CAMBRIDGE, Mass.– Boston Pharmaceuticals, a clinical-stage biopharmaceutical company developing differentiated molecules addressing serious liver diseases, today announced new data supporting BOS-580, its investigational, long-acting fibroblast growth factor 21 (FGF21) analog for the treatment of non-alcoholic steatohepatitis (NASH). Results support a once-monthly dosing schedule for BOS-580 and the positive effects of treatment for people living with NASH who are at risk for or have type 2 diabetes. These data are being presented on Saturday, Nov. 11, 2023, at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting® in Boston.
BOS-580 is a long-acting, highly engineered FGF21 analog administered via a once-monthly subcutaneous injection. BOS-580 is designed to reduce liver fat content, liver inflammation as evidenced by biomarkers of liver injury and fibrosis and improve metabolism as evidenced by the impact on metabolic biomarkers in patients with NASH.
“The results we are presenting at AASLD reinforce our belief in the potential of BOS-580 as a once-monthly treatment option for NASH patients, offering comprehensive disease management with a favorable safety profile,” said Sophie Kornowski, PharmD, CEO of Boston Pharmaceuticals. “We are currently evaluating a once-monthly dosing regimen for BOS-580 and its effect in people living with NASH who have liver fibrosis, with the plan to rapidly continue the development and initiate pivotal clinical trials.”
Research has shown that individuals with non-alcoholic fatty liver disease (NAFLD), which can lead to NASH, are at a higher risk of developing type 2 diabetes,1 and two-thirds of people with type 2 diabetes also have NAFLD.2 In this analysis, recognized by AASLD as a poster of distinction, the effects of BOS-580 treatment on glycemic control biomarkers and liver steatosis reduction were examined in diabetic sub-populations enrolled in Part A of a randomized, double-blind, placebo-controlled Phase 2a study in patients with phenotypic NASH. Study participants (n=102) were classified into three different subgroups – normal, pre-diabetic, diabetic – according to their HbA1c values and received treatment with BOS-580 (once-monthly or bi-weekly subcutaneous doses) or placebo.
Compared to placebo over 12 weeks:
- BOS-580 treatment numerically improved insulin resistance, as shown by the reduction of C-peptide (a surrogate for insulin production) levels, across all diabetic sub-populations.
- BOS-580 treatment numerically improved the percentage of patients who maintained or achieved HbA1c normalization (<5.7%) in the normal and pre-diabetic sub-populations and led to a greater portion of patients in the diabetic sub-population who were able to reduce their HbA1c to <6.5% compared to the placebo group.
- The normal, pre-diabetic and diabetic sub-populations showed very similar reductions (57-66%) in hepatic fat fraction (HFF) after 12 weeks of BOS-580 treatment. And more than 64% of patients in each sub-population treated with BOS-580 achieved ≥50% reductions in HFF.
- No cases of hypoglycemia were observed in patients treated with BOS-580.
“BOS-580 treatment appears promising in maintaining healthy HbA1c levels among patients with phenotypic NASH, irrespective of their concurrent type 2 diabetes status. Our analysis showed that BOS-580 performed consistently well across all diabetic sub-populations in the Phase 2a clinical study,” said Rohit Loomba, M.D., MHSc, Professor of Medicine, Chief in the Division of Gastroenterology and Hepatology, and Director of MASLD Research Center at University of California, San Diego. “These results are encouraging, especially considering the high prevalence of type 2 diabetes among people living with NASH.”
A second analysis presented at AASLD evaluated population pharmacokinetics (Pop-PK) of BOS-580 in patients with phenotypic NASH enrolled in the Phase 2a trial (n=102) and assessed the effects of different BOS-580 doses and once-monthly vs. bi-weekly subcutaneous dosing regimens on pharmacodynamic (PD) biomarkers, HFF, PRO-C3 (a biomarker of active fibrogenesis) or ALT (alanine aminotransferase, a marker of liver injury).
Once-monthly and bi-weekly dosing regimens for long-acting BOS-580 predicted a similar effect on efficacy biomarkers for NASH based on Pop-PK/PD modeling, supporting the continued development of a once-monthly dose. Differences observed for PD response between the 300 mg and 150 mg once-monthly doses were similar. Results indicate that data were highly correlated with no obvious bias across the Pop-PK and PK/PD models, with most data points within the 90% confidence interval.
