Pegozafermin effectively lowers liver fat and blood lipid levels in NASH patients: Lancet

A new study conducted by Rohit Loomba and team showed that Pegozafermin was usually well tolerated and linked to clinically significant decreases in liver fat, liver function tests, and blood lipid levels. The findings of this study were published in The Lancet Gastroenterology and Hepatology.

Since there are currently no approved medications to treat the non-alcoholic steatohepatitis (NASH), management techniques focus mostly on altering one's lifestyle. In order to assess the safety, pharmacokinetics, and pharmacodynamics of pegozafermin (BIO89-100), a glycoPEGylated FGF21 analogue, in patients with NASH, researchers undertook this study.

Adults (aged 21–75) with NASH with stage F1–F3 fibrosis or non-alcoholic fatty liver disease and a high risk of NASH (referred to in this study as phenotypic NASH) because of central obesity with type 2 diabetes, central obesity with increased alanine aminotransferase (ALT), or central obesity with a Fibroscan score of 7 kPa or greater were enrolled in this randomised, double-blind, placebo– Using an interactive web response system, patients were centrally randomised to receive either placebo or subcutaneously injected pegozafermin (3, 9, 18, or 27 mg once weekly; 18 or 36 mg once every two weeks) for 12 weeks. The safety, tolerability, and pharmacokinetics of pegozafermin were the main objectives.

The key findings of this study were;

1. Mildly increased hunger, which was not linked with weight gain and occurred in ten (16%) of the 63 people in the pooled pegozafermin group but not in any of the 18 participants in the pooled placebo group, was the most frequent treatment-related side event. 

2. Due to a negative incident, two patients stopped their treatment (one each in the 27 mg once weekly and 18 mg once every 2 weeks groups). 

3. There were no fatalities or major adverse effects linked to the treatment. We noticed dose-proportional pharmacokinetics. 

4. Of the 63 subjects who received pegozafermin, anti-drug antibodies were found in 41 (65%). 

5. By week 13, pegozafermin significantly decreased the absolute differences in hepatic fat fraction measured using least squares means (LSM) compared to a combined placebo.

In conclusion, Pegozafermin should be examined in more detail in NASH patients.

Reference: 

Loomba, R., Lawitz, E. J., Frias, J. P., Ortiz-Lasanta, G., Johansson, L., Franey, B. B., Morrow, L., Rosenstock, M., Hartsfield, C. L., Chen, C.-Y., Tseng, L., Charlton, R. W., Mansbach, H., & Margalit, M. (2022). Safety, pharmacokinetics, and pharmacodynamics of pegozafermin in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 1b/2a multiple-ascending-dose study. In The Lancet Gastroenterology & Hepatology. Elsevier BV. https://doi.org/10.1016/s2468-1253(22)00347-8