Safety and efficacy of efruxifermin in metabolic dysfunction-associated steatohepatitis: A systematic review

Table 1 Baseline characteristics of individual studies and study participants included in the meta-analysis, mean ± SD

Ref.	Study design, name of the trial, trial registration number	Major inclusion criteria	Groups	Number of study subjects	Female (%)	T2D (%)	Age (year)	BMI (kg/m2)	Hepatic parameters	Concomitant medications (%)	Duration
Harrison et al[21], 2021, Multicenter in United States	Phase 2a RCT, BALANCED, NCT03976401	Adults with biopsy-proven NASH, fibrosis stage 1–3, NAS ≥ 4, HFF ≥ 10% and E > 7.0 kPa	EFX 28 mg	19	53	37	50.4 ± 12.4	38.8 ± 9.3	HFF: 21.4 ± 8.1; NAS: 5.6 ± 1.0; ELF: 9.5 ± 0.6	MFN (37), Statin (32)	12 weeks
			EFX 50 mg	20	50	50	52.6 ± 14.2	36.7 ± 6.8	HFF: 18.3 ± 6.3; NAS: 5.1 ± 1.2; ELF: 9.5 ± 0.9	MFN (42), Statin (37)
			EFX 70 mg	20	55	50	53 ± 13.2	37.2 ± 5.5	HFF: 19.4 ± 6.3; NAS: 5.6 ± 0.7; ELF: 9.5 ± 0.8	MFN (25), Statin (45)
			Placebo	21	71	67	52.4 ± 9.6	37.6 ± 4.8	HFF: 19.3 ± 6.9; NAS: 5.1 ± 1.0; ELF: 9.5 ± 1.0	MFN (48), Statin (33)
Harrison et al[22], 2023, Multicenter in United States	Phase 2a RCT, BALANCED (expansion cohort), NCT03976401	Adults with biopsy-confirmed compensated cirrhosis due to NASH, E > 13.1 kPa, ELF > 9.8, and no evidence of worsening levels of ALT and AST	EFX 50 mg	20	80	50	61.1 ± 10	36.0 ± 5.6	E: 22.1 ± 10.8 kPa; NAS: 4.1 ± 1.7; ELF: 10.4 ± 1.2	GLP-1RA (15), Statin (30)	16 weeks
			Placebo	10	30	50	57.1 ± 14.4	39.1 ± 8.3	E: 25.8 ± 13.2 kPa; NAS: 3.3 ± 2.1; ELF: 9.7 ± 0.8	GLP-1RA (30), Statin (30)
Harrison et al[23], 2023, Multicenter in United States	Phase 2b RCT, HARMONY, NCT04767529	Adults with biopsy-confirmed NASH, defined by NAS ≥ 4 and scores of 1 or higher in each of steatosis, ballooning, and lobular inflammation, with histological stage F2 or F3 fibrosis	EFX 28 mg	42	69	76.2	56.5 ± 9.3	38.3 ± 6.9	HFF: 18.5 ± 6.9; E: 13.8 ± 5.2 kPa; NAS: 5.1 ± 1.0; ELF: 9.7 ± 0.8	GLP-1RA (12), SGLT-2i (14), Statin (52.4)	96 weeks
			EFX 50 mg	43	54	69.8	52.4 ± 11.4	37.2 ± 6.6	HFF: 17.5 ± 6.4; E: 16.0 ± 7.1 kPa; NAS: 5.6 ± 1.1; ELF: 9.8 ± 0.8	GLP-1RA (9), SGLT-2i (12), Statin (32.6)
			Placebo	43	63	65.1	55.0 ± 10.1	38.7 ± 7.7	HFF: 17.1 ± 6.4; E: 14.5 ± 6.2 kPa; NAS: 5.4 ± 1.2; ELF: 9.8 ± 0.7	GLP-1RA (16), SGLT-2i (19), Statin (48.8)
Harrison et al[24], 2025, Multicenter in United States	Phase 2b RCT, Cohort D, NCT05039450	Adults with MASH, F1 to F3 (confirmed by biopsy), and T2D treated with a stable dose of GLP-1RA	EFX 50 mg	21	43	100	59	35.0	HFF: 10.4; E: 10 kPa; ELF: 9.2	GLP-1RA (100), MFN (76), SGLT-2i (33), Statin (81)	12 weeks
			Placebo	10	90	100	55	35.4	HFF: 15.2; E: 12 kPa; ELF: 9.6	GLP-1RA (100), MFN (70), SGLT-2i (20), Statin (50)
Noureddin et al[25], 2025, Multicenter in United States, Puerto, Rico, and Mexico	Phase 2b RCT, SYMMETRY, NCT05039450	Adults with liver histologic features consistent with MASH and compensated cirrhosis (defined as stage 4 fibrosis with a Child-Pugh score of 5 or 6, T2D or two components of MetS	EFX 28 mg	57	68	81	61.7 ± 8.3	36.1 ± 7.1	E: 24.1 ± 12.4 kPa; NAS: 3.9 ± 1.6; ELF: 10.6 ± 0.8	GLP-1RA (19)	96 weeks
			EFX 50 mg	63	70	78	59.4 ± 8.8	34.5 ± 5.9	E: 24.5 ± 13.4 kPa; NAS: 4.1 ± 1.5; ELF: 10.5 ± 0.8	GLP-1RA (33)
			Placebo	61	62	82	61 ± 7.5	36.7 ± 6.8	E: 24.7 ± 14.2 kPa; NAS: 3.7 ± 1.6; ELF: 10.4 ± 0.8	GLP-1RA (26)

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index; E: Liver stiffness during FibroScan measurement; EFX: Efruxifermin; ELF: Enhanced liver fibrosis; GLP-1RA: Glucagon-like peptide-1 receptor agonists; HFF: Hepatic fat fraction (by Magnetic Resonance Imaging Proton Density Fat Fraction); kPa: Kilopascals; MASH: Metabolic dysfunction-associated steatohepatitis; MetS: Metabolic syndrome; NAS: Non-alcoholic fatty liver disease activity score; NASH: Nonalcoholic steatohepatitis; MFN: Metformin; RCT: Randomized controlled trial; SGLT-2i: Sodium-glucose cotransporter 2 inhibitor; T2D: Type 2 diabetes.