups with improvement in liver fibrosis, defined as ≥ 1 stage NASH Clinical Research Network [CRN] fibrosis score (score ranges from 0 to 4, increasing with fibrosis severity), and no worsening of steatohepatitis (no increase in NASH Activity Score [NAS], which ranges from 0 to 8 and is the sum of scores of steatosis, lobular inflammation, and hepatocyte ballooning), at Week 24

Outcome measures

Measure	Placebo n=41 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=38 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=34 Participants double-blind, once-weekly subcutaneous injection
Effect of Efruxifermin (EFX) vs Placebo on Fibrosis Regression in Participants With Metabolic Dysfunction-associated Steatohepatitis (MASH)-Associated Stage 2 or 3 Fibrosis (F2 or F3)	8 Participants	15 Participants	14 Participants

SECONDARY outcome

Timeframe: 96 Weeks

Population: Week 96 Liver Biopsy Analysis Set

Proportions of subjects in EFX vs baseline groups who achieve improvement in liver fibrosis (decrease of ≥ 1 stage in NASH CRN fibrosis score) and no worsening of steatohepatitis (no increase in NAS for ballooning, inflammation, or steatosis) at Week 96

Outcome measures

Measure	Placebo n=34 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=26 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=28 Participants double-blind, once-weekly subcutaneous injection
Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage and no Worsening of Steatohepatitis at Week 96	8 Participants	12 Participants	21 Participants

SECONDARY outcome

Timeframe: 24 and 96 weeks

Population: Liver Biopsy Analysis Set - Week 24 and Week 96

Proportions of subjects in EFX vs placebo groups who achieve resolution of steatohepatitis (defined as a NAS of 0-1 for inflammation, 0 for ballooning, and any value for steatosis) and no worsening of liver fibrosis (determined by the NASH CRN criteria)

Outcome measures

Measure	Placebo n=41 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=38 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=34 Participants double-blind, once-weekly subcutaneous injection
Proportion of Subjects Who Achieve Resolution of Steatohepatitis and no Worsening of Liver Fibrosis at Week 24 and Week 96 Week 24	6 Participants	18 Participants	26 Participants
Proportion of Subjects Who Achieve Resolution of Steatohepatitis and no Worsening of Liver Fibrosis at Week 24 and Week 96 Week 96	8 Participants	16 Participants	16 Participants

SECONDARY outcome

Timeframe: 24 and 96 Weeks

Population: Week 24 and Week 96 Liver Biopsy Analysis Sets

Proportion of subjects in EFX vs placebo groups who achieve improvement in liver fibrosis (decrease ≥ 1 stage in NASH CRN fibrosis score)

Outcome measures

Measure	Placebo n=41 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=38 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=34 Participants double-blind, once-weekly subcutaneous injection
Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage at Week 24 and Week 96 Week 24	9 Participants	15 Participants	14 Participants
Proportion of Subjects Who Achieve Improvement in Liver Fibrosis ≥ 1 Stage at Week 24 and Week 96 Week 96	9 Participants	12 Participants	21 Participants

SECONDARY outcome

Timeframe: 24 and 96 Weeks

Population: Week 24 and 96 MRI-PDFF Analysis Set

Change from baseline in hepatic fat fraction, measured by magnetic resonance imaging proton-density fat fraction (MRI-PDFF):

Week 24 and Week 96 MRI-PDFF Analysis Set

Outcome measures

Measure	Placebo n=42 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=38 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=35 Participants double-blind, once-weekly subcutaneous injection
Change From Baseline in Hepatic Fat Fraction in EFX vs Placebo Groups Week 24	-1.9 percentage hepatic fat Standard Error 0.78	-8.8 percentage hepatic fat Standard Error 0.84	-11.2 percentage hepatic fat Standard Error 0.86
Change From Baseline in Hepatic Fat Fraction in EFX vs Placebo Groups Week 96	-2.5 percentage hepatic fat Standard Error 0.89	-6.3 percentage hepatic fat Standard Error 1.01	-8.3 percentage hepatic fat Standard Error 1.00

SECONDARY outcome

Timeframe: 24 and 96 weeks

Population: Full Analysis Set

Change from baseline of lipoproteins (triglycerides, Non-HDL-C, HDL-C and LDL-C) in EFX vs placebo groups

