Rivus Pharma's Phase 2a HuMAIN Trial Achieves Weight Loss and Other Goals in Obesity-Related Heart Failure

Rivus Pharmaceuticals Inc., a clinical-stage biopharmaceutical company, has made significant advancements in their research on metabolic health. They recently announced successful results from their Phase 2a HuMAIN clinical trial, which tested the efficacy of HU6, an oral Controlled Metabolic Accelerator (CMA), in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). The trial demonstrated that HU6 achieved its primary endpoint of significant weight reduction while maintaining muscle mass. This breakthrough data will be highlighted at the Heart Failure Society of America's Annual Scientific Meeting in Atlanta from September 27-30, 2024.

Jayson Dallas, M.D., CEO of Rivus Pharmaceuticals, emphasized the importance of reducing visceral fat to alleviate inflammation, a key factor in obesity-related HFpEF. He highlighted that the HuMAIN trial data supports HU6's potential as the first disease-modifying treatment for HFpEF, offering promising implications for a range of cardiometabolic diseases.

The HuMAIN study also achieved several secondary efficacy and pharmacodynamic endpoints, with HU6 showing a consistent safety profile and good tolerability. This reinforces its potential benefits in patients with multiple co-morbidities on various medications. The study's design and rationale were outlined in a recent publication in the European Journal of Heart Failure. Rivus plans to engage health authorities for a Phase 3 study in 2025.

In parallel, Rivus has completed patient enrollment in the Phase 2 M-ACCEL trial, which tests HU6 in patients with metabolic dysfunction-associated steatohepatitis (MASH). Results from this study are expected in the first half of 2025. So far, over 400 patients have participated in Rivus' HU6 clinical development program.

The Phase 2a HuMAIN trial was a randomized, double-blind, placebo-controlled, parallel-group study evaluating HU6's safety, tolerability, pharmacodynamics, and pharmacokinetics. The trial involved 66 participants aged 30 and above with a BMI over 30 kg/m², who received daily doses of HU6 or placebo for 134 days. Primary efficacy was measured through weight reduction, while secondary endpoints included exercise capacity, quality of life, body composition, cardiac function, and markers of cardiometabolic dysfunction. The study was conducted across 22 clinical sites in the United States.

HFpEF is a chronic syndrome marked by severely reduced exercise capacity, significantly affecting the quality of life. Obesity is a major risk factor for HFpEF, with systemic inflammation from visceral fat contributing to its development. The current survival rate for hospitalized HFpEF patients is approximately two years. Traditional weight loss methods like dieting and bariatric surgery often result in muscle mass loss, which can further impair function in elderly, frail patients with HFpEF.

The Phase 2 M-ACCEL trial is another randomized, double-blind, placebo-controlled study evaluating HU6 in MASH patients. It includes 221 adult participants who are randomized into different treatment groups and assessed over six months. The primary endpoint is the change in liver fat, with secondary endpoints including body weight, glycemic control, liver fibrosis, body composition, and inflammatory markers. The study aims to evaluate HU6's safety, tolerability, pharmacodynamics, and pharmacokinetics across approximately 20 clinical sites in the U.S.

Rivus Pharmaceuticals is pioneering a new class of therapies known as Controlled Metabolic Accelerators (CMAs). These oral small molecules are designed to increase resting metabolic rate, primarily targeting fat for energy consumption without affecting muscle mass. This unique mechanism addresses multiple cardiometabolic conditions linked to adiposity by leveraging mitochondrial uncoupling, which can account for 20%-40% of resting caloric consumption. Initial human data has shown that CMAs can provide fat-selective weight loss, improve insulin sensitivity, and reduce oxidative stress and inflammation.

HU6, Rivus' lead CMA, is intended as a foundational therapy for various metabolic diseases, including cardiac, liver, diabetes, and obesity-related conditions. Clinical trials have demonstrated HU6's ability to significantly reduce liver fat and body weight without affecting lean muscle mass, along with improvements in systemic inflammation and metabolic markers. The current focus is on treating obesity-related HFpEF and MASH, addressing significant treatment needs in metabolic diseases.