use of Pegbelfermin (therapeutic protein that impersonates the biological features of fibroblast growth factor-21) therapy can significantly improve the multiple disease biomarkers at week 24 in patients with NASH and stage 3 fibrosis.

FALCON 1, a phase-2b study was performed to study the efficacy of Pegbelfermin (PGBF)in nonalcoholic steatohepatitis (NASH) and stage 3 fibrosis patients.

This post hoc analysis explored the influence of PGBF on NASH-related biomarkers, the link between histological evaluations and noninvasive biomarkers, and concordance between the week twenty-four histologically-determined key outcome response and various biomarkers.

Blood-linked composite fibrosis scores, blood-linked and imaging biomarkers were assessed for NASH people with data from FALCON 1 at the baseline through week twenty-four.  The protein signatures of NASH steatosis, inflammation, ballooning, and fibrosis in blood were evaluated via  SomaSignal tests. The linear mixed-effect models were fit as per biomarker. Correlations and concordance were measured among the blood-based biomarkers, imaging, and histological metrics.

As found, PGBF remarkably enhanced blood-based combined liver fibrosis scores (enhanced liver fibrosis [ELF], fibrosis-4 index [FIB-4], aspartate aminotransferase-to-platelet ratio index [APRI]), biomarkers of fibrogenesis (monomeric ADAMTS-2-released N-terminal type III collagen propeptide [PRO-C3] and crosslinked ADAMTS-2-released N-terminal type III collagen propeptide [PC3X]), adiponectin, cytokeratin 18 (CK-18), liver fat fraction and all the SomaSignal tests at week 24. 

Four key categories, namely: tissue injury, steatosis/metabolism, fibrosis, and biopsy-based metrics were identified as per the correlation analyses between histological and noninvasive evaluations. PGBF had concordant-discordant effects when the key outcome versus the biomarker responses was observed. For measures of liver steatosis and metabolism, the most clear and concordant effects were witnessed. In PGBF arms, a noteworthy link between hepatic fat measured histologically and by imaging was perceived.

PGBF leads to improvement of NASH-linked biomarkers most consistently via improvement of liver steatosis, though there were also improvements in biomarkers of fibrosis and tissue injury/inflammation.

For a better understanding of dynamic changes in disease activity due to the pharmacological therapy of NASH, the results from noninvasive measures plus histologically derived evaluations should be taken into account.