Oral PXL770 Associated With Only Modest Decrease in Liver Fat Content in NAFLD

Investigators assessed the safety and efficacy of PXL770 in reducing liver fat content in patients with nonalcoholic fatty liver disease.

Oral administration of PXL770 did not significantly reduce liver fat content compared with placebo, but was well tolerated in patients with nonalcoholic fatty liver disease (NAFLD), according to a study in Lancet Gastroenterology and Hepatology.

Investigators assessed the efficacy and safety of PXL770, a novel direct adenosine monophosphate kinase (AMPK) activator, in patients with NAFLD during a randomized, double-blind, placebo-controlled, phase 2a, 12-week study (ClinicalTrials.gov Identifier: NCT03763877). The study was conducted at 15 clinical sites in the United States. Eligible participants were aged 18 to 75 years with liver fat content of at least 10% at baseline, as assessed with magnetic resonance imaging-proton density fat fraction (MRI-PDFF).

The participants were randomly assigned (1:1:1:1) to receive oral PXL770 250 mg once daily, 250 mg twice daily, 500 mg once daily, or matched placebo. The patients were stratified according to type 2 diabetes status and study site. The primary outcome was the relative change in percentage of liver fat content from baseline to week 12.

A total of 121 patients screened from March 29, 2019, to March 13, 2020, were eligible for inclusion; 30 patients received 250-mg PXL770 once daily, 31 received 250-mg PXL770 twice daily, 29 received 500-mg PXL770 once daily, and 31 received placebo. Participants’ mean age was 52.5 (SD, 12.5) years, 65% were women, and 86% were White.

Following exclusion of 1 patient in the 250-mg PXL770 twice daily group, in the modified intention-to-treat population of 120 patients, the placebo-subtracted least-squares mean relative change from baseline in liver fat content at week 12 was 0.1% (95% CI, -15.4 to 15.7; P =.99) in the 250-mg once daily group, -13.1% (95% CI, -28.1 to 1.8; P =.084) in the 250-mg twice daily group, and -13.5% (95% CI, -28.5 to 1.4; P =.076) in the 500-mg once daily group. Statistically significant least-squares mean relative changes in liver fat content occurred at the 250-mg twice daily (P =.033) and 500-mg once daily doses (P =.023).

No life-threatening events or deaths occurred. At least 1 treatment-emergent adverse event (TEAE) was reported in 23 patients in the 250-mg once daily group, 20 patients in the 250-mg twice daily group, 21 patients in the 500-mg once daily group, and 21 patients in the placebo group. Diarrhea was the most frequently reported TEAE in all groups.

Study limitations include the relatively small sample size, the short 12-week treatment period, and lack of adjustment for multiple group comparisons. Additionally, participants were not well representative of populations with higher rates of NAFLD.

“The effects of PXL770 were apparently greater in patients with coexisting type 2 diabetes than in the whole cohort,” stated the researchers. “These results support the further investigation of PXL770 as a possible treatment for type 2 diabetes or for [nonalcoholic steatohepatitis], in particular for the large number of patients with [nonalcoholic steatohepatitis ] and coexisting type 2 diabetes, in whom the severity and progression of disease results in a high unmet medical need,” they concluded.

Disclosure: This study was funded by Poxel. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Cusi K, Alkhouri N, Harrison SA, et al. Efficacy and safety of PXL770, a direct AMP kinase activator, for the treatment of non-alcoholic fatty liver disease (STAMP-NAFLD): a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Gastroenterol Hepatol. 2021;6(11):889-902. doi: 10.1016/S2468-1253(21)00300-9