Heart Failure

Rivus HU6 Shows Obesity-HFpEF Potential

Rivus Pharmaceuticals’ HU6 is showing promise as a future obesity-related HFpEF treatment, after topline results from its Phase 2a HuMAIN trial revealed valuable weight, symptom, and cardiometabolic improvements – without the risk of muscle loss.

  • HU6 is an oral Controlled Metabolic Accelerator that promotes weight loss by making energy production less efficient, forcing the body to rev up metabolism to maintain homeostasis, while avoiding muscle loss.
  • The deadly diet pill of the 1930s, DNP, acted through the same pathway but was abandoned because it famously ‘cooked internal organs.’
  • Safe to say Rivus has avoided DNP’s safety concerns, and has already raised over $167M to support HU6’s development.

A key step in Rivus’ HU6 development plan is the HuMAIN trial, which gave 66 people with obesity-related HFpEF either HU6 or a placebo, with dosage escalating throughout the 134 day trial.

  • The study met its primary endpoint, with HU6 patients achieving targeted body weight reductions.
  • HU6 was also well-tolerated, even among these patients with multiple co-morbidities and taking numerous medications.

Perhaps more importantly, the HU6 group achieved a range of obesity and HF-related secondary endpoints, including exercise capacity, quality of life, body composition, cardiac function/structure, and cardiometabolic dysfunction markers (e.g. blood pressure, pulse, glucose control, inflammation, lipid levels, and liver enzymes).

Rivus suggested that these results “strongly support” HU6’s potential to be the first disease-modifying treatment for HFpEF by enabling fat-specific weight loss, while preserving lean muscle mass. 

  • Enabling weight loss without sacrificing muscle mass would give HU6 a unique advantage versus GLP-1s, which are increasingly showing their ability to improve HF outcomes, but also cause these often-fragile patients to lose muscle.
  • Rivus also believes that these results reinforce HU6’s potential to be used in an even broader range of cardiometabolic diseases.

The next steps towards proving HU6’s cardiometabolic potential include the release of the full HuMAIN trial results in September, an ongoing Phase 2 trial focused on MASH patients, and a forthcoming Phase 3 trial further evaluating HU6 in patients with obesity-related HFpEF.

The Takeaway

HU6 has a lot to prove, but these initial results show that it could drive weight loss and cardiometabolic improvements, without sacrificing muscle mass. That’s not something we can say for GLP-1s, bariatric surgery, or even dieting, and it could give HU6 an attractive position in the growing field of obesity-related cardiometabolic treatments.

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