Rivus Pharma to Present Phase 2a HU6 Data for Obesity-Related Heart Failure at HFSA 2024

Rivus Pharmaceuticals, a clinical-stage biopharmaceutical company focused on metabolic health, has announced new findings from its Phase 2a HuMAIN clinical trial. The study investigates the efficacy of HU6, a novel oral therapy designed to aid in fat reduction while maintaining muscle mass, in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). These results will be highlighted during a Late Breaking Clinical Research Session at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2024 in Atlanta, Georgia.

The HuMAIN trial successfully met its primary goal of significant weight reduction, along with several secondary efficacy and pharmacodynamic endpoints. HU6, administered once daily, is a Controlled Metabolic Accelerator (CMA) that promotes sustained fat loss while preserving muscle tissue. This is particularly beneficial for HFpEF patients, who are often older and more vulnerable. Rivus Pharmaceuticals plans to engage with health authorities in 2025 to discuss the design of a Phase 3 clinical trial for HU6 in this patient population.

Jayson Dallas, M.D., CEO of Rivus Pharmaceuticals, emphasized the importance of these findings, stating, "The HuMAIN study demonstrated that HU6 could achieve fat-specific weight loss while preserving muscle, an essential factor for patients with HFpEF. We are eager to present further data at HFSA 2024, which supports HU6’s potential as the first disease-modifying treatment for HFpEF."

The HuMAIN trial, a randomized, double-blind, placebo-controlled, parallel-group study, included 661 participants (382 women and 28 men) aged 30 and above, all with a body mass index (BMI) greater than 30 kg/m2. Participants were administered HU6 in varying doses (150 mg, 300 mg, 450 mg daily) over 134 days. The primary endpoint was weight reduction, with secondary endpoints assessing improvements in exercise capacity, quality of life, body composition, and several cardiometabolic markers, such as blood pressure, glucose control, inflammation, lipid levels, and liver enzymes. The trial was conducted across 224 clinical sites in the United States.

Detailed results from the HuMAIN study indicate that HU6 was generally well-tolerated among the participants, who often had multiple co-morbidities and were on various medications. The study's design and rationale were published in the European Journal of Heart Failure, highlighting the drug's potential impact on HFpEF treatment.

Heart Failure with Preserved Ejection Fraction (HFpEF) is a chronic condition marked by significantly reduced exercise capacity and deteriorating quality of life. Obesity is a significant independent risk factor for HFpEF, with up to 80% of HFpEF patients in Western countries being overweight or obese. Visceral fat-induced systemic inflammation is believed to play a critical role in the development and progression of HFpEF. Current treatment approaches focusing on weight loss, such as dieting, bariatric surgery, and GLP-1 agonists, tend to reduce both fat and muscle mass, which can be detrimental to elderly HFpEF patients who are already frail.

Rivus Pharmaceuticals is pioneering a new class of therapies called Controlled Metabolic Accelerators (CMAs) to address these issues. CMAs work by increasing the resting metabolic rate, leading to increased energy consumption mainly from fat while preserving muscle mass. This mechanism contrasts with caloric-restriction strategies that reduce both fat and muscle mass. Initial human data indicates that CMAs can provide fat-selective weight loss, improve insulin sensitivity, and significantly reduce oxidative stress and inflammation.

HU6, Rivus Pharmaceuticals’ lead CMA, is an oral therapy designed for daily use. It aims to promote sustainable fat loss while preserving muscle mass, addressing multiple metabolic conditions. Phase 2 results have shown that HU6 significantly reduces liver fat content and body weight without muscle loss, also improving key markers of systemic inflammation and metabolism. The drug has been well-tolerated with mainly mild to moderate side effects.

Currently, Rivus Pharmaceuticals focuses on HU6 for treating metabolic diseases with high morbidity, such as obesity-related HFpEF and metabolic dysfunction-associated steatohepatitis (MASH)/MASLD.