NGM Biopharmaceuticals has reported that aldafermin failed to meet the primary endpoint of the Phase IIb ALPINE 2/3 clinical trial in non-alcoholic steatohepatitis (NASH) patients with stage 2 or 3 liver fibrosis (F2/F3).
An analogue of the human hormone FGF19, aldafermin is being developed to treat various liver and metabolic diseases. To date, it has been tested in more than 650 healthy participants and patients.
The multi-centre, double-blind, randomised, placebo-controlled ALPINE 2/3 trial assessed the safety, efficacy and tolerability of 0.3mg, 1mg and 3mg doses of once-daily subcutaneous aldafermin, when compared to placebo, over 24 weeks.
Involving 171 patients, the trial examined a dose-response of fibrosis improvement >1 stage without disease worsening at week 24 as the primary endpoint.
Secondary endpoints were disease resolution, fibrosis improvement, NASH resolution, and relative changes in LFC, ALT, AST and fibrosis biomarkers at week 24.
In addition, safety and non-invasive measures were assessed at week 30 after six weeks off therapy.
Though the trial failed to meet the primary endpoint, it showed statistical significance on some secondary endpoints, including NASH resolution with the 3mg dose, and various non-invasive NASH measures.
The overall safety profile of the drug in this trial was found to be consistent with previous data and comparable to that of placebo.
NGM Biopharmaceuticals CEO David Woodhouse said: “These results are certainly disappointing, particularly given the dire unmet need in this patient population. The lack of significant fibrosis improvement was unexpected given the consistency of histology findings previously seen with aldafermin in our adaptive four-cohort Phase II study.
“However, in line with the data from that study, ALPINE 2/3 achieved statistical significance on multiple non-invasive measures of NASH at the two higher doses.”
The company will continue patient recruitment in its ongoing Phase IIb ALPINE 4 study of aldafermin in F4 NASH patients with compensated cirrhosis.
Meanwhile, resources previously reserved for a Phase III F2/F3 NASH development programme will now be directed towards the company’s ophthalmology and oncology programmes.
In February 2020, NGM reported positive data from the fourth cohort of a Phase II trial of aldafermin in NASH patients.