Aldafermin Shows Promise in Reducing Liver Fibrosis in Compensated NASH Cirrhosis

A recent phase 2b trial has revealed promising results for aldafermin, an engineered analog of the human hormone FGF19, in treating compensated nonalcoholic steatohepatitis (NASH) cirrhosis. The study, conducted as a multicenter, double-blind, placebo-controlled trial, aimed to assess the efficacy and safety of aldafermin in 160 patients with compensated NASH cirrhosis. This study was published in the Hepatology journal by Rinella and colleagues.

Patients were randomized to receive aldafermin at doses of 0.3 mg, 1 mg, 3 mg, or a placebo over a 48-week period. The primary endpoint measured was the change in ELF (Enhanced Liver Fibrosis) score from baseline to week 48. The study revealed that the 3 mg dosage of aldafermin resulted in a significant reduction in ELF compared to the placebo group. Specifically, the least squares mean difference in the change in ELF was -0.5 between the 3 mg group and the placebo group (p=0.0003).

Furthermore, a notable percentage of patients in the aldafermin groups achieved fibrosis improvement of ≥1-stage: 21% in the 1 mg group and 23% in the 3 mg group, compared to 15% in the placebo group. Additionally, improvements were observed in liver enzymes (ALT, AST), Pro-C3 (a marker of liver fibrosis), and liver stiffness in favor of the aldafermin groups.

Among the observed adverse events, diarrhea was the most frequent, occurring in 26% and 40% of patients in the 1 mg and 3 mg aldafermin groups, respectively, compared to 18% in the placebo group. However, a low percentage of patients discontinued treatment due to treatment-related adverse events (0%, 2%, and 9% in the placebo, 1 mg, and 3 mg groups, respectively).

The findings suggest that aldafermin, particularly at the 3 mg dosage, demonstrates significant promise in reducing liver fibrosis in patients with compensated NASH cirrhosis. The treatment also showed improvements in liver enzymes and stiffness. However, diarrhea emerged as a common adverse event, but discontinuation due to adverse events was relatively low.

Researchers concluded that these results provide optimism for the potential of aldafermin as a therapeutic option for compensated NASH cirrhosis. Further research and larger-scale trials may better elucidate its efficacy and safety profile in this patient population.

Reference:

Rinella, M. E., Lieu, H. D., Kowdley, K. V., Goodman, Z. D., Alkhouri, N., Lawitz, E., Ratziu, V., Abdelmalek, M. F., Wong, V. W.-S., Younes, Z. H., Sheikh, A. M., Brannan, D., Freilich, B., Membreno, F., Sinclair, M., Melchor-Khan, L., Sanyal, A. J., Ling, L., & Harrison, S. A. A randomized, double-blind, placebo-controlled trial of Aldafermin in patients with nonalcoholic steatohepatitis and compensated cirrhosis. Hepatology (Baltimore, Md.),2023. https://doi.org/10.1097/hep.0000000000000607