Akero(AKRO) - 2024 Q4 - Annual Results

Efruxifermin (EFX) Efficacy and Safety - Efruxifermin (EFX) demonstrated unprecedented fibrosis improvement after 96 weeks of treatment, with a 39% improvement in completer analysis versus 15% for placebo[10]. - The Phase 2b SYMMETRY study reported the first-ever statistically significant reversal of cirrhosis, with 29% of patients showing improvement compared to 12% for placebo[10]. - 50mg EFX treatment resulted in a 50% improvement in fibrosis with no worsening of MASH at Week 96, compared to 12% in the placebo group[57]. - 70% of patients receiving EFX 28mg and 50mg achieved MASH resolution at Week 96, significantly higher than the 13% in the placebo group[68]. - EFX 50mg achieved a 75% response rate for ≥1 stage fibrosis improvement at Week 96, significantly higher than the placebo[121]. - EFX 50mg demonstrated a 23% improvement in fibrosis at Week 96 compared to 2% in the placebo group, with statistical significance (p<0.01)[130]. - 68% of patients with F3 fibrosis at baseline showed ≥2 stage improvement in fibrosis with EFX 50mg, while only 14% in the placebo group achieved this[137]. - EFX 50mg resulted in a 60% rate of ≥1 stage fibrosis improvement and MASH resolution at Week 96, significantly higher than the 9% in the placebo group (p<0.01)[152]. - EFX 50mg treatment group achieved a significant liver fat reduction of 65% compared to a 9% reduction in the placebo group at Week 12, p<0.001[186]. - 90% of patients in the EFX 50mg group achieved a ≥50% relative reduction in liver fat, compared to 10% in the placebo group, p<0.001[192]. - The EFX 50mg group showed a reduction in liver stiffness by 2.7 kPa, while the placebo group showed no significant change[196]. - EFX 50mg treatment resulted in a decrease in ALT levels from a baseline of 35 U/L to a reduction of 5.3 U/L, while the placebo group showed an increase[200]. Clinical Trials and Study Design - The Phase 3 SYNCHRONY program is actively enrolling patients, with a total of approximately 3,500 participants across three studies focusing on different fibrosis stages[24]. - The SYNCHRONY program includes a comprehensive evaluation of safety, tolerability, and efficacy, with primary endpoints focused on fibrosis improvement and MASH resolution[24]. - The company plans to report results for the primary endpoints of the SYNCHRONY studies in the first half of 2026 and 2027[25]. - The Phase 3 studies are expected to provide critical data on the long-term clinical outcomes and safety of EFX in a broad patient population[24]. - The total treatment duration for the Phase 3 SYNCHRONY trial is approximately 260 weeks, with a randomization of 1:1 for EFX 50mg and placebo[96]. - The study included a total of 1150 patients, with a focus on compensated cirrhosis due to MASH[96]. Safety and Adverse Events - Treatment-emergent adverse events (TEAEs) leading to discontinuation were 3% in placebo, 11% in EFX 28mg, and 18% in EFX 50mg[71]. - The most frequent drug-related treatment-emergent adverse events (TEAEs) included diarrhea (40% for EFX 28mg and 37% for EFX 50mg)[158]. - No deaths were reported in any treatment group, with serious adverse events occurring in 9% of placebo, 10% of EFX 28mg, and 16% of EFX 50mg groups[158]. - 33% of patients in the EFX 50mg group experienced nausea as a treatment-emergent adverse event, compared to 10% in the placebo group[183]. - 5% of patients in the EFX 50mg group discontinued treatment due to drug-related adverse events[183]. Demographics and Baseline Characteristics - As of December 31, 2024, the company has approximately $800 million in cash, sufficient to fund the Phase 3 SYNCHRONY studies through their primary endpoints into the second half of 2027[36]. - The baseline demographics showed that 82% of patients had type 2 diabetes, with an average age of 61 years across the study population[49]. - The baseline demographics indicated that 70% of the placebo group had fibrosis stage F3, while the EFX 50mg group had 63%[110]. - The baseline hepatic fat fraction was 11% in the EFX 50mg group compared to 15% in the placebo group[179]. - 76% of patients in the EFX 50mg group were on Metformin, compared to 70% in the placebo group[181].