Pegozafermin improves fibrosis in patients with NASH, could advance to phase 3 development
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Key takeaways:
- Improvement in fibrosis occurred in up to 27% of patients treated with pegozafermin vs. 7% on placebo.
- Nonalcoholic steatohepatitis resolved in up to 37% of patients treated with pegozafermin vs. 2% on placebo.
Subcutaneous pegozafermin at weekly and biweekly doses improved fibrosis at 24 weeks vs. placebo among patients with biopsy-confirmed nonalcoholic steatohepatitis, supporting the therapy’s advancement to phase 3 development, data showed.
“Pegozafermin, a long-acting glycopegylated recombinant fibroblast growth factor 21 analogue, is being developed for the treatment of NASH and severe hypertriglyceridemia,” Rohit Loomba, MD, MHSc, director of the NAFLD Research Center at the University of California, San Diego, and colleagues wrote in The New England Journal of Medicine. “A phase 1b-2a study involving patients with NASH did not show safety concerns and suggested that pegozafermin therapy may improve hepatic steatosis, markers of inflammation and fibrosis, circulating lipid levels and glycemic control.”
In a phase 2b, randomized, double-blind, placebo-controlled trial at 61 U.S. sites, researchers enrolled 222 patients (mean age, 55.6 years; 39% men) with noncirrhotic, biopsy-confirmed NASH and moderate to severe fibrosis. Participants received subcutaneous pegozafermin 15 mg (n = 21) or 30 mg (n = 73) weekly, pegozafermin 44 mg (n = 57) biweekly or placebo (n = 71) for 24 weeks.
Studied outcomes included improvement in fibrosis of at least one stage with no worsening of NASH, NASH resolution without worsening of fibrosis and safety of pegozafermin.
At 24 weeks, 7% of patients in the placebo group had improved fibrosis compared with 22% in the pegozafermin 15 mg group (14 percentage points difference; 95% CI, –9 to 38), 26% in the 30 mg group (19 percentage points difference; 95% CI, 5-32) and 27% in the 44 mg group (20 percentage points difference; 95% CI, 5-35).
Researchers also reported NASH resolution without worsening of fibrosis among 37% of patients in the 15 mg group (35 percentage points difference; 95% CI, 10-59), 23% in the 30 mg group (21 percentage points difference; 95% CI, 9-33) and 26% in the 44 mg group (24 percentage points difference; 95% CI, 10-37), compared with 2% in the placebo group.
Further, results showed a drop in nonalcoholic fatty liver disease activity score of at least 2 points without worsening of fibrosis among 37%, 65% and 62% of patients in the 15 mg, 30 mg and 44 mg groups, respectively, vs. 24% in the placebo group, as well as at least a 50% reduction in liver fat among 63% in the 30 mg group and 58% in the 44 mg group vs. 12% on placebo.
The most common adverse events associated with treatment were nausea and diarrhea.
“In this phase 2b trial, pegozafermin treatment for 24 weeks led to improvements in fibrosis with both weekly and every 2-week administration in patients with biopsy-confirmed NASH,” Loomba and colleagues concluded. “A potential for administration once every 2 weeks may increase patient convenience and adherence to treatment.”
They continued: “Results of this trial may be informative for guiding dose selection for larger and longer phase 3 trials involving patients with NASH.”
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