The US Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) to pegozafermin (89bio Inc.) for the treatment of patients with nonalcoholic steatohepatitis (NASH), according to a September 21, 2023, announcement from the manufacturer.
Pegozafermin is an investigational long-acting glycoPEGylated fibroblast growth factor 21 (FGF21) analogue. FGF21 is an endogenous hormone that regulates multiple metabolic pathways and cellular processes. Pegozafermin is engineered using proprietary glycoPEGylated technology that is intended to extend the half-life, according to the manufacturer.
The FDA’s designation is supported by safety and efficacy data from the phase 2b ENLIVEN trial, which enrolled 222 persons aged 21-75 years with biopsy-confirmed NASH and stage F2 or F3 fibrosis. Participants were randomly assigned to receive subcutaneous pegozafermin 15 mg or 30 mg weekly, pegozafermin 44 mg once every 2 weeks, or placebo on a weekly or biweekly basis.
Results showed that, compared with placebo, the 44 mg every-2-week and 30 mg weekly doses were associated with statistically significant changes on both primary histology endpoints: the proportion of participants with histological resolution of NASH without worsening of fibrosis (26% and 23%, respectively, vs 2%) and the proportion of participants with ≥1 stage decrease in fibrosis stage with no worsening of NASH (27% and 26%, respectively, vs 7%). The most common adverse events in the trial were nausea, diarrhea, and injection-site erythema.
The study also included patients with biopsy-confirmed F4 fibrosis who were not part of the primary analysis but continued in the trial. According to the press release, a descriptive analysis of the data from this population showed that 45% of participants in the pegozafermin group experienced at least 1-stage improvement in liver fibrosis with no worsening of NASH by week 24 compared with zero out of 1 patient in the placebo group.
“We are thrilled with this validation from the FDA awarding pegozafermin with Breakthrough Therapy Designation, which we expect will be advantageous for finalizing our Phase 3 development strategy in NASH following planned discussions with regulatory agencies in the fourth quarter of 2023,” said Rohan Palekar, CEO of 89bio, in the press statement. “We believe pegozafermin is well positioned as a leading FGF21 analog treatment option with demonstrated strong histology data, best-in-class tolerability, and dosing convenience to date.” Paleker sees potential for the treatment to meet the needs of patients with F2/F3 fibrosis as well as those with compensated F4 cirrhosis.