HU6 for Patients with NAFLD and Elevated BMI, with Mazen Noureddin, MD, MHSc

Results from the phase 2a study of HU6 in patients with nonalcoholic fatty liver disease (NAFLD) and elevated body mass index (BMI) showed significant reductions in liver fat and body weight after 61 days of treatment compared to placebo, according to an announcement from Rivus Pharmaceuticals on October 5, 2023.¹

The randomized, double-blind, placebo-controlled trial was conducted at a single clinical community site in St Paul, Minnesota, and enrolled 80 adults aged 28 to 65 years with a BMI of 28 to 45 kg/m2, a FibroScan controlled attenuation parameter score of > 270 decibels per meter, and at least 8% liver fat by MRI-proton density fat fraction (MRI-PDFF). Participants were randomly assigned 1:1:1:1 to either once-daily HU6 100 mg, HU6 300 mg, HU6 450 mg, or matching placebo by oral administration for 61 days.¹

​​In total, 20 patients were assigned to placebo, 20 to HU6 150 mg, 21 to HU6 300 mg, and 19 to HU6 450 mg. Upon analysis, the relative mean change in liver fat content from baseline to day 61 was –26.8% (standard deviation [SD], 17.4) for the HU6 150 mg group, –35.6% (SD, 13.8) for the HU6 300 mg group, –33.0% (SD, 18.4) for the HU6 450 mg group, and 5.4% (SD, 19.8) for the placebo group. Investigators pointed out similar results in the high baseline hemoglobin A1C (HbA1c) subgroup, noting increased responder rates were associated with the 300 mg (75%) and 450 mg (86%) doses versus the 150 mg dose (43%) and all were significant compared with placebo (0%; all P < .0001).¹

In the pooled HU6 dose group, 36 (61%) participants had at least a 30% reduction in liver fat from baseline to day 61, with investigators pointing out greater responder rates were associated with the 300 mg (71%) and 450 mg (72%) doses. Compared with placebo, differences in least squares mean change of whole-body adiposity were –.37% (95% confidence interval [CI], –1.26 to .51) in the HU6 150 mg group (P = .40), –1.03% (95% CI, –1.90 to –.16) in the HU6 300 mg group (P = .021), and –1.49% (95% CI, –2.38 to –.60) in the HU6 450 mg group (P = .0014).¹

The editorial team of HCPLive Hepatology sat down with primary investigator Mazen Noureddin, MD, MHSc, medical director of the Houston Research Institute, for more insight into study results and the use of HU6 for the treatment of NAFLD.

References:

1. Noureddin M, Khan S, Portell F, et al. Safety and efficacy of once-daily HU6 versus placebo in people with non-alcoholic fatty liver disease and high BMI: a randomised, double-blind, placebo-controlled, phase 2a trial. Lancet Gastroenterol Hepatol 2023. https://doi.org/10.1016/S2468-1253(23)00198-X
2. Brooks, A. HU6 Reduces Liver Fat, Body Weight in Patients with NAFLD with High BMI. HCPLive. October 6, 2023. Accessed October 9, 2023.