Rivus Pharmaceuticals has announced positive data from its Phase IIa HuMAIN trial, indicating that its investigational drug, HU6, promotes weight loss while preserving muscle mass in obese patients with heart failure with preserved ejection fraction (HFpEF). The results, presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2024, highlight HU6's potential as a novel treatment for this challenging patient population.
The HuMAIN trial (NCT05284617) was a Phase IIa, double-blind, placebo-controlled, dose-escalation study that enrolled 67 patients across 15 sites in the US. Participants received either HU6 or a placebo over 19 weeks, with doses escalating from 150 mg to 300 mg and finally to 450 mg daily. The primary endpoint was statistically significant weight loss, which the trial successfully met. Key secondary endpoints included changes in blood pressure, markers of atherosclerotic cardiovascular disease, and cardiac structure and function.
Muscle-Sparing Effects
A significant finding from the trial was the muscle-sparing effect of HU6. Patients treated with the 450mg dose experienced statistically significant reductions in fat mass and visceral fat without a corresponding decrease in lean body mass. This is particularly important in HFpEF patients, as muscle loss is associated with increased mortality. Current treatments like GLP-1 receptor agonists, while effective for weight loss, can lead to reductions in muscle mass, making HU6 a potentially valuable alternative.
Impact on Cardiovascular Health
The HuMAIN trial also demonstrated benefits in several key secondary endpoints. Patients treated with HU6 experienced improvements in systolic and diastolic blood pressure, as well as key markers of atherosclerotic cardiovascular disease. Echo and MRI measures of cardiac structure and function also showed positive trends. These findings suggest that HU6 may have a broader impact on cardiovascular health beyond weight loss.
Additional Observations
Data indicated a trend toward improvement in inflammation, with a 3 mg/L improvement in high sensitivity C-reactive protein (CRP) in the HU6-treated population versus placebo. There was also a trend toward improvement in the 6-minute walk distance (6MWD). HU6 was generally well tolerated, consistent with previous studies.
HU6: A Controlled Metabolic Accelerator
HU6 is a novel, oral, once-daily, potentially first-in-class investigational treatment classified as a Controlled Metabolic Accelerator (CMA). CMAs are designed to increase resting metabolic rate, leading to increased energy consumption primarily from fat. This mechanism aims to promote sustained body fat loss while preserving muscle mass. Rivus Pharmaceuticals is focusing the clinical development of HU6 on metabolic diseases with high morbidity and unmet treatment needs, including obesity-related HFpEF and metabolic dysfunction-associated steatohepatitis (MASH).
Future Directions
Rivus Pharmaceuticals plans to engage with health authorities in 2025 to discuss the design of a Phase 3 study of HU6 in obesity-related HFpEF. The company aims to further evaluate the drug's efficacy in improving functional status and clinical outcomes in this growing patient population. While a treatment specifically indicated for obesity-related HFpEF remains absent, HU6 represents a promising approach to address the complex metabolic and cardiovascular challenges associated with this condition.
According to Jayson Dallas, MD, CEO of Rivus, the HuMAIN study results support the potential differentiating profile of HU6 in HFpEF, suggesting it could be the first disease-modifying treatment for this debilitating syndrome.
