Aramchol in patients with nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase 2b trial
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 steatohepa...
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| Veröffentlicht in: | Nature Medicine 2021-10, Vol.27 (10), p.1825-1835 |
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| creator | Ratziu, V. de Guevara, L. Safadi, R. Poordad, F. Fuster, F. Flores-Figueroa, J. Arrese, M. Fracanzani, Anna L. Ben Bashat, D. Lackner, K. Gorfine, T. Kadosh, S. Oren, R. Halperin, M. Hayardeny, L. Loomba, R. Friedman, S. Sanyal, Arun J. |
| description | 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 |
| doi_str_mv | 10.1038/s41591-021-01495-3 |
| format | Article |
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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.
In a phase 2b study, inhibition of hepatic stearoyl-CoA desaturase in patients with nonalcoholic steatohepatitis was safe and tolerated; although reductions in liver fat were not significant, changes in liver enzymes and histology were observed.</description><identifier>ISSN: 1078-8956</identifier><identifier>EISSN: 1546-170X</identifier><identifier>EISSN: 1744-7933</identifier><identifier>DOI: 10.1038/s41591-021-01495-3</identifier><identifier>PMID: 34621052</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>692/699/1503/1607/2750 ; 692/699/1503/1607/2751 ; Adverse events ; Alanine ; Alanine Transaminase ; Biomedical and Life Sciences ; Biomedicine ; Biopsy ; Cancer Research ; Cardiology and cardiovascular system ; Care and treatment ; Cholic acid ; Cholic Acids ; Cholic Acids - administration & dosage ; Cholic Acids - adverse effects ; Cirrhosis ; Clinical trials ; Confidence intervals ; Desaturase ; Diagnosis ; Double-Blind Method ; Double-blind studies ; Eicosanoic acid ; Endocrinology and metabolism ; Enzymes ; Fatty liver ; Female ; Fibrosis ; Hepatocellular carcinoma ; Histology ; Human health and pathology ; Humans ; Infectious Diseases ; Insulin ; Insulin resistance ; Life Sciences ; Liver ; Liver - drug effects ; Liver - metabolism ; Liver - pathology ; Liver cancer ; Liver cirrhosis ; Liver diseases ; Magnetic Resonance Spectroscopy ; Male ; Measurement ; Metabolic Diseases ; Middle Aged ; Molecular Medicine ; Neurosciences ; Non-alcoholic Fatty Liver Disease ; Non-alcoholic Fatty Liver Disease - drug therapy ; Non-alcoholic Fatty Liver Disease - genetics ; Non-alcoholic Fatty Liver Disease - pathology ; Nuclear magnetic resonance spectroscopy ; Patients ; Placebos ; Risk factors ; Statistical analysis ; Stearoyl-CoA Desaturase ; Stearoyl-CoA Desaturase - genetics ; Steatosis ; Testing ; Triglycerides ; Triglycerides - metabolism</subject><ispartof>Nature Medicine, 2021-10, Vol.27 (10), p.1825-1835</ispartof><rights>The Author(s), under exclusive licence to Springer Nature America, Inc. 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer Nature America, Inc.</rights><rights>COPYRIGHT 2021 Nature Publishing Group</rights><rights>The Author(s), under exclusive licence to Springer Nature America, Inc. 2021.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c512t-c4654df88287c9c72f3ad5ae9e77b1f22f8536a109c6fd92419dddd352763f513</citedby><cites>FETCH-LOGICAL-c512t-c4654df88287c9c72f3ad5ae9e77b1f22f8536a109c6fd92419dddd352763f513</cites><orcidid>0000-0002-6865-3791 ; 0000-0001-8682-5748 ; 0000-0003-1790-5124 ; 0000-0002-4845-9991 ; 0000-0003-1178-6195</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41591-021-01495-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41591-021-01495-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34621052$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.sorbonne-universite.fr/hal-03520782$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Ratziu, V.</creatorcontrib><creatorcontrib>de Guevara, L.</creatorcontrib><creatorcontrib>Safadi, R.</creatorcontrib><creatorcontrib>Poordad, F.</creatorcontrib><creatorcontrib>Fuster, F.</creatorcontrib><creatorcontrib>Flores-Figueroa, J.