Rivus Pharmaceuticals, a biopharma company focused on therapies for cardiometabolic health, announced positive data from their Phase IIa clinical trial Wednesday morning. Rivus’s experimental drug, HU6, showed significant fat reduction and weight loss in patients struggling with obesity. The success rate was significant, but the unique way in which the patients lost weight was what made this clinical trial stand out.
The Charlottesville, Virginia-based company was founded with the mission to create controlled metabolic accelerators, a new class of medicines that treat the underlying metabolic causes of type 2 diabetes, HFpEF and NASH, along with other cardiovascular and metabolic diseases.
These medicines boost patients’ metabolisms to help them burn fat. The drug, HU6, was tested in a double-blind, placebo-controlled trial of 80 people, all of whom had a body mass index between 28 and 45 with an elevated liver fat of at least 8%. Patients received doses of 150 mg, 300 mg, 450 mg, or a placebo. Strikingly, statistically significant weight loss and liver fat reduction were seen across all dosage groups—with no changes to diet or exercise.
The primary differentiator here is that the weight loss came exclusively from fat loss, with no loss of lean muscle mass. Additionally, the fat loss was even greater in patients who were more obese. In an interview with BioSpace, Rivus Chief Executive Officer Allen Cunningham and Chief Scientific Officer Shaharyar Khan, Ph.D., explained the significance of that finding.
“No other mechanism has been able to selectively target fat loss instead of muscle loss. When other weight loss therapies induce a caloric deficit, a lot of the weight loss in most patients is lean muscle mass. Anywhere from 20 to 60% of the weight loss is skeletal muscle and lean body mass, but that’s not what we see with this clinical trial. We see strictly fat loss. And in patients who had especially elevated A1C levels [high blood glucose levels], we see even greater fat loss,” Khan said.
The fact that the drug showed increased benefit with extremely obese patients is impressive. The patients who struggle most with obesity may be at a point where diet and exercise is not a quick enough solution.
“Many of these patients are exercise-intolerant. It’s harder to achieve fat loss when you have a metabolic disorder or diabetes or elevated HbA1c [blood hemoglobin and glucose] levels,” Cunningham explained. “The patients may not be capable of addressing the root cause of their obesity disease. This HU6 drug works with the metabolism to help them get them to a point where they can exercise because they’re at a healthier weight.”
Because the study subjects strictly lost fat, without losing muscle mass, they saw improvements in other areas of their health.
“We’re also seeing lower glycemic indexes in this study. About 40% of the patients in the study had elevated A1C, meaning they were diabetic or pre-diabetic. We’re seeing improvements in glycemic control, significant reductions in liver fat, histological improvements, and reductions in high-sensitivity CRP, which is a marker of systemic inflammation and cardiovascular risk—all while preserving muscle mass,” Khan said. “We’re watching this drug help people not only do better but feel better.”
This clinical trial was also unique because of the focus on safety. Both Cunningham and Khan made it clear in the interview that safety had been a priority during all planning and execution stages of the study – and that safety showed in the results. There were no serious adverse events reported during the study. Also, the drug showed excellent tolerability.
Going forward, the Rivus team is excited for the potential that HU6 holds for vulnerable patients struggling with obesity. They’re also intrigued by the data the study has offered into understanding how and why HU6 is so effective.
“The exciting thing about this Phase II data is that it gives us visibility into the effects that we’ll see by indication and by dose in metabolic diseases. One thing that has been really helpful from this study is our understanding of how this drug works and our ability to select the proper dosage. This is the groundwork for further clinical development that will be required for specific indications,” Cunningham shared.
As Rivus continues innovating, it plans to hold a Phase IIb clinical trial exclusively in patients with type 2 diabetes. The company also plans to file for an Investigational New Drug (IDE) application for HU6 with the U.S. Food and Drug Administration’s Division of Cardiology and Nephrology in Q1 2022.