Rivus Pharma Reveals Phase 2a HuMAIN Trial Data Showing HU6 Causes Weight Loss in Obesity-Related Heart Failure

Rivus Pharmaceuticals, a clinical-stage biopharmaceutical company, has announced promising results from its Phase 2a HuMAIN study, examining the effects of HU6 in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). This study, presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2024, met its primary endpoint, demonstrating significant weight loss with HU6.

The HuMAIN trial involved patients with obesity-related HFpEF, a condition characterized by chronic heart failure and systemic inflammation, typically seen in older, obese individuals with multiple health issues. The trial's primary endpoint was to reduce body weight, and HU6 succeeded in achieving statistically significant weight loss compared to placebo. Participants treated with 450 mg of HU6 experienced a notable loss in fat mass and visceral fat, without any significant changes in lean body mass. Additionally, patients showed improvements in blood pressure, cardiovascular disease markers, and cardiac structure and function as measured by echocardiography and MRI.

Dr. Ambarish Pandey, a cardiologist and trial investigator, noted that these results are particularly encouraging given the frailty and multiple medical conditions of the study participants. He highlighted the importance of preserving lean muscle mass in this patient population, stating that the significant reductions in body and visceral fat observed are promising outcomes.

Jayson Dallas, M.D., CEO of Rivus Pharmaceuticals, emphasized that these findings align with previous studies conducted on HU6, including those focusing on metabolic dysfunction-associated steatotic liver disease (MASLD). He noted that HU6 could potentially become the first disease-modifying treatment for HFpEF, given its positive impact on fat reduction while preserving muscle mass.

The HuMAIN trial was a randomized, double-blind, placebo-controlled study involving 66 patients aged 30 and above, with a body mass index (BMI) greater than 30 kg/m². Over three months, participants were administered varying doses of HU6 (150 mg, 300 mg, 450 mg) or a placebo. In addition to weight loss, secondary endpoints included improvements in exercise capacity, quality of life measures, body composition, and various markers of cardiometabolic dysfunction. The results showed significant reductions in fat mass, visceral fat, and key cardiovascular disease markers. These improvements were achieved without significant reductions in lean body mass or an increase in heart rate.

Safety data from the trial indicated that HU6 was well tolerated. Most treatment-emergent adverse events (TEAEs) reported were mild to moderate, with diarrhea, COVID-19, and dyspnea being the most common. Importantly, there were no treatment-related serious adverse events or new cases of cataracts, metabolic fevers, neutropenia, or neuropathy.

HU6 is a Controlled Metabolic Accelerator (CMA), a novel class of investigational therapies designed to increase resting metabolic rate and promote fat loss while preserving muscle mass. By leveraging mitochondrial uncoupling, HU6 increases energy expenditure, primarily from fat, which could address multiple cardiometabolic conditions. Preclinical and clinical studies have shown that HU6 induces fat-selective weight loss, improves insulin sensitivity, and reduces oxidative stress and inflammation.

In addition to HFpEF, Rivus Pharmaceuticals is also investigating HU6 for other metabolic diseases, including metabolic dysfunction-associated steatohepatitis (MASH). The company is conducting the Phase 2 M-ACCEL trial to evaluate HU6's efficacy in reducing liver fat content in patients with MASH, with results expected in the first half of 2025.

In summary, the Phase 2a HuMAIN trial results underscore the potential of HU6 as a promising treatment for obesity-related HFpEF. By effectively reducing fat mass while preserving muscle mass, HU6 could significantly improve the quality of life for patients suffering from this challenging condition.