</creatorcontrib><creatorcontrib>Arrese, M.</creatorcontrib><creatorcontrib>Fracanzani, Anna L.</creatorcontrib><creatorcontrib>Ben Bashat, D.</creatorcontrib><creatorcontrib>Lackner, K.</creatorcontrib><creatorcontrib>Gorfine, T.</creatorcontrib><creatorcontrib>Kadosh, S.</creatorcontrib><creatorcontrib>Oren, R.</creatorcontrib><creatorcontrib>Halperin, M.</creatorcontrib><creatorcontrib>Hayardeny, L.</creatorcontrib><creatorcontrib>Loomba, R.</creatorcontrib><creatorcontrib>Friedman, S.</creatorcontrib><creatorcontrib>Sanyal, Arun J.</creatorcontrib><creatorcontrib>ARREST investigator study group</creatorcontrib><creatorcontrib>the ARREST investigator study group</creatorcontrib><title>Aramchol in patients with nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase 2b trial</title><title>Nature Medicine</title><addtitle>Nat Med</addtitle><addtitle>Nat Med</addtitle><description>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.
In a phase 2b study, inhibition of hepatic stearoyl-CoA desaturase in patients with nonalcoholic steatohepatitis was safe and tolerated; although reductions in liver fat were not significant, changes in liver enzymes and histology were observed.</description><subject>692/699/1503/1607/2750</subject><subject>692/699/1503/1607/2751</subject><subject>Adverse events</subject><subject>Alanine</subject><subject>Alanine Transaminase</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biopsy</subject><subject>Cancer Research</subject><subject>Cardiology and cardiovascular system</subject><subject>Care and treatment</subject><subject>Cholic acid</subject><subject>Cholic Acids</subject><subject>Cholic Acids - administration & dosage</subject><subject>Cholic Acids - adverse effects</subject><subject>Cirrhosis</subject><subject>Clinical trials</subject><subject>Confidence intervals</subject><subject>Desaturase</subject><subject>Diagnosis</subject><subject>Double-Blind Method</subject><subject>Double-blind studies</subject><subject>Eicosanoic acid</subject><subject>Endocrinology and metabolism</subject><subject>Enzymes</subject><subject>Fatty liver</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Hepatocellular carcinoma</subject><subject>Histology</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Infectious Diseases</subject><subject>Insulin</subject><subject>Insulin resistance</subject><subject>Life Sciences</subject><subject>Liver</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver cancer</subject><subject>Liver cirrhosis</subject><subject>Liver diseases</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Male</subject><subject>Measurement</subject><subject>Metabolic Diseases</subject><subject>Middle Aged</subject><subject>Molecular Medicine</subject><subject>Neurosciences</subject><subject>Non-alcoholic Fatty Liver Disease</subject><subject>Non-alcoholic Fatty Liver Disease - drug therapy</subject><subject>Non-alcoholic Fatty Liver Disease - genetics</subject><subject>Non-alcoholic Fatty Liver Disease - pathology</subject><subject>Nuclear magnetic resonance spectroscopy</subject><subject>Patients</subject><subject>Placebos</subject><subject>Risk factors</subject><subject>Statistical analysis</subject><subject>Stearoyl-CoA Desaturase</subject><subject>Stearoyl-CoA Desaturase - genetics</subject><subject>Steatosis</subject><subject>Testing</subject><subject>Triglycerides</subject><subject>Triglycerides - metabolism</subject><issn>1078-8956</issn><issn>1546-170X</issn><issn>1744-7933</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kV1rFTEQhhex2Fr9A15IQCgIruZjk9307lDUFg54o-BdmM1muynZZE2ySv315ri11hsDQ2YyzwyTeavqBcFvCWbdu9QQLkmNaTHSSF6zR9UJ4Y2oSYu_Pi4-bru6k1wcV09TusEYM8zlk-qYNYISzOlJte4izHoKDlmPFsjW-JzQD5sn5IMHp0PJWY1SNpDDZA5ItukcAYrghzDbn2Z4g4aw9s7UvbO-RIsDbfpQ6-BzDM6ZAS0TJINoj3K04J5VRyO4ZJ7f3afVlw_vP19c1vtPH68udvtac0JzrRvBm2HsOtq1WuqWjgwGDkaatu3JSOnYcSaAYKnFOEjaEDmUwzhtBRs5YafV663vBE4t0c4Qb1UAqy53e3V4w4UtS6LfD-yrjV1i-LaalNVNWGNZQVKUd0QKQcQD6hqcUdaPIUfQs01a7UQrsZAtpYU6e0BNBlyeUnBrtsGnf0G6gTqGlKIZ76ckWB1EVpvIqoisfousWCl6eTfp2s9muC_5o2oB2AakkvLXJv79yn_a_gLtvLBK</recordid><startdate>20211001</startdate><enddate>20211001</enddate><creator>Ratziu, V.