Outcome measures

Measure	Placebo n=43 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=42 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=43 Participants double-blind, once-weekly subcutaneous injection
Change From Baseline in Lipoproteins at Week 24 and Week 96 Change from baseline in HDL cholesterol (mg/dL) at Week 96	1.3 mg/dL Standard Error 1.43	7.3 mg/dL Standard Error 1.59	10.7 mg/dL Standard Error 1.57
Change From Baseline in Lipoproteins at Week 24 and Week 96 Change from baseline in LDL cholesterol (mg/dL) at Week 96	-1.3 mg/dL Standard Error 4.74	-1.2 mg/dL Standard Error 5.29	-1.4 mg/dL Standard Error 5.23
Change From Baseline in Lipoproteins at Week 24 and Week 96 Change from baseline in non-HDL cholesterol (mg/dL) at Week 96	1.5 mg/dL Standard Error 5.31	-4.5 mg/dL Standard Error 5.92	-6.7 mg/dL Standard Error 5.86
Change From Baseline in Lipoproteins at Week 24 and Week 96 Change from baseline in triglycerides (mg/dL) at Week 24	10.5 mg/dL Standard Error 6.82	-41.1 mg/dL Standard Error 7.26	-44.7 mg/dL Standard Error 7.20
Change From Baseline in Lipoproteins at Week 24 and Week 96 Change from baseline in triglycerides (mg/dL) at Week 96	16.1 mg/dL Standard Error 7.69	-26.9 mg/dL Standard Error 8.63	-31.7 mg/dL Standard Error 8.54
Change From Baseline in Lipoproteins at Week 24 and Week 96 Change from baseline in HDL cholesterol (mg/dL) at Week 24	-0.9 mg/dL Standard Error 1.09	10.1 mg/dL Standard Error 1.16	11.5 mg/dL Standard Error 1.15
Change From Baseline in Lipoproteins at Week 24 and Week 96 Change from baseline in LDL cholesterol (mg/dL) at Week 24	4.0 mg/dL Standard Error 3.47	-10.4 mg/dL Standard Error 3.7	-9.6 mg/dL Standard Error 3.69
Change From Baseline in Lipoproteins at Week 24 and Week 96 Change from baseline in non-HDL cholesterol (mg/dL) at Week 24	6.1 mg/dL Standard Error 3.83	-16.6 mg/dL Standard Error 4.08	-16.6 mg/dL Standard Error 4.05

SECONDARY outcome

Timeframe: 24 Weeks, 96 Weeks

Population: Biomarker Analysis Set

Change from baseline in hemoglobin A1c (glycated hemoglobin, HbA1c) in EFX vs placebo groups

Outcome measures

Measure	Placebo n=43 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=40 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=43 Participants double-blind, once-weekly subcutaneous injection
Change From Baseline of Hemoglobin A1c (Glycated Hemoglobin, HbA1c) at Week 24 and Week 96 Change from baseline in hemoglobin A1C (HbA1c, %) at Week 96	-0.0 % glycated hemoglobin Standard Error 0.22	0.0 % glycated hemoglobin Standard Error 0.24	0.2 % glycated hemoglobin Standard Error 0.24
Change From Baseline of Hemoglobin A1c (Glycated Hemoglobin, HbA1c) at Week 24 and Week 96 Change from baseline in hemoglobin A1C (HbA1c, %) at Week 24	-0.0 % glycated hemoglobin Standard Error 0.12	-0.3 % glycated hemoglobin Standard Error 0.12	-0.4 % glycated hemoglobin Standard Error 0.12

SECONDARY outcome

Timeframe: 24 Weeks, 96 Weeks

Population: Biomarker Analysis Set

Change from baseline in C-peptide in EFX vs placebo groups

Outcome measures

Measure	Placebo n=43 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=40 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=43 Participants double-blind, once-weekly subcutaneous injection
Change From Baseline in C-peptide at Week 24 and Week 96 Change from baseline in C-Peptide at Week 24	0.0 ng/mL Standard Error 0.19	-0.8 ng/mL Standard Error 0.20	-1.2 ng/mL Standard Error 0.19
Change From Baseline in C-peptide at Week 24 and Week 96 Change from baseline in C-Peptide at Week 96	-0.2 ng/mL Standard Error 0.22	-0.4 ng/mL Standard Error 0.25	-1.0 ng/mL Standard Error 0.25

