FGF19 and FGF21: In NASH we trust

Area of Science:

• Endocrinology
• Pharmacology

Background:

• Fibroblast Growth Factor 19 (FGF19) and FGF21 are endocrine factors with significant therapeutic promise.
• Multiple therapeutic assets targeting the FGF receptor (FGFR)/beta-klotho (KLB) pathway are in development.

Purpose of the Study:

• To provide a comprehensive analysis of preclinical and clinical data for FGF19 and FGF21 analogs.
• To offer insights into the mechanism of action, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of clinical assets.

Main Methods:

• Systematic review and detailed analysis of published preclinical (rodent, non-human primate) and clinical data.
• Evaluation of mechanistic insights, PK/PD, and efficacy data from available literature.

Main Results:

• Mechanistic insights were derived from preclinical studies in rodents and non-human primates.
• Pharmacodynamic data from clinical studies were analyzed to understand drug effects.
• Multiple FGF19 and FGF21 analogs are advancing, with some entering Phase 3 clinical trials.

Conclusions:

• The scientific understanding and application of endocrine FGFs have advanced significantly.
• FGF19 and FGF21 analogs represent a rapidly evolving area of therapeutic development, nearing late-stage clinical validation.