Publication of phase IIb SYMMETRY cohort D study in Clinical Gastroenterology and Hepatology- Akero Therapeutics Inc.

The publication, available online, reports results of the 12-week study to assess safety and tolerability of efruxifermin (EFX) compared to placebo when added to a stable dose of GLP-1 receptor agonist (GLP-1RA) in patients with Type 2 diabetes (T2D) and F1-F3 liver fibrosis due to metabolic dysfunction-associated steatohepatitis (MASH), formerly known as NASH.

Tolerability of EFX on top of GLP-1RA (N=21 patients) was generally comparable to GLP-1RA alone (placebo, N=10). The most frequent adverse events for EFX-treated patients were grade 1 or 2 gastrointestinal events (diarrhea, nausea, and increased appetite). One patient treated with EFX discontinued due to nausea and one EFX-treated patient withdrew consent prior to Week 12. There were no drug-related serious adverse events.

The overall tolerability profile was similar to that observed in Akero’s prior BALANCED and HARMONY studies in patients with MASH (F1-F3). Patients treated with EFX plus GLP-1RA showed a similar mean weight loss from baseline relative to patients treated with GLP-1RA alone.

Non-invasive markers of liver health showed clinically meaningful improvements following treatment for 12 weeks with EFX plus GLP-1RA compared to GLP-1RA alone (placebo). Notably, liver fat was reduced from baseline by 65% for EFX on top of GLP-1RA compared to a 10% relative reduction for GLP-1RA alone, with levels normalized (5% absolute) in almost 90% of patients receiving EFX plus GLP-1RA compared to 10% of those receiving GLP-1RA alone. In addition, patients treated with EFX plus GLP-1RA (N=21) had greater improvements in non-invasive markers of liver injury (ALT and AST) and fibrosis (Pro-C3 and ELF), than those receiving GLP-1RA alone (N=10). Markers of glycemic control and lipid metabolism were also improved more with EFX plus GLP-1RA than GLP-1RA alone, reflecting the complementary insulin-sensitizing action of EFX when combined with an insulin secretagogue such as GLP-1RA.

“We believe these data indicate that EFX could be an important treatment option for patients with MASH who are already receiving GLP-1RA for T2D or obesity,” said Kitty Yale, chief development officer of Akero. “We look forward to continuing the development and assessment of EFX in our Phase III SYNCHRONY Histology and SYNCHRONY Real-World studies which are currently enrolling patients including those on stable GLP-1RA therapy.”

See- "Safety and Efficacy of Efruxifermin in Combination With a GLP-1 Receptor Agonist in Patients With NASH/MASH and Type 2 Diabetes in a Randomized Phase II Study"; Stephen A. Harrison, Juan P. Frias, K. Jean Lucas, Timothy Rolph, Andrew Cheng, Kitty Yale. Published: March 04, 2024DOI:https://doi.org/10.1016/j.cgh.2024.02.022.in Clinical Gastroenterology and Hepatology.