Clinical Trials Overview
We have designed a robust clinical development program to deliver EFX, if approved, as quickly as possible to patients in need.
Building on the strongly positive results of our Phase 2a BALANCED and week 24 results of the Phase 2b HARMONY (ongoing safety follow-up) studies, EFX is currently undergoing an additional Phase 2b clinical trial: the SYMMETRY study in cirrhotic (F4) patients. Two randomized, placebo-controlled Phase 1 trials were previously completed in diabetic patients. Enrollment for the first two trials of our SYNCHRONY Phase 3 program is expected to begin in the second half of 2023.
BALANCED
STATUS: completed
The BALANCED study was a randomized, placebo-controlled Phase 2a trial across 27 U.S. sites that enrolled 80 biopsy-confirmed, pre-cirrhotic NASH patients (F1 to F3 fibrosis stage) who received either placebo or EFX for 16 weeks as a weekly subcutaneous injection in one of three doses: 28mg, 50mg, or 70mg. The study met its primary endpoint of absolute change from baseline in hepatic fat fraction measured at week 12, with 48 percent of EFX patients across dose groups achieving normal levels of liver fat (defined as less than 5 percent liver fat), compared with 5 percent of placebo patients. Reductions in liver fat were associated with substantial decreases in markers of liver injury and fibrosis. Consistent with these observations, 50 percent of EFX patients who had F2/F3 fibrosis at baseline and repeat biopsies after 16 weeks of treatment achieved a two-stage regression of fibrosis. Reflecting EFX’s potential to have a beneficial impact on whole body metabolism, EFX patients were reported to have significantly improved levels of triglyceride, non-HDL cholesterol and HbA1c, along with a trend toward lower body weight.
Read More at ClinicalTrials.gov.
HARMONY
STATUS: ongoing
The 96-week Phase 2b HARMONY study is a multi-center, randomized, double-blind, placebo-controlled, clinical trial that enrolled 128 biopsy-confirmed NASH patients with fibrosis stage 2 or 3 who received once-weekly subcutaneous dosing of 28mg or 50mg EFX, or placebo. A readout through week 24 data collection occurred in September 2022. The study met its primary endpoint of fibrosis regression at 24 weeks in both dosing groups, with 41% and 39% of EFX-treated patients, respectively, experiencing at least a one-stage improvement in liver fibrosis with no worsening of NASH by week 24, compared with 20% for the placebo arm. The study also met a key secondary endpoint with 76% and 47% of patients treated with 50mg and 28mg, respectively, achieving NASH resolution without worsening of fibrosis, compared with 15% for placebo. The results also demonstrated statistically significant effects in multiple secondary endpoints in both dose groups, including improvements in liver fat, liver enzymes, non-invasive fibrosis markers, HbA1c, lipoproteins, and body weight. Treatment with EFX was generally well-tolerated, with a tolerability profile comparable to that observed in Akero’s Phase 2a BALANCED study.
Patients are continuing to receive EFX or placebo for up to 96 weeks to provide additional data, including a second on-treatment biopsy at week 96.
Read more at ClinicalTrials.gov.
SYMMETRY
STATUS: ongoing
The 96-week Phase 2b SYMMETRY study is a multicenter, randomized, double-blind, placebo-controlled, clinical trial that enrolled 182 patients with biopsy-confirmed compensated cirrhosis (F4), Child-Pugh class A who received once-weekly subcutaneous dosing of 28mg or 50mg EFX, or placebo. The 36-week study readout occurred in October 2023. A trend was observed for the primary endpoint of fibrosis improvement at 36 weeks, with 22% and 24% of the 28mg and 50mg EFX-treated groups, respectively, experiencing at least a one-stage improvement in liver fibrosis and no worsening of NASH, compared with 14% for placebo. In addition, 4% of patients in each of the EFX-treated groups experienced a three- or two-stage fibrosis improvement without worsening of NASH – from compensated cirrhosis (F4) to F1 or F2, compared with 0% for placebo. Statistically significant rates of NASH resolution in 67% and 60% of patients at week 36 were observed for the 28mg and 50mg EFX-treated groups, respectively, compared with 26% for placebo, representing the highest response rates reported to date for NASH resolution in this patient population. Statistically significant improvements were also observed for both EFX groups in non-invasive markers of liver injury and fibrosis, insulin sensitization and lipoproteins. In addition, EFX was reported to be generally well-tolerated.
Patients are continuing to receive EFX or placebo for up to 96 weeks to provide additional data, including a second on-treatment biopsy at week 96.
Read more at ClinicalTrials.gov.
