Rivus Pharmaceuticals has reported positive data from a Phase IIa trial, in which its therapy HU6 demonstrated fat and weight reduction in obese subjects.
The Phase IIa metabolic study is intended to support multiple Phase IIb trials in metabolic disease including type 2 diabetes, severe hypertriglyceridemia, and nonalcoholic steatohepatitis, according to the company website. HU6 is described as a controlled metabolic accelerator (CMA).
The placebo-controlled, randomised, double-blind, 61-day Phase IIa trial analysed the safety and efficacy of 150mg, 300mg and 450mg dose levels of HU6 in obese subjects with raised liver fat.
It enrolled 80 subjects aged between 28 and 65 years who were randomised to receive one of three doses of HU6 or a placebo.
Findings showed that the Phase IIa metabolic trial met the primary endpoint of reducing liver fat by MRI-PDFF and the secondary endpoint of reduction in body weight and fat by abdominal MRI.
Furthermore, a statistically significant decline in liver fat was observed at all the three tested dose levels of HU6.
As against placebo relative decline in liver fat of 2% and responder rate of 5%, 150mg, 300mg and 450mg doses of HU6 offered relative decline in liver fat of 33%, 43%, and 40% with responder rates of 40%, 71% and 72%, respectively.
At eight weeks, HU6 offered substantial liver, visceral, and total body fat reduction without conserving skeletal muscle mass, causing considerable total weight reductions.
Subjects who had high HbA1c levels experienced at the baseline were also observed to have significant weight and fat loss.
In addition, considerable dose-dependent decline in glycated albumin and inflammation marker high sensitivity C-reactive protein (hsCRP) were reported.
At all tested dose levels in the trial, HU6 was found to be well-tolerated.
Rivus Pharmaceuticals chief scientific officer Shaharyar Khan said: “This trial provides compelling proof of clinical concept for the efficacy and safety of mitochondrial uncoupling with HU6, our first in class CMA.
“Given early indications that this biology may reverse insulin resistance and systemic inflammation, we can now explore whether reducing visceral and organ fat can provide clinical benefits to patients across a host of cardiometabolic diseases.”
The company intends to progress its HU6 clinical programme with a Phase IIa trial in heart failure with preserved ejection fracture as well as Phase IIb trials in type 2 diabetes and non-alcoholic steatohepatitis in the first half of this year.
In November last year, Rivus reported positive data from single and multiple ascending dose portions of the Phase I trial of HU6.