SOUTH SAN FRANCISCO, Calif.—Akero Therapeutics Inc., a cardio-metabolic, non-alcoholic steatohepatitis (NASH) company developing medicines designed to restore metabolic balance, recently announced the publication of data in the journal Cell Reports Medicine from a Phase 1 clinical trial of efruxifermin (EFX, formerly AKR-001), a fibroblast growth factor 21 (FGF21) analog. The data demonstrated its potential to modulate biomarkers associated with metabolic diseases, including NASH.
In the article, titled “AKR-001, an Fc-FGF21 analog, showed sustained pharmacodynamic effects on insulin sensitivity and lipid metabolism in type 2 diabetes patients,” researchers reported that EFX demonstrated a sufficiently prolonged half-life of 3 to 3.5 days to support weekly dosing. In addition, with a variation in systemic concentration of only twofold when dosed weekly, treatment with EFX delivered larger and more consistent improvements in markers of insulin sensitivity and lipid metabolism than previously reported for FGF21 analogs, and it was reported to be generally well tolerated. Weekly administration of 70 mg demonstrated larger metabolic effects than dosing every other week with 140 mg, even though exposure to EFX was comparable.
“Efruxifermin is the first FGF21 analog to demonstrate a pharmacokinetic profile that would enable sustained, balanced agonism across all of FGF21’s receptors with once weekly dosing,” said Dr. Tim Rolph, chief scientific officer and co-founder of Akero, as well as senior author of the manuscript.
Added Dr. Andrew Cheng, president and CEO of Akero: “The data reported in this study provided the rationale for evaluating the efficacy and safety of EFX in NASH patients in our Phase 2a BALANCED study, which met all endpoints. Our recent readouts of liver fat reductions and improvements in histological measures showed the largest reductions in liver fat and improvements in liver histology reported to date and confirm the promising clinical profile of EFX.”
In patients dosed weekly with 70 mg EFX in the Phase 1 study, treatment was associated with an increase in insulin sensitivity as demonstrated by reductions in HOMA-IR. This enhancement of insulin sensitivity by EFX was replicated in NASH subjects and associated with better glycemic control, as recently disclosed for the BALANCED study. Treatment with EFX in the Phase 1 study was associated with amelioration of dyslipidemia, prevalent among type 2 diabetes and NASH patients, who are susceptible to cardiovascular disease. An improved lipoprotein profile was also evident with EFX treatment in the BALANCED study.
Efruxifermin is Akero’s lead product candidate for NASH, engineered to mimic the biological activity of native FGF21. EFX is designed to reduce liver fat and inflammation, reverse fibrosis, increase insulin sensitivity and improve lipoproteins. This holistic approach reportedly offers the potential to address the complex, multisystem disease state of NASH, including improvements in lipoprotein risk factors linked to cardiovascular disease—the leading cause of death in NASH patients.