SECONDARY outcome

Timeframe: 24 Weeks, 96 Weeks

Population: Biomarker Analysis Set

Change from baseline in adiponectin in EFX vs placebo groups

Outcome measures

Measure	Placebo n=43 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=40 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=43 Participants double-blind, once-weekly subcutaneous injection
Change From Baseline in Adiponectin at Week 24 and Week 96 Change from baseline in adiponectin at Week 96	531.5 ng/mL Standard Error 416.93	975.3 ng/mL Standard Error 459.40	2018.3 ng/mL Standard Error 458.91
Change From Baseline in Adiponectin at Week 24 and Week 96 Change from baseline in adiponectin at Week 24	296.4 ng/mL Standard Error 312.56	1411.5 ng/mL Standard Error 333.48	3088.8 ng/mL Standard Error 333.82

SECONDARY outcome

Timeframe: 24 Weeks, 96 Weeks

Population: Biomarker Analysis Set

Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in EFX vs placebo groups

The Homeostatic Model Assessment of Insulin Resistance, HOMA-IR, is a calculated index that estimates insulin resistance based on fasting glucose and insulin levels. Higher values indicate greater insulin resistance.

< 1.0: Normal insulin sensitivity 1.0-1.9: Mild insulin resistance 2.0-2.9: Moderate insulin resistance > 2.9: Severe insulin resistance

Outcome measures

Measure	Placebo n=43 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=40 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=43 Participants double-blind, once-weekly subcutaneous injection
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 and Week 96 Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24	0.7 units on a scale Standard Error 1.09	-4.7 units on a scale Standard Error 1.19	-5.6 units on a scale Standard Error 1.14
Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 24 and Week 96 Change from baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 96	-1.3 units on a scale Standard Error 0.87	-4.1 units on a scale Standard Error 1.01	-5.5 units on a scale Standard Error 0.99

SECONDARY outcome

Timeframe: 24 and 96 Weeks

Population: Biomarker Analysis Set

Change from Baseline in Enhanced Liver Fibrosis (ELF) Score in EFX vs placebo groups

The Enhanced Liver Fibrosis (ELF) score is a non-invasive blood test that assesses the risk of liver fibrosis and its progression.

Lower risk (<9.8): Suggests a lower risk of advanced liver fibrosis. Mid risk (9.8-11.2): Indicates a moderate risk of disease progression. Higher risk (≥11.3): Suggests a higher risk of developing cirrhosis or liver-related events

Outcome measures

Measure	Placebo n=43 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=40 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=43 Participants double-blind, once-weekly subcutaneous injection
Change From Baseline in Enhanced Liver Fibrosis (ELF) Score at Week 24 and Week 96 Change from baseline in ELF Score at Week 24	0.1 score on a scale Standard Error 0.10	-0.6 score on a scale Standard Error 0.10	-0.7 score on a scale Standard Error 0.10
Change From Baseline in Enhanced Liver Fibrosis (ELF) Score at Week 24 and Week 96 Change from baseline in ELF Score at Week 96	-0.1 score on a scale Standard Error 0.14	-0.7 score on a scale Standard Error 0.16	-0.8 score on a scale Standard Error 0.16

SECONDARY outcome

Timeframe: 24 and 96 Weeks

Population: Biomarker Analysis Set

Change from Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) in EFX vs placebo groups

Outcome measures

Measure	Placebo n=43 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=40 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=43 Participants double-blind, once-weekly subcutaneous injection
Change From Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) at Week 24 and Week 96 Change from baseline in N-terminal Type III Collagen Propeptide (Pro-C3) GEN2 at Week 96	-17.2 ng/mL Standard Error 7.87	-40.2 ng/mL Standard Error 8.89	-50.5 ng/mL Standard Error 8.92
Change From Baseline in N-terminal Type III Collagen Propeptide (Pro-C3) at Week 24 and Week 96 Change from baseline in N-terminal Type III Collagen Propeptide (Pro-C3) GEN2 at Week 24	-2.7 ng/mL Standard Error 6.99	-51.1 ng/mL Standard Error 7.37	-53.9 ng/mL Standard Error 7.37