</creator><creator>de Guevara, 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in patients with nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase 2b trial</title><author>Ratziu, V. ; de Guevara, L. ; Safadi, R. ; Poordad, F. ; Fuster, F. ; Flores-Figueroa, J. ; Arrese, M. ; Fracanzani, Anna L. ; Ben Bashat, D. ; Lackner, K. ; Gorfine, T. ; Kadosh, S. ; Oren, R. ; Halperin, M. ; Hayardeny, L. ; Loomba, R. ; Friedman, S. ; Sanyal, Arun J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c512t-c4654df88287c9c72f3ad5ae9e77b1f22f8536a109c6fd92419dddd352763f513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>692/699/1503/1607/2750</topic><topic>692/699/1503/1607/2751</topic><topic>Adverse events</topic><topic>Alanine</topic><topic>Alanine Transaminase</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biopsy</topic><topic>Cancer Research</topic><topic>Cardiology and cardiovascular system</topic><topic>Care and treatment</topic><topic>Cholic acid</topic><topic>Cholic Acids</topic><topic>Cholic Acids - administration & dosage</topic><topic>Cholic Acids - adverse effects</topic><topic>Cirrhosis</topic><topic>Clinical trials</topic><topic>Confidence intervals</topic><topic>Desaturase</topic><topic>Diagnosis</topic><topic>Double-Blind Method</topic><topic>Double-blind studies</topic><topic>Eicosanoic acid</topic><topic>Endocrinology and metabolism</topic><topic>Enzymes</topic><topic>Fatty liver</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Hepatocellular carcinoma</topic><topic>Histology</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Infectious Diseases</topic><topic>Insulin</topic><topic>Insulin resistance</topic><topic>Life Sciences</topic><topic>Liver</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver cancer</topic><topic>Liver cirrhosis</topic><topic>Liver diseases</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Male</topic><topic>Measurement</topic><topic>Metabolic Diseases</topic><topic>Middle Aged</topic><topic>Molecular Medicine</topic><topic>Neurosciences</topic><topic>Non-alcoholic Fatty Liver Disease</topic><topic>Non-alcoholic Fatty Liver Disease - drug therapy</topic><topic>Non-alcoholic Fatty Liver Disease - genetics</topic><topic>Non-alcoholic Fatty Liver Disease - pathology</topic><topic>Nuclear magnetic resonance spectroscopy</topic><topic>Patients</topic><topic>Placebos</topic><topic>Risk factors</topic><topic>Statistical analysis</topic><topic>Stearoyl-CoA Desaturase</topic><topic>Stearoyl-CoA Desaturase - genetics</topic><topic>Steatosis</topic><topic>Testing</topic><topic>Triglycerides</topic><topic>Triglycerides - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ratziu, V.</creatorcontrib><creatorcontrib>de Guevara, 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Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Nature Medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ratziu, V.</au><au>de Guevara, L.</au><au>Safadi, R.</au><au>Poordad, F.</au><au>Fuster, F.</au><au>Flores-Figueroa, J.</au><au>Arrese, M.</au><au>Fracanzani, Anna L.</au><au>Ben Bashat, D.</au><au>Lackner, K.</au><au>Gorfine, T.</au><au>Kadosh, S.</au><au>Oren, R.</au><au>Halperin, M.</au><au>Hayardeny, L.</au><au>Loomba, R.</au><au>Friedman, S.</au><au>Sanyal, Arun J.</au><aucorp>ARREST investigator study group</aucorp><aucorp>the ARREST investigator study group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aramchol in patients with nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase 2b trial</atitle><jtitle>Nature Medicine</jtitle><stitle>Nat Med</stitle><addtitle>Nat Med</addtitle><date>2021-10-01</date><risdate>2021</risdate><volume>27</volume><issue>10</issue><spage>1825</spage><epage>1835</epage><pages>1825-1835</pages><issn>1078-8956</issn><eissn>1546-170X</eissn><eissn>1744-7933</eissn><abstract>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.
