Aramchol in patients with nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase 2b trial

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dc.contributor.authorRatziu, V.
dc.contributor.authorde Guevara, L.
dc.contributor.authorSafadi, R.
dc.contributor.authorPoordad, F.
dc.contributor.authorFuster, F.
dc.contributor.authorFlores-Figueroa, J.
dc.contributor.authorArrese, M.
dc.contributor.authorFracanzani, Anna L.
dc.contributor.authorBen Bashat, D.
dc.contributor.authorLackner, K.
dc.contributor.authorGorfine, T.
dc.contributor.authorKadosh, S.
dc.contributor.authorOren, R.
dc.contributor.authorHalperin, M.
dc.contributor.authorHayardeny, L.
dc.contributor.authorLoomba, R.
dc.contributor.authorFriedman, S.
dc.contributor.authorSanyal, Arun J.
dc.date.accessioned2025-01-20T22:07:22Z
dc.date.available2025-01-20T22:07:22Z
dc.date.issued2021
dc.description.abstractY Nonalcoholic steatohepatitis (NASH), a chronic liver disease without an approved therapy, is associated with lipotoxicity and insulin resistance and is a major cause of cirrhosis and hepatocellular carcinoma. Aramchol, a partial inhibitor of hepatic stearoyl-CoA desaturase (SCD1) improved steatohepatitis and fibrosis in rodents and reduced steatosis in an early clinical trial. ARREST, a 52-week, double-blind, placebo-controlled, phase 2b trial randomized 247 patients with NASH (n = 101, n = 98 and n = 48 in the Aramchol 400 mg, 600 mg and placebo arms, respectively; NCT02279524). The primary end point was a decrease in hepatic triglycerides by magnetic resonance spectroscopy at 52 weeks with a dose of 600 mg of Aramchol. Key secondary end points included liver histology and alanine aminotransferase (ALT). Aramchol 600 mg produced a placebo-corrected decrease in liver triglycerides without meeting the prespecified significance (-3.1, 95% confidence interval (CI) -6.4 to 0.2, P = 0.066), precluding further formal statistical analysis. NASH resolution without worsening fibrosis was achieved in 16.7% (13 out of 78) of Aramchol 600 mg versus 5% (2 out of 40) of the placebo arm (odds ratio (OR) = 4.74, 95% CI = 0.99 to 22.7) and fibrosis improvement by >= 1 stage without worsening NASH in 29.5% versus 17.5% (OR = 1.88, 95% CI = 0.7 to 5.0), respectively. The placebo-corrected decrease in ALT for 600 mg was -29.1 IU l(-1) (95% CI = -41.6 to -16.5). Early termination due to adverse events (AEs) was <5%, and Aramchol 600 and 400 mg were safe, well tolerated and without imbalance in serious or severe AEs between arms. Although the primary end point of a reduction in liver fat did not meet the prespecified significance level with Aramchol 600 mg, the observed safety and changes in liver histology and enzymes provide a rationale for SCD1 modulation as a promising therapy for NASH and fibrosis and are being evaluated in an ongoing phase 3 program.
dc.description.funderGalmed Pharmaceuticals
dc.fuente.origenWOS
dc.identifier.doi10.1038/s41591-021-01495-3
dc.identifier.eissn1546-170X
dc.identifier.issn1078-8956
dc.identifier.urihttps://doi.org/10.1038/s41591-021-01495-3
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94236
dc.identifier.wosidWOS:000704942800001
dc.issue.numero10
dc.language.isoen
dc.pagina.final+
dc.pagina.inicio1825
dc.revistaNature medicine
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleAramchol in patients with nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase 2b trial
dc.typeartículo
dc.volumen27
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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