VIDEO: Investigational FGF-21 improves liver fat, glycemic control markers in MASH, diabetes
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BOSTON — In this video, Rohit Loomba, MD, MHSc, discusses data supporting once-monthly dosing of BOS-580, an investigational, long-acting fibroblast growth factor-21 analog for treatment of metabolic dysfunction-associated steatohepatitis.
Loomba and colleagues conducted a two-part, randomized, placebo-controlled phase 2a trial to evaluate the effect of BOS-580 (Boston Pharmaceuticals) on glycemic control biomarkers and liver steatosis among individuals with phenotypic MASH, who have or are at risk for diabetes.
“Diabetics have an increased risk for fibrosis progression, and there is an increased risk of severity of liver disease among patients with NAFLD,” Loomba, professor and chief of the division of gastroenterology and hepatology and director of the MASLD Research Center at University of California, San Diego, told Healio. “We wanted to look at whether the response to FGF-21 is similar between diabetics and nondiabetics.”
Researchers assigned 102 patients to one of four subcutaneous doses of BOS-580 (300 mg every 4 weeks, 150 mg every 2 weeks, 75 mg every 2 weeks or 75 mg every 4 weeks) or placebo over 12 weeks. Based on baseline HbA1c values, patients were grouped in subpopulations as normal (HbA1c < 5.7%), prediabetic (HbA1c ≥ 5.7% and < 6.5%) or diabetic (HbA1c ≥ 6.5%).
According to results, C-peptide levels were reduced across all subpopulations treated with BOS-580 vs. placebo, indicating improvement in insulin resistance. HbA1c levels also declined across all groups on BOS-580, with greater reductions in the diabetic subpopulation.
Further, treatment with BOS-580 improved the percentage of participants who maintained or achieved HbA1c normalization, with 31% of patients in the diabetic subpopulation reducing HbA1c to less than 6.5% compared with 11.1% on placebo.
Reduction in hepatic fat fraction (HFF), based on MRI-PDFF, was similar between groups treated with BOS-580, Loomba noted, with a “good response” among those with diabetes. More than 64% of patients in each subpopulation achieved at least 50% reduction in HFF with BOS-580.
“We also want to emphasize that FGF-21 appears to be very potent,” Loomba said, noting BOS-580’s efficacy at once-monthly dosing. “This potency appears to be very similar to what we see with other potent FGF-21s, such as efruxifermin and pegozafermin. For both of those, we have data that this degree of liver fat improvement with FGF-21 leads to improvement in NASH resolution and fibrosis if treated over 20 to 24 weeks. I think we can expect the same if this drug moves forward to a phase 2b study, where we would have histology assessment.”
Loomba continued, “We are very hopeful that these data based on noninvasive biomarkers translate into histologic response.”
Reference:
- Boston Pharmaceuticals announces positive phase 2a data supporting once-monthly dosing with investigational BOS-580 in NASH and treatment effects in diabetic subgroups at AASLD The Liver Meeting 2023. https://www.businesswire.com/news/home/20231110277760/en/Boston-Pharmaceuticals-Announces-Positive-Phase-2a-Data-Supporting-Once-monthly-Dosing-With-Investigational-BOS-580-in-NASH-and-Treatment-Effects-in-Diabetic-Subgroups-at-AASLD-The-Liver-Meeting%C2%AE-2023 Published Nov. 10, 2023. Accessed Dec. 12, 2023.
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Loomba R, et al. BOS-580, an investigational FGF21 analog, improved markers of glycemic control and liver steatosis in a diabetic subpopulation enrolled in a phase 2a double-blind, placebo-controlled study in patients with phenotypic NASH. Presented at: The Liver Meeting; Nov. 10-14, 2023; Boston (hybrid meeting).
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