PMID-39412509 — ESSENCE: Baseline Characteristics and Design Paper (Aliment Pharmacol Ther 2024)

[DRAFT — authored 2026-04-19. Citation verified against PubMed/Wiley 2026-04-19.]

Citation

Newsome PN, Sanyal AJ, Kliers I, Østergaard LH, Harrison SA; ESSENCE Study Group. Semaglutide 2.4 mg in Participants With Metabolic Dysfunction-Associated Steatohepatitis: Baseline Characteristics and Design of the Phase 3 ESSENCE Trial. Aliment Pharmacol Ther. 2024;60(11-12):1525-1537. doi: 10.1111/apt.18331. PMID: 39412509. PMCID: PMC11599791.

External URL: PubMed

Study Design

Trial name: ESSENCE (NCT04822181)
Type: Phase 3 randomized, multicenter, double-blind, placebo-controlled trial
Design: Two-part study
- Part 1: 72-week primary analysis on liver histology (reported as PMID: 40305708)
- Part 2: 240-week follow-up with end-of-treatment liver biopsy for long-term outcomes
N: 1,197 enrolled
Randomization: 2:1 semaglutide 2.4 mg SC weekly vs placebo
Inclusion: Biopsy-proven MASH (previously NASH) with fibrosis F2 or F3
Exclusion: F4 cirrhosis, other chronic liver disease, decompensated liver disease
Dual primary endpoints: Resolution of steatohepatitis without worsening fibrosis; reduction in fibrosis without worsening steatohepatitis

Baseline Characteristics (key descriptors)

Of 800 in the interim analysis, 250 (31.3%) had F2 fibrosis and 550 (68.8%) had F3 fibrosis
Mean age ~55-56 years across arms
~58% female
Mean BMI and metabolic comorbidity profile consistent with MASH population
T2D prevalence: substantial minority (not stratified primary; pre-specified subgroup)

Key Findings (from design paper)

Methodology paper: trial design, endpoint definitions, randomization, and baseline characteristics
Pre-specifies the analysis approach for Part 1 (72-week histology primary) and Part 2 (240-week outcomes including liver-related events and mortality)
Establishes the precedent that MASH Phase 3 trials can use co-primary liver-histology endpoints (resolution + fibrosis) — FDA-concordant framework

Clinical Relevance

ESSENCE design paper is the methodological reference for the Phase 3 trial that resulted in FDA MASH approval for semaglutide (August 2025). Core points:

Methodology reference — clinicians and researchers citing ESSENCE in educational materials should reference both the design/baseline paper (this PMID: 39412509) and the primary results paper (PMID: 40305708).
F2/F3 population selection — ESSENCE excludes F4 cirrhosis; this is important context for the distinct Loomba 2023 Phase 2 cirrhosis trial (different population, different biology, primary endpoint not met).
240-week long-term outcomes pending — Part 2 will provide the evidence on liver-related events, cirrhosis progression, and mortality that ultimately determines whether MASH resolution translates to clinical outcome benefit.

Linked Peptides

Semaglutide

Related Lessons

Lesson 5.2 — Semaglutide Deep Dive (MASH section, trial design reference)
Lesson 5.4 — MASH pipeline context

Related Studies

PMID-40305708 – ESSENCE Sanyal Newsome Semaglutide MASH Phase 3 — primary results companion

PMID-39412509 – ESSENCE Design Baseline Characteristics