Rivus Pharmaceuticals' Phase 2a HuMAIN Study Achieves Key Milestones in Weight Loss and Other Secondary Endpoints for Patients with Obesity-Related Heart Failure
Rivus Pharmaceuticals announced that its Phase 2a HuMAIN clinical trial for HU6 in patients with obesity-related heart failure with preserved ejection fraction (HFpEF) has successfully achieved its primary goal of weight reduction.
HU6 is an innovative, orally administered, once-daily investigational therapy classified as a Controlled Metabolic Accelerator (CMA), aimed at reducing body fat while preserving muscle mass. The treatment demonstrated a statistically significant reduction in body weight.
The HuMAIN trial not only met its primary endpoint but also achieved several secondary efficacy and pharmacodynamic goals. The safety and tolerability of HU6 were consistent with previous studies, showing a favorable profile even in a patient population with multiple comorbidities and complex medication regimens. The design and rationale behind the HuMAIN study, as well as the use of HU6 in HFpEF, have been detailed in a recent publication in the European Journal of Heart Failure. Rivus Pharmaceuticals is preparing to engage with health authorities in 2025 for a Phase 3 study targeting obesity-related HFpEF.
In addition, Rivus Pharmaceuticals has completed the enrollment phase for its Phase 2 M-ACCEL trial, which is investigating HU6 in patients with metabolic dysfunction-associated steatohepatitis (MASH). The company expects to release topline results from this study in the first half of 2025.
About the Phase 2a HuMAIN Study
The HuMAIN study is a randomized, double-blind, placebo-controlled, parallel-group, dose-escalation Phase 2a clinical trial designed to evaluate the safety, tolerability, pharmacodynamics, and pharmacokinetics of ascending doses of HU6 (150 mg, 300 mg, and 450 mg daily) in patients with obesity-related HFpEF. A total of 66 participants, aged 30 or older with a body mass index (BMI) greater than 30 kg/m², were randomly assigned to receive HU6 or a placebo for 134 days.
The primary efficacy goal of the trial was to assess weight reduction, measured by the change in body weight from baseline to Day 134. Secondary goals included evaluating improvements in exercise capacity, quality of life, body composition, cardiac function/structure, and markers of cardiometabolic dysfunction, such as blood pressure, glucose control, inflammation, lipid levels, and liver enzymes.
About HFpEF
Heart failure with preserved ejection fraction (HFpEF) is a chronic and debilitating condition marked by severely reduced exercise capacity, which significantly impacts quality of life. Obesity is a major independent risk factor for HFpEF and contributes to its rising prevalence worldwide.
Systemic inflammation caused by visceral fat deposits is believed to play a significant role in the development and progression of HFpEF. The average survival rate for hospitalized HFpEF patients is around two years. Traditional weight loss strategies, including dieting, bariatric surgery, and GLP-1 agonists, typically focus on reducing energy intake rather than increasing energy expenditure, often resulting in a loss of muscle mass, which can further impair function in HFpEF patients, who are usually elderly, frail, and already have reduced muscle mass.
About the Phase 2 M-ACCEL Study
The M-ACCEL trial is a randomized, double-blind, placebo-controlled, parallel-group Phase 2 clinical study that assesses the safety and efficacy of three dose levels of HU6 in patients with MASH. A total of 221 adult participants were randomly assigned in a 2:1:2:2 ratio to one of four treatment groups: placebo, HU6 150 mg, HU6 300 mg, or HU6 450 mg, and were treated for six months.
The primary endpoint is the percentage change in liver fat from baseline, as measured by MRI liver proton density fat fraction (MRI-Liver PDFF) at the six-month mark. Secondary endpoints include the impact of HU6 on body weight, glycemic control, liver fibrosis, body composition, metabolic and inflammatory parameters, and patient-reported outcomes.
Comentarios