Rivus Pharmaceuticals will push HU6 into Phase III development and is looking to engage with regulatory authorities and launch a late-stage study next year in obesity-related heart failure with preserved ejection fraction.
Rivus Pharmaceuticals on Tuesday announced that its drug candidate HU6 aced the Phase IIa HuMAIN trial, significantly reducing body weight in patients with obesity-related heart failure.
The Virginia-based biotech did not provide specific data in its announcement, only revealing that HU6 was able to elicit a “statistically significant weight reduction.” Rivus’ investigational treatment also hit key secondary efficacy and pharmacodynamic endpoints and was well-tolerated with a favorable safety profile overall.
Rivus will present data from HuMAIN at a late-breaking plenary session at the upcoming Heart Failure Society of America Annual Scientific Meeting in September 2024.
CEO Jayson Dallas in a statement said that HuMAIN’s readout “strongly supports the potential of HU6 to be the first disease-modifying treatment for HFpEF [heart failure with preserved ejection fraction] by enabling fat-specific weight loss.” The findings also reinforce the possibility of using HU6 “in a broad range of cardiometabolic diseases with significant morbidity and limited treatment options,” according to Dallas.
Rivus said it will push HU6 into Phase III development and is “on track” to engage with regulatory authorities and launch the late-stage study in obesity-related HFpEF next year.
Designed to be orally available, HU6 is Rivus’ lead controlled metabolic accelerator (CMA) candidate which works by raising a patient’s resting metabolic rate, boosting energy consumption from fat. According to the biotech’s website, weight loss from CMAs is fat-specific and muscle-preserving, leading to better glycemic control and lower oxidative stress and inflammation.
CMAs are designed to take advantage of a cellular metabolic process called mitochondrial uncoupling, which makes up 20% to 40% of resting caloric use, according to Rivus. Unlike restricting calorie intake via dietary adjustments or appetite-altering medications, relying instead on mitochondrial uncoupling selectively burns fat without reducing muscle mass, the company contends.
In October 2023, Rivus published Phase IIa data for HU6 in The Lancet Gastroenterology & Hepatology, demonstrating that in patients with non-alcoholic fatty liver disease and a high body mass index a once-daily dose of the oral CMA significantly lowered liver fat content and body weight without lean muscle mass loss. HU6 also improved metabolism and inflammatory markers.
In addition to obesity and heart failure, Rivus is assessing HU6 in metabolic dysfunction-associated steatohepatitis, for which it has recently completed enrollment in the Phase II M-ACCEL trial. The mid-stage study is testing three doses of HU6 against placebo and a topline readout is expected in the first half of 2025.