SECONDARY outcome

Timeframe: 24 and 96 Weeks

Population: Biomarker Analysis Set

Change from Baseline in Collagen III Neo-Peptide (C3M) in EFX vs placebo groups

Outcome measures

Measure	Placebo n=43 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=40 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=43 Participants double-blind, once-weekly subcutaneous injection
Change From Baseline in Collagen III Neo-Peptide (C3M) at Week 24 and Week 96 Change from baseline in Collagen III Neo-Peptide (C3M) (ng/mL) at Week 24	0.2 ng/mL Standard Error 0.35	-0.8 ng/mL Standard Error 0.37	-1.1 ng/mL Standard Error 0.38
Change From Baseline in Collagen III Neo-Peptide (C3M) at Week 24 and Week 96 Change from baseline in Collagen III Neo-Peptide (C3M) (ng/mL) at Week 96	3.1 ng/mL Standard Error 0.71	3.3 ng/mL Standard Error 0.80	4.4 ng/mL Standard Error 0.80

SECONDARY outcome

Timeframe: 24 and 96 Weeks

Population: Biomarker Analysis Set

Change from Baseline in NIS4 score in EFX vs placebo groups

NIS4 scores range from 0 to 1 and are calculated by combining the results of four individual biomarker assays [miR34a-5p, α2-macroglobulin (A2M), YKL-40 and HbA1c] each of which contributes to the test's ability to detect liver inflammation and/or fibrosis.

>0.63: Higher risk of NASH or advanced fibrosis 0.37-0.63: Moderate risk, and additional testing may be considered <0.36: Lower risk of of NASH or advanced fibrosis

Outcome measures

Measure	Placebo n=43 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=40 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=43 Participants double-blind, once-weekly subcutaneous injection
Change From Baseline in NIS4 Score at Week 24 and Week 96 Change from baseline in NIS-4 score at Week 24	-0.0 score on a scale Standard Error 0.03	-0.3 score on a scale Standard Error 0.04	-0.3 score on a scale Standard Error 0.04
Change From Baseline in NIS4 Score at Week 24 and Week 96 Change from baseline in NIS-4 score at Week 96	-0.1 score on a scale Standard Error 0.05	-0.2 score on a scale Standard Error 0.05	-0.3 score on a scale Standard Error 0.05

SECONDARY outcome

Timeframe: 24 and 96 weeks

Population: Full Analysis Set

Change from baseline in body weight (kg) in EFX vs placebo groups

Outcome measures

Measure	Placebo n=43 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=42 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=43 Participants double-blind, once-weekly subcutaneous injection
Change in Body Weight at Week 24 and Week 96 Change from Baseline in Body Weight (kg) at Week 24	-0.6 kg Standard Error 0.82	-0.2 kg Standard Error 0.86	-3.0 kg Standard Error 0.85
Change in Body Weight at Week 24 and Week 96 Change from Baseline in Body Weight (kg) at Week 96	-1.5 kg Standard Error 1.40	-0.3 kg Standard Error 1.53	-3.5 kg Standard Error 1.52

SECONDARY outcome

Timeframe: 24 and 96 weeks

Population: Full Analysis Set

Change from Baseline in Liver Stiffness Evaluated by FibroScan in EFX vs placebo groups at Week 24 and Week 96:

Full Analysis Set

Outcome measures

Measure	Placebo n=43 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=42 Participants double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=43 Participants double-blind, once-weekly subcutaneous injection
Change From Baseline in Liver Stiffness (kPa) at Week 24 and Week 96 Change from baseline in liver stiffness measurement (LSM, kPa) at Week 24	-0.8 kPa Standard Error 0.88	-2.9 kPa Standard Error 0.93	-4.2 kPa Standard Error 0.95
Change From Baseline in Liver Stiffness (kPa) at Week 24 and Week 96 Change from baseline in liver stiffness measurement (LSM, kPa) at Week 96	-0.6 kPa Standard Error 0.98	-4.0 kPa Standard Error 1.09	-7.2 kPa Standard Error 1.08

