BIO89-100 reduces liver fat in NASH
Weekly (QW) or biweekly (Q2W) treatment with BIO89-100 led to a significantly reduced liver fat and liver fat volume (LFV) in patients with nonalcoholic steatohepatitis (NASH), according to a recent study presented at ENDO 2021.
This phase 1b/2a, double-blind, placebo-controlled, multiple ascending-dose study analysed 81 patients diagnosed with biopsy-proven (n=15) or phenotypic NASH (n=66) who had a baseline liver fat of ≥10 percent, as measured by MRI-PDFF*. Subjects were randomized to receive BIO89-100 QW [3, 9, 18, or 27 mg] or Q2W dosing [18 or 36 mg] (n=62; mean age 51.7 years) or placebo (n=19; mean age 52.6 years) for a 12-week treatment period. [ENDO 2021, abstract P02-53]
At week 13, all BIO89-100 dosing groups experienced significant reductions in liver fat compared with the placebo group (placebo-adjusted relative change, from -46.0 to -70.0 percent [for QW doses] and from -53.0 to -60.0 percent [for Q2W doses]; p<0.001 for all doses), with the most pronounced effect observed in the 27 mg QW dosing group (-70.0 percent).
Majority of the patients treated with BIO89-100 also achieved a clinically meaningful responder rate of ≥30 percent (60.0–86.0 percent and 69.0–88.0 percent for QW and Q2W dosing groups, respectively) and responder rate of ≥50 percent (20.0–71.0 percent and 39.0–50.0 percent, respectively), whereas none was reported with placebo treatment.
BIO89-100 recipients also achieved a significant reduction in LFV at week 13 compared with the placebo recipients (from -36.0 to -65.0 percent [for QW doses] and from -46.0 to -56.0 percent [for Q2W doses] vs 12.0 percent; p<0.001 for all doses).
In a subgroup of patients with elevated ALT+ (>45.0 U/L) at baseline, those on BIO89-100 showed a greater reduction in ALT levels than those on placebo at week 13 (absolute change, -35.0 vs -10.3 U/L; p<0.05).
With regard to lipid profile, particularly those with high triglyceride levels (≥200 mg/dL) at baseline, the BIO89-100 arm demonstrated a decrease in triglyceride (33.0–49.0 percent) and non-HDL cholesterol levels (8.0–29.0 percent).
Fewer patients reported gastrointestinal-related adverse events (AEs), such as diarrhoea and nausea (9.5 percent and 4.8 percent, respectively, vs 11.1 percent), in the BIO89-100 arm vs the placebo arm.
Additionally, two serious AEs were reported, which were both COVID-19 infections, but were considered unrelated to study treatment.
“[Overall,] in subjects with NASH, [both] BIO89-100 [QW and Q2W dosing] led to robust, significant, and clinically meaningful reductions in liver fat and LFV assessed by MRI-PDFF, … with concurrent beneficial effects on lipids and other metabolic parameters,” said the researchers.
“The promising clinical profile of BIO89-100 supports further development in NASH and severe hypertriglyceridaemia,” they added.
*MRI-PDFF: Magnetic resonance imaging-proton density fat fraction
**ALT: Alanine aminotransferase