Pemvidutide linked to ‘rapid and potent’ reduction in liver fat in MASLD at 12 weeks
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Key takeaways:
- Pemvidutide-treated patients achieved relative reductions in liver fat content of up to 68.5% vs. 4.4% with placebo.
- Improvements in biomarkers of inflammation and body weight also were reported with pemvidutide.
Pemvidutide, a glucagon-like peptide-1/glucagon dual receptor agonist, lowered liver fat content, markers of inflammation and body weight in patients with metabolic dysfunction-associated steatotic liver disease and obesity, research showed.
“As there is no GLP-1R expression in the liver, the effects of GLP-1R agonism on liver fat content, believed to be the principal driver of MASH and liver fibrosis, are passive and follow the general reduction in adiposity associated with weight loss,” John J. Suschak III, PhD, senior director of translational science at Altimmune, and colleagues wrote in the Journal of Hepatology.
The researchers noted that in a previous phase 1 clinical trial, pemvidutide-treated patients exhibited statistically significant reductions in body weight, BMI and serum lipids, as well as a reduction in liver fat content among those with steatosis.
In this multicenter, double-blind study, Suschak and colleagues assessed the effect of pemvidutide on 94 adult patients with MASLD who were overweight or obese. The researchers grouped participants according to presence or absence of type 2 diabetes and randomly assigned them 1:1:1:1 to once-weekly subcutaneous pemvidutide 1.2 mg, 1.8 mg or 2.4 mg or placebo for 12 weeks.
Baseline characteristics were similar across treatment groups, with mean age ranging from 47.9 years to 50.3 years. Most participants were women and 29% of patients had type 2 diabetes. Median BMI and liver fat content were 36.2 kg/m2 and 20.6%, respectively.
The researchers noted they did not use dose titration in patients administered pemvidutide 1.2 mg or 1.8 mg; however, a 4-week titration was used for those who received 2.4 mg (0.6 mg at week 1, 1.2 mg at week 2 and 1.8 mg at weeks 3 and 4) to achieve the 2.4 mg target dose for 8 weeks.
The primary outcomes were absolute and relative reductions in liver fat content from baseline, while secondary endpoints included absolute changes in serum alanine transaminase and percent change in body weight.
According to results, the pemvidutide groups reached statistically significant reductions in liver fat content at week 12 vs. the placebo group, with relative reductions from baseline of 46.6% (95% CI, –63.7 to –29.6) in the 1.2 mg group, 68.5% (95% CI, –84.4 to –52.2) in the 1.8 mg group and 57.1% (95% CI, –76.1 to –38.1) in 2.4 mg group vs. 4.4% (95% CI, –20.2 to 11.3) with placebo. Absolute reductions were 8.9% (95% CI, –12.4 to –5.4), 14.7% (95% CI, –18 to –11.4) and 11.3% (95% CI, –15.3 to –7.4), respectively, vs. 0.2% (95% CI, –3.4 to 3.1).
In addition, the researchers reported that up to 94.4% of patients treated with pemvidutide achieved at least a 30% reduction in liver fat content vs. 4.2% with placebo, and up to 72.2% achieved a 50% reduction or more vs. none with placebo.
Normalization of liver fat was achieved in up to 55.6% of pemvidutide-treated patients and significant improvements also were observed in hepatic inflammation noninvasive biomarkers, including ALT and iron-corrected T1 (cT1). In addition, those who were treated with pemvidutide achieved more significant weight loss — up to 4.3% vs. 0.2% with placebo.
The researchers reported no severe or serious adverse events among those treated with pemvidutide.
“Pemvidutide led to rapid and potent reductions in liver fat content, serum ALT, cT1 and body weight over 12 weeks of dosing,” Suschak and colleagues wrote. “While this was a non-invasive study that was conducted in MASLD, the rapid and significant reductions in steatosis and hepatic inflammation observed in this study may be predictive of improvements in MASH, including its histopathological endpoints and associated comorbidities in late-phase clinical studies.”
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