Rivus Pharmaceuticals’ fat-busting, muscle-sparing drug candidate reduced liver fat in a phase 2 trial while showcasing the drug's obesity potential.
The biotech evaluated the candidate, dubbed HU6, in doses of either 150 mg, 300 mg or 450 mg in the mid-stage study of 221 adults with metabolic dysfunction-associated steatohepatitis (MASH) over six months. The trial showed a statistically significant reduction in liver fat compared to placebo—equivalent to a p value of less than 0.01—across the three dose cohorts, hitting the study’s primary endpoint.
The proportion of patients who saw a more than 30% reduction in their liver fat was also statistically significant, Rivus explained in a June 24 release.
Although the phase 2 study was not powered to determine reductions in body weight, fat mass and blood pressure, the trial also hit these endpoints. Importantly, HU6 was “associated with entirely fat-specific weight loss,” according to Rivus.
Specifically, three-quarters of the fat loss seen in the trial was visceral fat, according to the biotech. This suggests HU6 has an attractive profile at a time when many pharmas are chasing the holy grail of obesity drugs that don’t reduce muscle mass.
HU6 is a controlled metabolic accelerator, meaning it is designed to increase a patient’s resting metabolic rate and boost the body’s conversion of fat into energy. The candidate already secured a phase 2 win last year by reducing the weight of patients with obesity-related heart failure.
“The topline results from M-ACCEL, the longest study of HU6 to date, indicate that HU6 has a competitive efficacy and safety profile for the treatment of MASH,” Rivus’ Chairman of Development David Grainger, Ph.D., said in this morning's release.
“Equally important, these data provide continued confirmation of the potential of HU6, and our pipeline of controlled metabolic accelerator, to deliver entirely fat-specific weight loss with a marked propensity for visceral fat reduction for people with obesity and resulting cardiometabolic disease,” Grainger added.
There has been a lot of crossover in the MASH and weight loss spaces in recent months. Terns Pharmaceuticals shared preclinical data suggesting its ex-MASH drug could be effective against obesity, while a South Korean biotech’s GLP-1 candidate has managed a similar feat to HU6 by both reducing liver fat for MASH patients and helping them lose weight.
Meanwhile, Novo Nordisk is awaiting an FDA decision on approving semaglutide, the ingredient in its blockbuster GLP-1 weight loss drug Wegovy, for MASH after it demonstrated improvements in liver fibrosis in a phase 3 trial.