In a phase 2b, placebo-controlled, randomized, multicentre, double-blind trial (HARMONY), Efruxifermin, administered for 24 weeks, was associated with better resolution of liver fibrosis and non-alcoholic steatohepatitis (NASH) in adults battling NASH and moderate (F2) or severe (F3) fibrosis. Efruxifermin maintained acceptable tolerability throughout the trial period. Stephen A Harrison et al. sought to explore the safety and efficiency of the Efruxifermin treatment in fibrosis and NASH.

Those diagnosed with NASH confirmed by biopsy, characterized by a non-alcoholic fatty liver disease activity score (NAS) of 4 or greater and scores of 1 or greater in each steatosis, lobular inflammation with histological stage F2 or F3 fibrosis, and ballooning were randomized (1:1:1) through interactive response system to get either Efruxifermin or placebo (50 mg or 28 mg) via subcutaneous route once a week. Throughout the study, patients, investigators, pathologists, site staff, and the sponsor remained unaware of group assignments.

As determined by evaluation of baseline and week 24 biopsies (liver biopsy analysis set [LBAS]), the major outcome focused on the percentage of subjects showing enhancements in fibrosis of minimum 1 stage with no worsening of NASH. Sensitivity analysis was utilized to assess outcome in the full analysis set, where subjects with missing biopsies were treated as non-responders.

A total of 747 individuals were evaluated for eligibility, and 128 participants (with a mean age of 54.7 years [standard deviation 10.4], comprising 62%  females [n= 79] and 38% males [n= 49], with 92% [n= 118] being white and 41% [n= 56] Hispanic or Latino) were recruited and randomized to one of three groups: placebo (n= 43), 28 mg Efruxifermin (n= 42; 2 randomized subjects were not dosed because of an administrative error), or 50 mg Efruxifermin (n= 43). Among the LBAS group (n= 113), 8 (20%) out of 41 volunteers in the placebo group demonstrated a betterment in fibrosis by a minimum of 1 stage with no worsening of NASH by week 24.

In comparison, 15 (39%) out of 38 individuals in the 28 mg Efruxifermin group (risk ratio [RR] 2.3) and 14 (41%) out of 34 subjects in the 50 mg Efruxifermin group (RR 2.2) met the major outcome. According to the full analysis set (n= 128), 8 (19%) of 43 people in the placebo group achieved the outcome, while 15 (36%) of 42 in 28 mg Efruxifermin group (RR 2.2) and 14 (33%) of 43 in 50 mg Efruxifermin group (RR 1.9) fulfilled the criteria.

The primary Efruxifermin-related side effects were diarrhea (occurring in 16 [40%] of 40 patients in the 28 mg Efruxifermin group and 17 [40%] of 43 patients in the 50 mg Efruxifermin group, compared to 8 [19%] of 43 people in placebo group; all the events with the exception of one were classified as grade 1–2) and nausea (reported in 11 [28%] subjects in 28 mg Efruxifermin group and 18 [42%] volunteers in 50 mg Efruxifermin group, as opposed to ten [23%] individuals in placebo group; all grade 1–2).

Five volunteers (two in the 28 mg arm and three in the 50 mg arm) ceased participation because of side effects. Deleterious side effects were witnessed in four individuals in the 50 mg arm, with one being characterized as drug-related (ulcerative esophagitis in a subject having a history of gastroesophageal reflux disease). No fatalities were reported. Over a 24-week period, Efruxifermin demonstrated efficacy in enhancing liver fibrosis and resolving NASH in people with F2 or F3 fibrosis. The treatment exhibited acceptable tolerability, thereby endorsing its suitability for continued evaluation in phase 3 trials.