Safety and efficacy profile of S-005151 (Redasemtide), in patients with chronic liver diseases: phase 2 trial

BACKGROUND AND AIMS: Cirrhosis is a disease of impaired liver function and fibrosis caused by long-term liver damage. However, to date, no drugs have been approved to improve liver fibrosis. We report the results of a phase 2 study of S-005151 (generic name: Redasemtide), a partial peptide of High-Mobility Group Box 1 (HMGB1), in patients with chronic liver disease. APPROACH AND RESULTS: This single-center, non-randomized, single-arm, open-label study was performed in Japan in patients with chronic liver disease (cohort A: 5 patients, cohort B: 5 patients) caused by HCV, HBV, MASH, or alcohol, with MR elastography of ≥ 4 kPa and Child-Pugh score up to 7 points. The primary endpoint was safety; secondary endpoints were efficacy against liver injury, function, and fibrosis. One adverse event (dysphonia) was observed in cohort A and one (fever) in cohort B, both of which were mild drug-related adverse events. S-005151 was well-tolerated. Regarding efficacy, there was a trend toward improvement post-treatment, with a decrease in transaminase and improvement in tissue inflammation scores in some cases; however, there was no significant improvement in hepatic dysfunction. Regarding liver fibrosis, there was a rapid and stable decrease in serum type IV collagen 7S levels, improvement in MR elastography findings, and an increase in platelet counts in some cases; 5 of 10 patients showed a trend toward improvement in liver fibrosis. CONCLUSIONS: S-005151 is well-tolerated in patients with chronic liver disease and may have therapeutic effects, in reducing liver damage and improving liver fibrosis. TRIAL REGISTRATION: jRCT, jRCT 2031200232, Registered 4 December 2020 (https://jrct.mhlw.go.jp/latest-detail/jRCT2031200232).