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 42 other events

Deaths: 0 deaths

Efruxifermin 28 mg

Serious events: 4 serious events

Other events: 38 other events

Deaths: 0 deaths

Efruxifermin 50 mg

Serious events: 7 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=43 participants at risk double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=40 participants at risk double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=43 participants at risk double-blind, once-weekly subcutaneous injection
Gastrointestinal disorders Gastritis	0.00% 0/43 • 96 weeks	2.5% 1/40 • Number of events 1 • 96 weeks	0.00% 0/43 • 96 weeks
Gastrointestinal disorders Esophagitis ulcerative	0.00% 0/43 • 96 weeks	0.00% 0/40 • 96 weeks	2.3% 1/43 • Number of events 1 • 96 weeks
Gastrointestinal disorders Pancreatitis	0.00% 0/43 • 96 weeks	2.5% 1/40 • Number of events 1 • 96 weeks	0.00% 0/43 • 96 weeks
Gastrointestinal disorders Pancreatitis, necrotizing	0.00% 0/43 • 96 weeks	0.00% 0/40 • 96 weeks	2.3% 1/43 • Number of events 1 • 96 weeks
General disorders Non-cardiac chest pain	2.3% 1/43 • Number of events 1 • 96 weeks	0.00% 0/40 • 96 weeks	2.3% 1/43 • Number of events 1 • 96 weeks
General disorders chest pain	0.00% 0/43 • 96 weeks	0.00% 0/40 • 96 weeks	2.3% 1/43 • Number of events 1 • 96 weeks
General disorders Face edema	0.00% 0/43 • 96 weeks	0.00% 0/40 • 96 weeks	2.3% 1/43 • Number of events 1 • 96 weeks
Infections and infestations Appendicitis	2.3% 1/43 • Number of events 1 • 96 weeks	0.00% 0/40 • 96 weeks	0.00% 0/43 • 96 weeks
Infections and infestations COVID-19	0.00% 0/43 • 96 weeks	0.00% 0/40 • 96 weeks	2.3% 1/43 • Number of events 1 • 96 weeks
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/43 • 96 weeks	0.00% 0/40 • 96 weeks	2.3% 1/43 • Number of events 1 • 96 weeks
Respiratory, thoracic and mediastinal disorders Hypoxia	2.3% 1/43 • Number of events 1 • 96 weeks	0.00% 0/40 • 96 weeks	0.00% 0/43 • 96 weeks
Cardiac disorders Arteriospasm coronary	0.00% 0/43 • 96 weeks	2.5% 1/40 • Number of events 1 • 96 weeks	0.00% 0/43 • 96 weeks
Injury, poisoning and procedural complications ankle fracture	0.00% 0/43 • 96 weeks	2.5% 1/40 • Number of events 1 • 96 weeks	0.00% 0/43 • 96 weeks
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/43 • 96 weeks	2.5% 1/40 • Number of events 1 • 96 weeks	0.00% 0/43 • 96 weeks
Musculoskeletal and connective tissue disorders Osteoarthritis	2.3% 1/43 • Number of events 1 • 96 weeks	0.00% 0/40 • 96 weeks	0.00% 0/43 • 96 weeks
Psychiatric disorders Panic attack	0.00% 0/43 • 96 weeks	2.5% 1/40 • Number of events 1 • 96 weeks	0.00% 0/43 • 96 weeks

