Efruxifermin Plus GLP-1RA Shows Promise in MASH Treatment

A recent study published in Clinical Gastroenterology and Hepatology indicates that efruxifermin查看药品详情 (EFX), when administered with a glucagon-like peptide-1 receptor agonist (GLP-1RA查看药品详情), presents a well-tolerated and safe dual therapy option for individuals grappling with metabolic dysfunction-associated steatohepatitis (搜索)搜索该疾病 (MASH (搜索)搜索该疾病) and type 2 diabetes (搜索)搜索该疾病 (T2D). The research highlights notable reductions in noninvasive fibrosis markers and hepatic fat fraction (HFF) among patients.

MASH (搜索)搜索该疾病 and Type 2 Diabetes (搜索)搜索该疾病 Complications

Patients with metabolic disorders, such as metabolic dysfunction-associated steatotic liver disease (MASLD), often experience a higher prevalence of T2D and obesity, which can progress to MASH (搜索)搜索该疾病. Studies suggest that fibrosis can advance more rapidly in MASLD patients with T2D compared to those without it. The co-occurrence of these conditions elevates the risk of cardiovascular disease and hepatocellular carcinoma (HCC (搜索)搜索该疾病).

GLP-1RAs and Fibroblast Growth Factor 21查看药品详情

Weight loss, improved insulin sensitivity, and lifestyle adjustments can mitigate these risks, with GLP-1RAs playing a beneficial role. According to the study authors, GLP-1RAs indirectly enhance liver health by decreasing calorie intake and redirecting energy away from the liver through increased peripheral uptake of dietary energy. Fibroblast growth factor 21查看药品详情 (FGF21) also shows promise due to its capacity to regulate lipid and glucose metabolism and reduce cellular stress. Efruxifermin查看药品详情 (EFX), an Fc-FGF21 analog, has demonstrated the ability to address steatosis, liver fibrosis, hepatocyte injury, fibrogenesis, and insulin resistance in MASH (搜索)搜索该疾病 treatment. This led researchers to hypothesize that EFX could augment the pharmacologic impact of GLP-1RAs.

Study Design and Patient Population

The multicenter study, conducted between May and December 2022, involved 31 patients (29 completing the study) from 24 clinics across the US. The 12-week treatment period included a 4-week follow-up. Eligible patients had MASH (搜索)搜索该疾病 and T2D and were on stable GLP-1RA查看药品详情 doses for at least 90 days before screening. Patients with fibrosis stage 4 (F4), HCC (搜索)搜索该疾病 history, liver transplant, or decompensated liver disease were excluded.

Participants were randomized 2:1 to receive either 50 mg of EFX (n = 21) or a placebo (n = 10) weekly, in addition to their GLP-1RA查看药品详情 therapy. Tolerability and safety were assessed through adverse event reports, electrocardiograms, clinical laboratory tests, and immunogenicity assessments. Outcomes related to HFF, fibrosis, insulin sensitivity, weight changes, and liver markers were also evaluated. The average age of patients was 57.4 years, with an average weight of just over 99 kg. The GLP-1RAs used included liraglutide查看药品详情, semaglutide查看药品详情, and dulaglutide查看药品详情.

Key Findings

The most common treatment-emergent adverse event was nausea (33% in the treatment group vs 10% in the placebo group). Other reported events included increased appetite (24% vs 0%), diarrhea (19% vs 30%), and decreased appetite (14% vs 20%). No serious drug-related adverse events occurred, although two participants withdrew. The treatment group had significantly higher baseline heart rates (6 beats/min vs 4 beats/min; P = .0042), but no significant differences in systolic or diastolic blood pressure were observed by week 12. No significant clinical differences were noted in other laboratory tests or safety measures.

After 12 weeks, patients receiving EFX showed significantly lower liver fat levels, with 88% achieving normal HFF levels (≤ 5%) compared to 10% in the placebo group (P = .002). The treatment group's HFF decreased by 65% from baseline, versus 10% in the placebo group (P < .0001). Furthermore, 88% of the treatment group experienced at least a 50% reduction in HFF, compared to 0% in the placebo group (P < .0001).

EFX was associated with improvements in fibrosis, lipid metabolism, glucose levels, and noninvasive liver injury markers, while patients maintained weight loss from their GLP-1RA查看药品详情 therapy.

Conclusion

The authors concluded that combining EFX with GLP-1RAs shows preliminary indications of accelerating MASH (搜索)搜索该疾病 resolution and fibrosis regression.