Akero Therapeutics (AKRO) Study Result summary

Study background and design

• SYMMETRY was a phase 2b, randomized, double-blind, placebo-controlled, multi-center, dose-ranging trial evaluating EFX in adults with biopsy-proven compensated cirrhosis (F4, Child-Pugh A) due to MASH.

• 182 patients were enrolled and randomized to receive weekly subcutaneous 20, 28, or 50 mg EFX or placebo; primary endpoint was ≥1-stage fibrosis improvement without MASH worsening at week 36, with continued treatment and biopsy at week 96.

• 87% of patients with week 36 biopsies remained on study through week 96, with high retention across groups.

Efficacy results

• At week 96, 39% of patients on 50 mg EFX achieved fibrosis improvement without MASH worsening, versus 15% for placebo (p<0.01); ITT analysis showed 29% vs 12%.

• Sustained response was seen in 75% of week 36 responders on 50 mg EFX at week 96, and 26% of week 36 non-responders became responders by week 96.

• MASH resolution rate for 50 mg EFX was 55%, about three times placebo, with statistical significance in ITT analysis.

• Baseline GLP-1 therapy did not impact cirrhosis reversal; response rate in non-GLP-1 subgroup was 45% for EFX vs 17% for placebo.

• Effect size more than doubled from week 36 (10%) to week 96 (24%) in the 50 mg group, highlighting benefit of longer treatment.

Safety and tolerability

• No deaths occurred with EFX; one death in placebo group due to pneumonia.

• No serious adverse events were attributed to EFX; most common adverse events were mild to moderate, transient gastrointestinal symptoms.

• Bone mineral density declined 5% over 96 weeks for EFX, similar to placebo; fracture rates were equal between groups.

• No significant changes in ECGs, heart rate, or blood pressure; body weight reduced ~2% in both groups.