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Lancet. 2018 Mar 24;391(10126):1174-1185. doi: 10.1016/S0140-6736(18)30474-4. Epub 2018 Mar 5.

NGM282 for treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

Author information

Radcliffe Department of Medicine, University of Oxford, Oxford, UK. Electronic address:
Division of Gastroenterology and Hepatology, Northwestern University, Chicago, IL, USA.
Duke University, Durham, NC, USA.
Clinical Research and Education, Texas Digestive Disease Consultants, Dallas, TX, USA.
Division of Gastroenterology and Hepatology, Brooke Army Medical Center, San Antonio, TX, USA.
Gastroenterology Consultants of San Antonio, Live Oak, TX, USA.
Hepatology, South Denver Gastroenterology, Englewood, CO, USA.
Department of Radiology, Duke University Medical Center, Durham, NC, USA.
Summit Analytical, Denver, CO, USA.
NGM Biopharmaceuticals, Inc, San Francisco, CA, USA.
Non-Alcoholic Fatty Liver Disease Research Center, Division of Gastroenterology and Epidemiology, University of California San Diego, San Diego, CA, USA.

Erratum in



Non-alcoholic steatohepatitis is a chronic liver disease characterised by the presence of hepatic steatosis, inflammation, and hepatocellular injury, for which no Food and Drug Administration (FDA)-approved treatment exists. FGF19 is a hormone that regulates bile acid synthesis and glucose homoeostasis. We aimed to assess the safety and efficacy of NGM282, an engineered FGF19 analogue, for the treatment of non-alcoholic steatohepatitis.


In this randomised, double-blind, placebo-controlled, phase 2 study, we recruited patients aged 18-75 years with biopsy-confirmed non-alcoholic steatohepatitis as defined by the non-alcoholic steatohepatitis clinical research network histological scoring system, from hospitals and gastroenterology and liver clinics in Australia and the USA. Key eligibility criteria included a non-alcoholic fatty liver disease activity score of 4 or higher, stage 1-3 fibrosis, and at least 8% liver fat content. Patients were randomly assigned (1:1:1) via a web-based system and stratified by diabetic status to receive either 3 mg or 6 mg subcutaneous NGM282 or placebo. The primary endpoint was the absolute change from baseline to week 12 in liver fat content. Responders were patients who achieved a 5% or larger reduction in absolute liver fat content as measured by MRI-proton density fat fraction. Efficacy analysis was by intention to treat. This trial is registered with, number NCT02443116.


Between July 14, 2015, and Aug 30, 2016, 166 patients were screened across 18 sites in Australia and the USA. 82 patients were randomly assigned to receive 3 mg NGM282 (n=27), 6 mg NGM282 (n=28), or placebo (n=27). At 12 weeks, 20 (74%) patients in the 3 mg dose group and 22 (79%) in the 6 mg dose group achieved at least a 5% reduction in absolute liver fat content from baseline (relative risk 10·0 [95% CI 2·6-38·7] vs 11·4 [3·0-43·8], respectively; p<0·0001 for both comparisons) versus two (7%) in the placebo group. Overall, 76 (93%) of 82 patients experienced at least one adverse event, most of which were grade 1 (55 [67%]), and only five (6%) were grade 3 or worse. The most commonly (≥10%) reported adverse events were injection site reactions (28 [34%]), diarrhoea (27 [33%]), abdominal pain (15 [18%]), and nausea (14 [17%]). These adverse events were reported more frequently in the NGM282 groups compared with the placebo group. No life-threatening events or patient deaths occurred during the study.


NGM282 produced rapid and significant reductions in liver fat content with an acceptable safety profile in patients with non-alcoholic steatohepatitis. Further study of NGM282 is warranted in this patient population.


NGM Biopharmaceuticals.

[Indexed for MEDLINE]

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