Nonalcoholic steatohepatitis (NASH) is characterized by fatty liver, inflammation and injury, and is associated with an increased risk of liver transplantation and death. NASH affects more than 16 million people in the United States and there are no approved treatments. The purpose of this study was to evaluate the safety and efficacy of aldafermin, a modified analog of fibroblast growth factor 19 (FGF19), an intestinal hormone.
Between May 16, 2019 and September 4, 2020, 786 patients were screened, of whom 171 were randomly assigned to a treatment group and included in the intent-to-treat population: 43 in the 0.3 mg aldafermin group , 42 in the 1·0 mg group, 43 in the 3·0 mg group and 43 in the placebo group. A total of 145 (85%) patients completed treatment. At Week 24, among patients who underwent biopsies at both baseline and Week 24, seven (19%) of 36 patients in the placebo group, 11 (31%) of 36 patients in the 0.3 mg d aldafermin (difference 90% CI 12% [−9 to 33]; p=0 11), five (15%) of 34 patients in the 1 0 mg group (difference −5% [−24 to 13]; p=0 80), and 11 (30%) of 37 patients in the 3 0 mg group (difference 10% [−9 to 30]; p = 0.12) showed improvement in liver fibrosis by at least one stage without worsening of NASH, without reaching predefined significance for dose-response (p = 0.55). Adverse events were mostly mild or moderate in intensity. Diarrhea occurred in six (14%) of 43 patients in the placebo group, three (7%) of 43 patients in the 0.3 mg aldafermin group, five (12%) of 41 patients in the 1.0 mg group and ten (23%) of 43 patients in the 3 0 mg group. The incidences of serious adverse events and discontinuations due to adverse events were similar between the groups.
Aldafermin was generally well tolerated but did not produce a significant dose-response in improving fibrosis by at least one stage without worsening NASH, despite positive effects on a number of endpoints. secondary evaluation. The results of this trial could have implications for the design of future NASH trials.