There’s a new weight loss drug candidate in town, and it’s targeted specifically at obese heart patients. Rivus Pharmaceuticals’ HU6 led to statistically significant weight loss in patients with obesity-related heart failure with preserved ejection fraction (HFpEF) in a mid-stage trial (the HuMAIN study). HFpEF patients have symptoms of HF, such as severely reduced exercise capacity, despite normal or near normal LV ejection fraction.
This novel drug, Rivus says in its press release, “is designed to promote sustained body fat loss while preserving muscle mass.” HU6 is an oral, once-daily potentially first-in-class investigational treatment, a Controlled Metabolic Accelerator (CMA). Rivus’s CMAs are oral small molecules designed to increase resting metabolic rate, which results in increased consumption of energy, primarily from fat.
Rivus says data from the HuMAIN study will be presented in a Late Breaking Clinical Trial Plenary Session at the Heart Failure Society of America (HFSA) Annual Scientific Meeting, September 27–30, 2024, in Atlanta.
According to the World Health Organization, in 2022, one in eight people in the world were living with obesity and worldwide adult obesity has more than doubled since 1990, while adolescent obesity has quadrupled.
Since the launch of GLP-1 agonists (e.g. Ozempic and Wegovy), the weight loss market has been booming. GLP-1s are drugs that signal fullness to the brain and regulate blood sugar so that those taking them will know when to stop eating. Rivus is one of several companies trying to come up with next generation weight loss drugs.
“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. The goal is to reduce body fat while preserving lean muscle mass, especially in this often fragile and elderly patient population,” said Jayson Dallas, MD, chief executive officer, Rivus Pharmaceuticals.
“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.”
In addition to meeting the primary endpoint, the HuMAIN study met several secondary efficacy and pharmacodynamic endpoints. The profile of HU6 was consistent with previous studies. It was well tolerated and had a favorable safety profile in patients who had multiple co-morbidities and were on numerous other medications.
The rationale for the use of HU6 in HFpEF and the design of the HuMAIN study were recently published in the European Journal of Heart Failure. Those authors wrote, “Compared with those without obesity, patients with obesity-related heart failure with preserved ejection fraction (HFpEF) have worse symptoms, haemodynamics, and outcomes. Current weight loss strategies (diet, drug, and surgical) work through decreased energy intake rather than increased expenditure and cause significant loss of skeletal muscle mass in addition to adipose tissue.”
Rivus plans a Phase III study in obesity-related HFpEF in 2025. Additionally, the company has completed patient enrollment in the Phase II M-ACCEL trial of HU6 in patients with metabolic dysfunction-associated steatohepatitis (MASH). The company says topline results from the M-ACCEL study will be announced in the first half of 2025. To date, more than 400 patients have been treated as part of Rivus’ HU6 clinical development program.
