S2805 The Use of Non-Invasive Tests to Characterise the Total Baseline Population in the Phase 3 Essence Trial

Introduction: ESSENCE is an ongoing phase 3 trial (NCT04822181) in participants with biopsy-defined, non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH). In part 1, the primary histological endpoints were met in the first 800 randomized participants after 72 weeks’ treatment with semaglutide 2.4 mg. The aim of this post hoc analysis was to characterize the total randomized, baseline population using selected non-invasive tests (NITs). Methods: Randomized participants (N = 1197) were characterized by NITs at baseline: vibration-controlled transient elastography liver stiffness measurement (VCTE LSM; FibroScan), enhanced liver fibrosis (ELF) score, FibroScan-aspartate aminotransferase (FAST) score and Fibrosis-4 index (FIB-4) score. Eligible participants had histologically defined MASH and liver fibrosis stage 2 or 3. Clinical NIT categories for moderate-to-advanced fibrosis were used to group participants, and descriptive statistics determined numbers of participants in each NIT category and demographics. Results: At baseline, 95.5% fulfilled NIT scores in ≥1 of the guideline-recommended ranges for FIB-4 (≥1.3 – ≤2.67), ELF (≥9.0 – <11.3) or VCTE LSM (≥8.0 – <20.0 kPa). Most had a FAST score ≥0.35 (82.4%) and 34.7% had a FIB-4 score <1.3. As expected, participants with FIB-4 score <1.3 were younger (mean age: 48.1 years) than those with FIB-4 score ≥1.3 – ≤2.67 (59.1 years) and >2.67 (63.7 years). They also had a higher mean BMI (36.7 kg/m2) and were more likely to be men than those with FIB-4 score ≥1.3. Of those with a baseline FIB-4 measurement outside the guideline-recommended category for moderate-to-advanced fibrosis (n = 480), 91.3% had other NITs within the guideline-recommended category (ELF score ≥9.0 – <11.3 or VCTE LSM ≥8.0 – < 20.0 kPa). Of note, 27.6% of participants had ≥1 NIT score that was above the guideline-recommended limit, however, only 1.3% had values above the upper limits of all NITs. Additionally, those with VCTE LSM scores ≥20.0 kPa had a higher mean BMI (38.5 kg/m2) and were more likely to have type 2 diabetes (61.0%) than those with VCTE LSM <20.0 kPa. Conclusion: While participants in ESSENCE had biopsy-defined stage 2 or 3 fibrosis, the population had a broad range of NIT values. If there is a clinical suspicion for MASH with moderate fibrosis, use of multiple NITs may support a clinical diagnosis of MASH.