Rivus Pharmaceuticals announced positive topline results from its Phase 2 M-ACCEL trial, demonstrating that HU6, an investigational controlled metabolic accelerator, met its primary endpoint with statistically significant reductions in liver fat content in patients with metabolic dysfunction-associated steatohepatitis (MASH). The 6-month study showed liver fat reductions of p<0.01 across all three treatment groups compared to placebo, with a statistically significant proportion of patients achieving greater than 30% liver fat reduction—a clinically meaningful marker associated with MASH resolution and fibrosis improvement.
Unique Fat-Selective Weight Loss Profile
HU6 demonstrated a distinctive therapeutic profile by achieving entirely fat-specific weight loss with no significant change in lean muscle mass at any dose level. This contrasts favorably with incretin-based therapies, which have been shown in clinical studies to significantly reduce lean muscle mass. Approximately three-quarters of the fat loss occurred in the visceral fat compartment, which is most strongly associated with the harmful consequences of obesity and cardiometabolic disease.
"Treatment with HU6 significantly reduced body weight, body fat and abdominal visceral fat with preservation of skeletal muscle mass versus placebo and was well tolerated," according to the company's announcement. The therapy works as an oral, once-daily small molecule that increases resting metabolic rate, helping the body burn fat without requiring behavioral intervention or leading to muscle degradation.
Secondary Endpoint Achievements
Despite not being powered to evaluate secondary endpoints, the M-ACCEL trial demonstrated favorable trends across multiple cardiometabolic parameters. HU6 treatment was associated with reductions in body weight, visceral fat mass, blood pressure, and hemoglobin A1c, consistent with having a broadly beneficial profile to address the dysmetabolism characteristic of MASH.
The efficacy of HU6 was consistent across patient populations, with approximately two-thirds of patients having Type 2 diabetes at baseline. The therapy showed similar effectiveness in diabetic patients compared to those who were non-diabetic at baseline.
Clinical Significance and Expert Perspective
"Obesity is a key driver of poor outcomes in patients with MASH, a progressive and difficult to manage disease that can lead to cirrhosis, liver failure and premature death," said Mazen Noureddin, M.D., Professor of Medicine at Houston Methodist Hospital and Co-Chairman of the Board of the Summit and Pinnacle Clinical Research Networks. "Patients in the M-ACCEL study achieved a statistically significant reduction in liver fat content with HU6 compared to placebo, with the majority reaching more than a 30% reduction, which has been shown to be a clinically meaningful result associated with MASH resolution and fibrosis improvement."
Safety Profile and Development Timeline
HU6 demonstrated a favorable safety profile consistent with previous studies, with no treatment-related serious adverse events reported. The overall safety database for HU6 now encompasses more than 450 patients across clinical development programs.
"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," said David Grainger, Ph.D., Chairman of Development at Rivus Pharmaceuticals. "Equally important, these data provide continued confirmation of the potential of HU6, and our pipeline of Controlled Metabolic Accelerators, to deliver entirely fat-specific weight loss with a marked propensity for visceral fat reduction for people with obesity and resulting cardiometabolic disease."
Study Design and Patient Population
The randomized, double-blind, placebo-controlled Phase 2 M-ACCEL trial enrolled 221 adult patients across 22 clinical sites in the United States. Patients were randomized 2:1:2:2 into four treatment groups: placebo, HU6 150 mg, HU6 300 mg, or HU6 450 mg, with treatment duration of six months (26 weeks). The primary endpoint measured percent change from baseline in liver fat as assessed by magnetic resonance imaging liver proton density fat fraction (MRI-Liver PDFF).
MASH affects approximately 5% of U.S. adults and is rapidly becoming the leading cause of liver transplantation. The disease is characterized by an accumulation of excess fat cells in the liver and is closely linked to obesity, with increased body mass index being one of the most important risk factors along with cardiovascular disease and Type 2 diabetes.
Rivus plans to leverage learnings from the M-ACCEL trial to inform next steps in HU6's clinical development and will present detailed data from the trial at an upcoming medical meeting.