Other adverse events

Measure	Placebo n=43 participants at risk double-blind, once-weekly subcutaneous injection	Efruxifermin 28 mg n=40 participants at risk double-blind, once-weekly subcutaneous injection	Efruxifermin 50 mg n=43 participants at risk double-blind, once-weekly subcutaneous injection
Gastrointestinal disorders Diarrhea	30.2% 13/43 • 96 weeks	57.5% 23/40 • 96 weeks	44.2% 19/43 • 96 weeks
Gastrointestinal disorders Nausea	30.2% 13/43 • 96 weeks	40.0% 16/40 • 96 weeks	44.2% 19/43 • 96 weeks
Infections and infestations COVID-19	30.2% 13/43 • 96 weeks	25.0% 10/40 • 96 weeks	37.2% 16/43 • 96 weeks
General disorders injection-site erythema	18.6% 8/43 • 96 weeks	25.0% 10/40 • 96 weeks	18.6% 8/43 • 96 weeks
Gastrointestinal disorders Vomiting	16.3% 7/43 • 96 weeks	20.0% 8/40 • 96 weeks	18.6% 8/43 • 96 weeks
Metabolism and nutrition disorders Increased appetite	7.0% 3/43 • 96 weeks	20.0% 8/40 • 96 weeks	23.3% 10/43 • 96 weeks
General disorders Injection-site bruising	16.3% 7/43 • 96 weeks	20.0% 8/40 • 96 weeks	14.0% 6/43 • 96 weeks
Injury, poisoning and procedural complications Procedural pain	16.3% 7/43 • 96 weeks	20.0% 8/40 • 96 weeks	11.6% 5/43 • 96 weeks
Gastrointestinal disorders Abdominal pain	11.6% 5/43 • 96 weeks	17.5% 7/40 • 96 weeks	14.0% 6/43 • 96 weeks
Respiratory, thoracic and mediastinal disorders Cough	14.0% 6/43 • 96 weeks	15.0% 6/40 • 96 weeks	14.0% 6/43 • 96 weeks
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	14.0% 6/43 • 96 weeks	12.5% 5/40 • 96 weeks	16.3% 7/43 • 96 weeks
Nervous system disorders Headache	14.0% 6/43 • 96 weeks	15.0% 6/40 • 96 weeks	11.6% 5/43 • 96 weeks
Metabolism and nutrition disorders Type 2 diabetes	18.6% 8/43 • 96 weeks	10.0% 4/40 • 96 weeks	9.3% 4/43 • 96 weeks
Infections and infestations Sinusitis	16.3% 7/43 • 96 weeks	7.5% 3/40 • 96 weeks	11.6% 5/43 • 96 weeks
Vascular disorders Hypertension	2.3% 1/43 • 96 weeks	20.0% 8/40 • 96 weeks	11.6% 5/43 • 96 weeks
Infections and infestations Nasopharyngitis	14.0% 6/43 • 96 weeks	15.0% 6/40 • 96 weeks	2.3% 1/43 • 96 weeks
Gastrointestinal disorders Abdominal pain, upper	11.6% 5/43 • 96 weeks	5.0% 2/40 • 96 weeks	9.3% 4/43 • 96 weeks
Gastrointestinal disorders Constipation	7.0% 3/43 • 96 weeks	12.5% 5/40 • 96 weeks	7.0% 3/43 • 96 weeks
Gastrointestinal disorders Abdominal distension	7.0% 3/43 • 96 weeks	7.5% 3/40 • 96 weeks	9.3% 4/43 • 96 weeks
Gastrointestinal disorders Frequent bowel movements	2.3% 1/43 • 96 weeks	22.5% 9/40 • 96 weeks	0.00% 0/43 • 96 weeks
Gastrointestinal disorders Flatulence	7.0% 3/43 • 96 weeks	10.0% 4/40 • 96 weeks	2.3% 1/43 • 96 weeks
Gastrointestinal disorders Gastrooesophageal reflux disease	2.3% 1/43 • 96 weeks	12.5% 5/40 • 96 weeks	4.7% 2/43 • 96 weeks
Gastrointestinal disorders Toothache	2.3% 1/43 • 96 weeks	7.5% 3/40 • 96 weeks	7.0% 3/43 • 96 weeks
Gastrointestinal disorders Dry mouth	2.3% 1/43 • 96 weeks	10.0% 4/40 • 96 weeks	0.00% 0/43 • 96 weeks
Gastrointestinal disorders Abdominal tenderness	0.00% 0/43 • 96 weeks	7.5% 3/40 • 96 weeks	0.00% 0/43 • 96 weeks
Infections and infestations Influenza	11.6% 5/43 • 96 weeks	2.5% 1/40 • 96 weeks	4.7% 2/43 • 96 weeks
Infections and infestations Urinary tract infection	4.7% 2/43 • 96 weeks	10.0% 4/40 • 96 weeks	2.3% 1/43 • 96 weeks
General disorders Fatigue	11.6% 5/43 • 96 weeks	10.0% 4/40 • 96 weeks	7.0% 3/43 • 96 weeks
General disorders Injection site pruritus	4.7% 2/43 • 96 weeks	10.0% 4/40 • 96 weeks	14.0% 6/43 • 96 weeks
General disorders Injection-site reaction	7.0% 3/43 • 96 weeks	12.5% 5/40 • 96 weeks	7.0% 3/43 • 96 weeks
