Novel obesity agent linked to weight loss vs. placebo at 3 months in patients with HFpEF
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Key takeaways:
- HU6, a novel controlled metabolic accelerator, reduced weight at 3 months vs. baseline and vs. placebo in patients with obesity-related HFpEF.
- HU6 was tied to reduced fat mass but not reduced lean body mass.
In a phase 2a trial of patients with obesity-related HF with preserved ejection fraction, a novel controlled metabolic accelerator was associated with weight loss at 3 months compared with placebo.
As Healio previously reported, top-line results of the phase 2a HuMain-HFpEF trial of HU6 (Rivus Pharmaceuticals), which is designed to promote weight loss while preserving muscle mass, were released in August. Ambarish Pandey, MD, associate professor of internal medicine at UT Southwestern Medical Center, presented the full results during a virtual late-breaking clinical research session of the Heart Failure Society of America Annual Scientific Meeting. The in-person meeting was canceled due to Hurricane Helene.
“HU6 is a unique drug because its mechanism of action produces loss of fat mass while preserving lean mass,” Pandey told Healio. “With GLP-1 receptor agonists like semaglutide (Wegovy, Novo Nordisk) and tirzepatide (Zepbound, Eli Lilly), 40% to 50% of weight loss is actually lean mass. That means losing a lot of skeletal muscle. In older patients with HFpEF who have frailty and sarcopenia, that may be problematic.”
Obesity-related HFpEF
HuMain-HFpEF included 66 patients with obesity-related HFpEF (38 women; age range, 38-87 years; mean baseline BMI, 39.4 kg/m2; mean baseline weight, 245 lb) who were randomly assigned to HU6 at an escalating dose up to 450 mg or placebo.
“Obesity has a pathologic and even causal role in the development of HFpEF,” Pandey told Healio. “Visceral adiposity and overall adiposity are very strongly associated with progression and severity of HFpEF. More than 60% of patients with HFpEF have obesity. We targeted HFpEF because of that.”
The primary outcome of weight loss at 19 weeks favored HU6 over placebo in terms of change in body weight (difference, –2.9 kg; 95% CI, –4.7 to –1; P = .003) and percent change in body weight (difference, –2.7%; 95% CI, –4.5 to –1; P = .003), Pandey said during the presentation.
Weight loss at 3 months was significant for patients assigned HU6 compared with baseline (–6.8 lb; P < .0001) and compared with the placebo group (–6.3 lb; P = .003), according to a press release from Rivus Pharmaceuticals.
In addition, fat mass loss at 3 months was significant for patients assigned HU6 compared with baseline (–7.4 lb; P < .0001) and compared with the placebo group (–6.5 lb; P = .0003), according to the release; fat mass loss at 19 weeks favored the HU6 group (difference, –6.9%; 95% CI, –10.3 to –3.5; P = .0001), Pandey said.
In the HU6 group, visceral fat was reduced at 19 weeks compared with the placebo group (difference, –6.6%; 95% CI, –10.5 to –2.8; P = .001) he said.
There was no difference in lean body mass at 3 months in the HU6 group compared with baseline or with the placebo group, according to the researchers.
HU6 was also associated with reduced systolic BP (–8.8 mm Hg; P = .0049) and diastolic BP (–4.1 mm Hg; P = .0546) at 3 months, but there was no difference in heart rate compared with placebo, Pandey and colleagues found.
Also, the researchers found, HU6 was linked to reduced apolipoprotein B, lipoprotein(a) and total cholesterol (P < .05 for all) as well as troponin levels (–84.94 ng/L; P = .0473) at 3 months compared with baseline.
Compared with placebo, HU6 was associated with improved left ventricular mass on MRI (P = .082) and improved LVEF on echocardiography (P = .0007), Pandey and colleagues found.
There were no differences between the groups in exercise metrics or quality of life at 19 weeks, Pandey said during the presentation.
Serious adverse events occurred in 12.1% of the HU6 group and 3.1% of the placebo group, but no events, including one death in the HU6 group, were deemed to be related to the study drug, he said.
‘Favorable effects’ need more study
“These findings suggest that [HU6] can be used to achieve significant reductions in overall adiposity burden, and future trials are needed to evaluate whether these favorable effects on body composition can lead to better clinical and functional outcomes,” Pandey told Healio.
A larger trial of HU6 in patients with HFpEF for a longer duration of time is warranted, he said.
HU6 is also being studied in the phase 2 M-ACCEL trial of patients with metabolic dysfunction-associated steatohepatitis, according to the release.
Reference:
- Rivus Pharmaceuticals announces new clinical data from phase 2a HuMAIN trial demonstrating significant weight loss with HU6 in patients with obesity-related heart failure. https://www.prnewswire.com/news-releases/rivus-pharmaceuticals-announces-new-clinical-data-from-phase-2a-humain-trial-demonstrating-significant-weight-loss-with-hu6-in-patients-with-obesity-related-heart-failure-302262028.html. Published Sept. 30, 2024. Accessed Sept. 30, 2024.
For more information:
Ambarish Pandey, MD, can be reached at ambarish.pandey@utsouthwestern.edu.
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Pandey A, et al. Late breaking clinical research session II. Presented at: The Heart Failure Society of America Annual Scientific Meeting; Sept. 27-30, 2024 (virtual meeting).
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