Efruxifermin reduces liver fat in NASH

Efruxifermin, a fibroblast growth factor-21 analog, helped patients with non-alcoholic steatohepatitis achieve reductions in liver fat and improved liver histology, lipid metabolism and glycemic control, according to research presented at The Liver Meeting Digital Experience.

Stephen A. Harrison, MD, from Pinnacle Clinical Research, and colleagues conducted the phase 2a BALANCED study, a randomized controlled trial comprising 80 patients with biopsy confirmed NASH to assess the safety, efficacy and pharmacokinetics of Efruzifermin (EFX, Akero Therapeutics).

In the study, investigators randomly assigned patients to received either 28, 50 or 70 mg of EFX, or placebo, subcutaneously once weekly for 16 weeks. The primary endpoint of the trials was absolute change in liver fat measured by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) at week 12. Patients who achieved at least 30% relative reduction in liver fat were eligible for an end-of study biopsy used to evaluate change in fibrosis and NAS.

Researchers also assessed safety, tolerability, biomarkers of liver injury and fibrosis, and lipid and glucose metabolism at week 16.

At week 12, all EFX dose groups met the primary endpoint. Of the 80 total patients, 50 achieved an at least 30% reduction in liver fat and were eligible for the end-of-study biopsy.

After 16 weeks of treatment, 48% of patients across all EFX doses achieved at least 1-stage fibrosis improvement with no worsening of NASH, 48% achieved NASH resolution with no worsening of fibrosis and 28% achieved at least 2-stage fibrosis improvement.

Harrison and colleagues found that the 50 and 70 mg EFX groups experienced reductions in HbA1c, as well as decreases in C-peptide across all EFX groups. They also observed a reduction in mean body weight across all drug groups.

Overall, EFX was safe and well-tolerated by patients. The most common adverse events were mild or moderate gastrointestinal events.

“EFX has consistent, robust effects across non-invasive datasets, including liver fat reduction as measured by MRI-PDFF,” Harrison said in his presentation. “EFX is also rectifying several NASH comorbidities, improving glycemic control by enhancing insulin sensitivity, restoring a healthy lipoprotein profile and lowering body weight.”