Aldafermin produces fibrosis regression in NASH
Patients with nonalcoholic steatohepatitis with advanced fibrosis experienced fibrosis regression after treatment with aldafermin, according to research presented at The Liver Meeting Digital Experience.
In his presentation, Guy W. Neff, MD, from Covenant Research, said aldafermin (NGM Biopharmaceuticals), and FGF19 analogue, has previously been tested in three patient cohorts for a treatment period of 12 weeks in various doses. Neff’s presentation comprised a subgroup analysis of the fourth study cohort, with evaluated 1 mg of the drug for 24 weeks compared with placebo. Specifically, Neff and colleagues focused on patients with NASH fibrosis stage 2 (n = 44) vs. those with NASH fibrosis stage 3 (n = 34) at baseline.
Researchers included patients with biopsy-confirmed NASH, an absolute liver fat content of at least 8% and an ALT of at least 19 IU/L in women and at least 30 IU/L in men.
The primary endpoint of the study was change in baseline in absolute liver fat content as measured by MRI-PDFF at week 24. They also explored the impact on liver histology, ALT, AST and biomarkers of fibrosis at week 24.
In patients with stage 2 fibrosis, 74% of patients who received aldafermin achieved at least 5% in absolute liver fat content compared with 31% of those who received placebo (change = 43%). In patients with stage 3 fibrosis, 61% achieved the primary endpoint, and a smaller percentage have a placebo response (12%; change = 49%).
Among patients who achieved at least 30% relative reduction in liver fat content, aldafermin produced a greater placebo-subtract, anti-fibrotic response in patients with stage 3 fibrosis (change = 46%) compared with those with stage 2 (change = 5%).
Patients who received the drug also experienced reduction in ALT, AST and PRO-C3 regardless of baseline fibrosis stage.
Neff said their findings support further studies of aldafermin in patients with NASH and advanced fibrosis.
“These patients, as we know, are at higher risk for professing to cirrhosis, liver failure and cancer,” Neff said. “Robust efficacy in this vulnerable population shows the attractiveness of aldafermin’s profile as potential treatment for NASH.”