Rivus Pharma Publishes Phase 2a HuMAIN Trial of HU6 for Obesity-Linked Heart Failure in JAMA Cardiology

Rivus Pharmaceuticals has announced promising results from its Phase 2a HuMAIN clinical trial for HU6, an innovative treatment aimed at addressing heart failure with preserved ejection fraction (HFpEF) linked to obesity. Published in JAMA Cardiology, the study highlights HU6's effectiveness in reducing body fat, particularly visceral fat, while maintaining skeletal muscle mass. These findings are significant given the role excess body fat plays in HFpEF's pathology, a condition with limited treatment options.

HU6 is a novel oral therapy categorized as a Controlled Metabolic Accelerator (CMA), a class of drugs developed to selectively reduce body fat. In this trial, HU6 demonstrated superior results compared to placebo over a 19-week period. Participants showed reductions in body weight, fat mass, and visceral fat, with body composition improvements being a standout outcome. Importantly, there were no significant changes in lean body mass or skeletal muscle, affirming HU6's ability to preserve muscle while targeting fat.

The lead author, Dr. Ambarish Pandey, emphasized the potential impact of HU6 in addressing visceral adiposity, which is recognized as a contributing factor to HFpEF's progression. The trial recorded a notable body weight reduction of 6.8 pounds compared to 0.5 pounds with placebo and showed a decrease in total fat mass and visceral fat percentage. MRI assessments indicated a decrease in abdominal visceral adipose tissue with HU6.

The study also explored secondary endpoints assessing cardiac function improvements and revealed enhancements in left ventricular systolic function, right ventricular function, and blood pressure reductions. These cardiac benefits suggest HU6 could modify the disease beyond mere weight loss, potentially improving the quality of life for HFpEF patients, who often experience physical limitations.

Safety data from the trial were consistent with previous studies, showing HU6 was well-tolerated among participants, who were typically elderly, obese, and managing multiple health conditions. The rate of serious adverse events was low, with four HU6 recipients and one placebo participant experiencing unrelated serious adverse events.

Jayson Dallas, CEO of Rivus Pharmaceuticals, noted the significance of these findings, highlighting HU6's potential as a transformative treatment for HFpEF. The study's positive results, especially regarding cardiac improvements, position HU6 as a promising candidate for addressing this challenging condition.

In addition to the HuMAIN trial, Rivus Pharmaceuticals is progressing with another study, the Phase 2 M-ACCEL trial, which focuses on metabolic dysfunction-associated steatohepatitis (MASH). The company anticipates releasing topline results from this trial in mid-2025.

The HuMAIN trial was conducted across multiple U.S. sites, enrolling 66 participants aged 30 and above, with an average BMI of 39.4 kg/m2 and average body weight of 245 pounds. The primary endpoint of the trial was the change in body weight from baseline to 19 weeks, while secondary endpoints included assessments of peak oxygen uptake, body composition, and other health indicators.

HFpEF, prevalent in Western countries, is characterized by reduced exercise capacity and diminished quality of life, with obesity as a major risk factor. Current weight loss strategies often inadvertently reduce muscle mass, complicating treatment for elderly and frail HFpEF patients. HU6's approach, targeting fat loss while maintaining muscle, offers a new avenue for improving patient outcomes.

Overall, the promising results from Rivus Pharmaceuticals' HuMAIN trial underscore HU6's potential as a groundbreaking treatment for obesity-related HFpEF, setting a hopeful precedent for future therapeutic developments in cardiometabolic disease management.