CHARLOTTESVILLE, Va., and SOUTH SAN FRANCISCO, Calif., June 5, 2026
Rivus Pharmaceuticals announced new preclinical data for RV-8451, its investigational oral GLP-1 receptor agonist for obesity, at the American Diabetes Association (ADA) 2026 Scientific Sessions. The findings demonstrated significant fat-specific weight loss, preservation of lean muscle mass, and no drug-related gastrointestinal adverse events in studies involving diet-induced obese non-human primates (NHPs). The company also confirmed that IND-enabling studies are underway, with an Investigational New Drug (IND) submission targeted for the first quarter of 2027.
RV-8451 Delivers Fat-Selective Weight Loss While Preserving Muscle
In a preclinical study, obese non-human primates treated with RV-8451 for 18 days experienced a 53% reduction in daily food intake, a 9% decrease in body weight, and up to a 20% reduction in fat mass. Importantly, lean muscle mass remained unchanged throughout treatment, highlighting RV-8451’s potential to address one of the major limitations of current obesity therapies. Researchers also observed improvements in cardiometabolic markers, including reductions in alanine transaminase (ALT), triglycerides, and total cholesterol. No drug-related gastrointestinal adverse events were reported.
Head-to-Head Study Shows Advantages Over Orforglipron
A separate 28-day head-to-head study compared RV-8451 with Orforglipron in obese non-human primates. While both treatments achieved similar overall weight loss of approximately 7%, RV-8451 produced a significantly greater reduction in fat mass, achieving a 30% decrease compared with 11% for orforglipron. Additionally, RV-8451 increased lean mass by 4%, whereas animals receiving orforglipron experienced a 6% loss of lean mass. No gastrointestinal adverse events related to RV-8451 were observed, further supporting its differentiated profile.
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Advancing Toward Clinical Development
Rivus believes RV-8451 could become the first muscle-preserving oral non-peptide GLP-1 receptor agonist designed to deliver high-quality, fat-selective, and durable weight loss. The program is intended to address key challenges associated with currently approved GLP-1 therapies, including muscle loss, gastrointestinal side effects, treatment discontinuation, and weight regain after therapy ends. With IND-enabling studies progressing, the company plans to advance RV-8451 into Phase 1 clinical development for obesity following its anticipated IND submission in early 2027.
Expanding Rivus’ Cardiometabolic Pipeline
RV-8451 complements Rivus Pharmaceuticals’ broader cardiometabolic portfolio, which includes HU6, an oral therapy currently being evaluated in the Phase 2 AMPLIFY trial for metabolic dysfunction-associated steatohepatitis (MASH). By focusing on therapies that improve energy expenditure and body composition, Rivus aims to develop next-generation treatments that provide sustainable cardiometabolic benefits beyond traditional weight-loss approaches.
Source: Rivus Pharmaceuticals press release
