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 strong results of our Phase 1 and 2 studies, we initiated our SYNCHRONY Phase 3 program. Enrollment for the first two trials, SYNCHRONY Histology and SYNCHRONY Real-World, is currently under way and ongoing.
SYNCHRONY
STATUS: ongoing
The Phase 3 SYNCHRONY clinical trial program consists of three trials, two of which have started enrolling patients and the third to be initiated in Q2’24. The first two trials under way are parallel, randomized, placebo-controlled trials: SYNCHRONY Histology evaluating the efficacy and safety of EFX in patients with biopsy-confirmed pre-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH), and SYNCHRONY Real-World assessing safety and tolerability of EFX in patients with non-invasively diagnosed MASH or metabolic dysfunction-associated steatotic liver disease (MASLD).
SYNCHRONY Histology is expected to enroll approximately 1,000 patients with biopsy-confirmed MASH, fibrosis stage 2 or 3 (F2-F3) to receive weekly injections of EFX 28mg, EFX 50mg, or placebo. The primary endpoint, to support an application for accelerated approval, is the proportion of patients experiencing ≥ 1-stage fibrosis improvement AND resolution of MASH after 52 weeks of treatment. After 52 weeks, patients will continue treatment as randomized in SYNCHRONY Histology to be followed for long-term clinical outcomes, such as progression to cirrhosis. SYNCHRONY Real-World is expected to enroll approximately 600 patients with MASH or MASLD diagnosed by non-invasive tests to receive weekly injections of EFX 50mg or placebo. The primary endpoint of safety and tolerability will be assessed after 52 weeks of treatment. Key secondary endpoints in both the Histology and Real-World studies include changes from baseline in markers of liver injury and fibrosis, glycemic control and lipids.
In all EFX Phase 3 studies, patients will self-administer EFX using the LyoJect 3S dual chamber syringe, a pre-filled device intended for commercial use in the event EFX is approved for marketing. This optimized formulation delivers blood levels of EFX comparable to those of the liquid formulation used in prior clinical studies.
Read more at Clinicaltrials.gov: SYNCHRONY Histology and SYNCHRONY Real-World.
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 MASH, 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 MASH – from compensated cirrhosis (F4) to F1 or F2, compared with 0% for placebo. Statistically significant rates of MASH 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 MASH 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.
Results from the expansion cohort of the Phase 2b SYMMETRY study, known as Cohort D, were shared in June 2023. The study met safety and tolerability endpoints and showed adding EFX to GLP-1 therapy significantly improved non-invasive markers of MASH, offering benefit over GLP-1 receptor agonist (GLP-1) therapy alone. EFX was reported to be generally well tolerated in Cohort D with comparable results for the EFX (N=21) and placebo (N=10) groups. The overall tolerability profile was similar to that observed in Akero’s BALANCED and HARMONY studies. Cohort D also met all key secondary endpoints, including relative reduction of liver fat and proportion of patients whose absolute liver fat level normalized to 5 percent or less.
Read more at ClinicalTrials.gov.
HARMONY
STATUS: completed
The 96-week Phase 2b HARMONY study is a multi-center, randomized, double-blind, placebo-controlled, clinical trial that enrolled 128 biopsy-confirmed MASH 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 ≥1 stage improvement in fibrosis with no worsening of MASH after 24 weeks of treatment for both the 50mg EFX (41%) and 28mg EFX (39%) dose groups, compared to 20% for the placebo arm.
At the week 96 readout, which occurred in March 2024, the response rates on this endpoint increased to 75% (p<0.001) for 50mg EFX and 46% (p=0.07) for 28mg EFX, compared to 24% for placebo. The study also demonstrated additional improvements on histology endpoints at week 96—notably 36% (p<0.01) and 31% (p<0.01) of patients treated with 50mg EFX and 28mg EFX experienced a 2-stage improvement in fibrosis without worsening of MASH—more than 10-fold the placebo rate of 3%. 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.
Analysis of the evolution of responses between weeks 24 and 96 indicated not only broader fibrosis improvement without worsening of MASH but also sustained response, particularly at 50mg EFX. Among those patients with available week 96 biopsies whose fibrosis improved at week 24, 92% and 83% of the 50mg and 28mg EFX groups remained responders, respectively, compared to 40% for placebo.
Read more at ClinicalTrials.gov.
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 MASH 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.