In a phase 2b study, inhibition of hepatic stearoyl-CoA desaturase in patients with nonalcoholic steatohepatitis was safe and tolerated; although reductions in liver fat were not significant, changes in liver enzymes and histology were observed.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>34621052</pmid><doi>10.1038/s41591-021-01495-3</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-6865-3791</orcidid><orcidid>https://orcid.org/0000-0001-8682-5748</orcidid><orcidid>https://orcid.org/0000-0003-1790-5124</orcidid><orcidid>https://orcid.org/0000-0002-4845-9991</orcidid><orcidid>https://orcid.org/0000-0003-1178-6195</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-8956 |
| ispartof | Nature Medicine, 2021-10, Vol.27 (10), p.1825-1835 |
| issn | 1078-8956 1546-170X 1744-7933 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_03520782v1 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature; EZB-FREE-00999 freely available EZB journals |
| subjects | 692/699/1503/1607/2750 692/699/1503/1607/2751 Adverse events Alanine Alanine Transaminase Biomedical and Life Sciences Biomedicine Biopsy Cancer Research Cardiology and cardiovascular system Care and treatment Cholic acid Cholic Acids Cholic Acids - administration & dosage Cholic Acids - adverse effects Cirrhosis Clinical trials Confidence intervals Desaturase Diagnosis Double-Blind Method Double-blind studies Eicosanoic acid Endocrinology and metabolism Enzymes Fatty liver Female Fibrosis Hepatocellular carcinoma Histology Human health and pathology Humans Infectious Diseases Insulin Insulin resistance Life Sciences Liver Liver - drug effects Liver - metabolism Liver - pathology Liver cancer Liver cirrhosis Liver diseases Magnetic Resonance Spectroscopy Male Measurement Metabolic Diseases Middle Aged Molecular Medicine Neurosciences Non-alcoholic Fatty Liver Disease Non-alcoholic Fatty Liver Disease - drug therapy Non-alcoholic Fatty Liver Disease - genetics Non-alcoholic Fatty Liver Disease - pathology Nuclear magnetic resonance spectroscopy Patients Placebos Risk factors Statistical analysis Stearoyl-CoA Desaturase Stearoyl-CoA Desaturase - genetics Steatosis Testing Triglycerides Triglycerides - metabolism |
| title | Aramchol in patients with nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase 2b trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T19%3A44%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Aramchol%20in%20patients%20with%20nonalcoholic%20steatohepatitis:%20a%20randomized,%20double-blind,%20placebo-controlled%20phase%202b%20trial&rft.jtitle=Nature%20Medicine&rft.au=Ratziu,%20V.&rft.aucorp=ARREST%20investigator%20study%20group&rft.date=2021-10-01&rft.volume=27&rft.issue=10&rft.spage=1825&rft.epage=1835&rft.pages=1825-1835&rft.issn=1078-8956&rft.eissn=1546-170X&rft_id=info:doi/10.1038/s41591-021-01495-3&rft_dat=%3Cgale_hal_p%3EA679069722%3C/gale_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2581966161&rft_id=info:pmid/34621052&rft_galeid=A679069722&rfr_iscdi=true |