HuMAIN: HU6 Achieves Significant Weight Loss in Obesity-Related HFpEF

Topline results from the Phase 2a HuMAIN clinical trial showed investigational HU6 met the primary endpoint of weight reduction and secondary endpoints in patients with obesity-related heart failure with preserved ejection fraction (HFpEF).¹

Announced by Rivus Pharmaceuticals on August 13, 2024, HU6 is the company’s lead oral, once-daily, Controlled Metabolic Accelerator (CMA) designed to promote sustained body fat loss, by increasing resting metabolism, while preserving muscle mass.

“Inflammation caused by visceral fat is an important driver of obesity-related HFpEF, and reductions in body fat have been shown to lead to improved outcomes in patients,” said Jayson Dallas, MD, chief executive officer, Rivus Pharmaceuticals. “The goal is to reduce body fat while preserving lean muscle mass, especially in this often fragile and elderly patient population.”

Obesity is a key independent risk factor for HFpEF, with up to 80% of patients with HFpEF in the Western hemisphere experiencing overweight or obesity.² Weight loss approaches for obesity, including dieting, bariatric surgery, and GLP-1 agonist therapy, tend to decrease energy intake, rather than increase expenditure, and tend to reduce muscle mass.

These reductions can impair function in patients with HFpEF, who are typically elderly and frail, and who already exhibit reduced muscle mass.

Clinical development of HU6 has been focused on metabolic diseases with elevated morbidity and the most treatment need, including obesity-related HFpEF and metabolic dysfunction-associated steatohepatitis (MASH)/MASLD, according to the company.¹

The randomized, double-blind, placebo-controlled, parallel-group, dose-escalation Phase 2a HuMAIN trial evaluated the safety, tolerability, pharmacodynamics, and pharmacokinetics of ascending doses of HU6 (150 mg, 300 mg, 450 mg daily) in 66 patients aged ≥30 years with obesity-related HFpEF.

Upon analysis, in the HuMAIN trial, treatment with HU6 met the primary endpoint, leading to a statistically significant weight reduction in patients with obesity-related HFpEF, as determined by the change from baseline in body weight at Day 134.

HU6 also met multiple secondary efficacy and pharmacodynamic endpoints. Safety data demonstrated the tolerability of HU6, with a favorable profile among patients with multiple comorbidities and on concomitant medications.

Rivus has announced it remains on track to engage health authorities for a Phase 3 study in obesity-related HFpEF in 2025. The company also indicated that HuMAIN data will be presented in a Late-Breaking Clinical Trial Plenary Session at the Heart Failure Society of America (HFSA) Annual Scientific Meeting in Atlanta.

“We believe that the HuMAIN data strongly supports the potential of HU6 to be the first disease-modifying treatment for HFpEF by enabling fat-specific weight loss while preserving muscle, reinforcing the possibility for it to be used in a broad range of cardiometabolic diseases with significant morbidity and limited treatment options.”

Rivus additionally announced that patient enrollment had been completed in the randomized, double-blind, placebo-controlled, parallel-group Phase 2 M-ACCEL trial evaluating HU6 in patients with MASH. The company is on track to release topline results from the Phase 2 trial in H1 2025.

In a recent interview with HCPLive, primary investigator Mazen Noureddin, MD, MHSc, medical director of the Houston Research Institute, provided more insight into Phase 2a study results and the use of HU6 for the treatment of MASH.³

References

1. _{Pharmaceuticals R. Rivus Pharmaceuticals’ Phase 2A humain trial meets primary endpoint of weight loss and secondary endpoints in patients with obesity-related heart failure. PR Newswire: press release distribution, targeting, monitoring and marketing. August 13, 2024. Accessed August 13, 2024.}
2. _{Borlaug BA, Jensen MD, Kitzman DW, Lam CSP, Obokata M, Rider OJ. Obesity and heart failure with preserved ejection fraction: new insights and pathophysiological targets. Cardiovasc Res. 2023;118(18):3434-3450. doi:10.1093/cvr/cvac120}
3. _{Abigail Brooks. HU6 for patients with NAFLD and elevated BMI, with Mazen Noureddin, MD, MHSC. HCP Live. October 9, 2023. Accessed August 13, 2024. https://www.hcplive.com/view/hu6-for-patients-with-nafld-and-elevated-bmi-with-mazen-noureddin-md-mhsc.}