While no regimen led to a statistically significant increase in the proportion of patients who achieved the primary efficacy endpoint of a ≥1-stage improvement in fibrosis without worsening of NASH, statistically significant improvements in multiple response measures of fibrosis and liver function were observed in patients treated with a combination of the acetyl-CoA carboxylase inhibitor firsocostat and the selective, nonsteroidal farnesoid X receptor agonist cilofexor, compared with placebo in patients with advanced fibrosis.
The Phase 2 ATLAS study is a randomised, double-blind, placebo-controlled study that evaluated the safety and efficacy of monotherapy and dual combination regimens of cilofexor 30 mg, firsocostat 20 mg and selonsertib 18 mg in patients with advanced fibrosis (F3-F4) due to NASH.
The selonsertib monotherapy treatment group was discontinued following termination of the previously reported STELLAR trials of selonsertib.
NASH resolution without worsening of fibrosis was uncommon in all treatment groups, including no placebo-treated patients and 4.5% of those treated with firsocostat and cilofexor (p=0.35).
Statistically significant improvements in multiple secondary endpoints were observed in patients treated with firsocostat and cilofexor compared with placebo, including a ≥2-point reduction in the NAFLD Activity Score and ≥1-point reductions in steatosis, hepatocellular ballooning and lobular inflammation.
Statistically significant improvements in noninvasive tests of fibrosis, liver injury and function, including ALT, AST, bilirubin and ELF score, were also observed in patients treated with this regimen compared with placebo.
Firsocostat, cilofexor and selonsertib, as monotherapies and dual combination regimens, were generally well tolerated.
The most common adverse events in patients treated with the combination of firsocostat and cilofexor were mild to moderate pruritus (28.2 % vs 15.4 % with placebo; no discontinuations), headache, diarrhea and nausea.
In patients treated with firsocostat and cilofexor, changes in lipid parameters were similar to those observed previously; 3.9 % of patients experienced asymptomatic Grade 3 triglyceride elevations (>500 and
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