General disorders Injection-site rash	2.3% 1/43 • 96 weeks	7.5% 3/40 • 96 weeks	14.0% 6/43 • 96 weeks
General disorders Early satiety	7.0% 3/43 • 96 weeks	7.5% 3/40 • 96 weeks	2.3% 1/43 • 96 weeks
General disorders Swelling face	0.00% 0/43 • 96 weeks	0.00% 0/40 • 96 weeks	7.0% 3/43 • 96 weeks
Metabolism and nutrition disorders Hypoglycaemia	11.6% 5/43 • 96 weeks	12.5% 5/40 • 96 weeks	2.3% 1/43 • 96 weeks
Metabolism and nutrition disorders Decreased appetite	2.3% 1/43 • 96 weeks	7.5% 3/40 • 96 weeks	4.7% 2/43 • 96 weeks
Musculoskeletal and connective tissue disorders Back pain	11.6% 5/43 • 96 weeks	12.5% 5/40 • 96 weeks	14.0% 6/43 • 96 weeks
Musculoskeletal and connective tissue disorders Muscle spasms	9.3% 4/43 • 96 weeks	12.5% 5/40 • 96 weeks	9.3% 4/43 • 96 weeks
Musculoskeletal and connective tissue disorders Arthralgia	11.6% 5/43 • 96 weeks	10.0% 4/40 • 96 weeks	7.0% 3/43 • 96 weeks
Musculoskeletal and connective tissue disorders Pain in extremity	7.0% 3/43 • 96 weeks	2.5% 1/40 • 96 weeks	4.7% 2/43 • 96 weeks
Musculoskeletal and connective tissue disorders Myalgia	7.0% 3/43 • 96 weeks	0.00% 0/40 • 96 weeks	4.7% 2/43 • 96 weeks
Injury, poisoning and procedural complications Contusion	11.6% 5/43 • 96 weeks	5.0% 2/40 • 96 weeks	9.3% 4/43 • 96 weeks
Injury, poisoning and procedural complications Fall	11.6% 5/43 • 96 weeks	5.0% 2/40 • 96 weeks	4.7% 2/43 • 96 weeks
Injury, poisoning and procedural complications Post-traumatic pain	0.00% 0/43 • 96 weeks	7.5% 3/40 • 96 weeks	4.7% 2/43 • 96 weeks
Nervous system disorders Dizziness	9.3% 4/43 • 96 weeks	5.0% 2/40 • 96 weeks	4.7% 2/43 • 96 weeks
Nervous system disorders Migraine	7.0% 3/43 • 96 weeks	2.5% 1/40 • 96 weeks	7.0% 3/43 • 96 weeks
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.0% 3/43 • 96 weeks	5.0% 2/40 • 96 weeks	9.3% 4/43 • 96 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	9.3% 4/43 • 96 weeks	0.00% 0/40 • 96 weeks	4.7% 2/43 • 96 weeks
Respiratory, thoracic and mediastinal disorders Nasal congestion	9.3% 4/43 • 96 weeks	5.0% 2/40 • 96 weeks	0.00% 0/43 • 96 weeks
Skin and subcutaneous tissue disorders Pruritus	4.7% 2/43 • 96 weeks	10.0% 4/40 • 96 weeks	4.7% 2/43 • 96 weeks
Skin and subcutaneous tissue disorders Rash	2.3% 1/43 • 96 weeks	10.0% 4/40 • 96 weeks	7.0% 3/43 • 96 weeks
Psychiatric disorders Depression	4.7% 2/43 • 96 weeks	5.0% 2/40 • 96 weeks	9.3% 4/43 • 96 weeks
Psychiatric disorders Anxiety	0.00% 0/43 • 96 weeks	12.5% 5/40 • 96 weeks	4.7% 2/43 • 96 weeks
Renal and urinary disorders Nephrolithiasis	0.00% 0/43 • 96 weeks	7.5% 3/40 • 96 weeks	4.7% 2/43 • 96 weeks
Blood and lymphatic system disorders Anemia	7.0% 3/43 • 96 weeks	2.5% 1/40 • 96 weeks	0.00% 0/43 • 96 weeks
Hepatobiliary disorders Hepatic cirrhosis	4.7% 2/43 • 96 weeks	7.5% 3/40 • 96 weeks	7.0% 3/43 • 96 weeks

Additional Information

Kitty Yale

Akero Therapeutics, Inc.

Phone: (650) 487-6488

Email: harmonystudies@akerotx.com

Results disclosure agreements

• Principal investigator is a sponsor employee Following the first publication of the Study results by Sponsor, or if a publication is not submitted within 18 months after conclusion, the Investigator may publish or present the results of Institution's and Investigator's activities conducted under this Agreement. Investigator agrees to submit any proposed publication or presentation to Sponsor for review at least 90 days prior to submitting.
• Publication restrictions are in place

Restriction type: OTHER