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Variability in Liver Biopsy Assessment: Data from the Pegozafermin Phase 1b/2a Study in Subjects with Non-Alcoholic Steatohepatitis (NASH)

AASLD 2022

Study Background

• Fibroblast growth factor 21 (FGF21) is an endogenous hormone that regulates Baseline Characteristics - All Subjects lipid and glucose metabolism and energy expenditure.

• Pegozafermin (PGZ) is a glycoPEGylated FGF21 analog with a prolonged half-life compared to native FGF21 that is currently being developed for treatment of non-alcoholic steatohepatitis (NASH) and severe hypertriglyceridemia (SHTG).

• In a randomized, placebo-controlled Phase 1b/2a POC study in subjects with NASH, PGZ had a significant liver-related and metabolic benefits.

• In an open-label cohort of this POC study that included subjects with biopsy-confirmed NASH (NAS ≥4, fibrosis stage F2 or F3; N=20), PGZ 27mg for 20 weeks led to clinically meaningful histological improvement, as well as significant liver-related (MRI-PDFF, ALT, multiple fibrosis-related non-invasive tests) and cardiometabolic benefits, with favorable safety and tolerability.

• Intra-reader and inter-reader variability in liver biopsy reads is increasingly recognized as a major challenge to drug development in NASH.

• Assessment of NASH trial biopsy slides by different pathologists (or by the same pathologist at different timepoints) may affect subject eligibility and evaluation of the proportion of subjects who have met histological endpoints.
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Loomba et al.