Rivus Pharmaceuticals Begins Dosing First Patients In AMPLIFY Phase 2 Trial For HU6, Its Promising Oral MASH Therapy

Rivus Pharmaceuticals Inc., a clinical-stage biopharmaceutical company focused on advancing cardiometabolic health, announced that the first patients have been dosed in the AMPLIFY Phase 2 clinical trial evaluating HU6, its investigational oral therapy being developed as a potential best-in-class treatment for MASH.

According to Jorge Bartolome, Chief Executive Officer of Rivus Pharmaceuticals, dosing the first patients represents an important step in the clinical development of HU6. He noted that the AMPLIFY study builds on encouraging results from the earlier M-ACCEL trial, which demonstrated strong liver-focused effects, meaningful reductions in liver fat, fat-selective weight loss, and preservation of muscle mass. With top-line AMPLIFY data expected in mid-2027, the company is preparing for HU6’s late-stage development and potential future commercialization.

The AMPLIFY Phase 2 trial is a randomized, double-blind, placebo-controlled study designed to evaluate HU6 in adults diagnosed with F2/F3 MASH (metabolic dysfunction-associated steatohepatitis). The study plans to enroll up to 180 participants who will be assigned in a 2:1:2:1 ratio to receive HU6 at either 450 mg once daily or 300 mg twice daily, compared with placebo, over a treatment period of six months. The study aims to assess safety, drug exposure, and efficacy.

The primary objective of the trial is to measure the change in liver fat using MRI-PDFF and to determine the percentage of patients achieving more than a 30% reduction in liver fat after six months of treatment. Secondary objectives include evaluating changes in body composition and body weight, liver fibrosis markers, metabolic and inflammatory parameters, and pharmacodynamic outcomes. Participants will have the option to continue treatment in a six-month open-label extension. The trial is registered under ClinicalTrials.gov: NCT07491458.

The AMPLIFY study follows the positive results from the M-ACCEL Phase 2 trial, which were presented as a late-breaker oral presentation at the 2025 AASLD Liver Meeting. In that study, which included 228 patients over six months, HU6 demonstrated significant liver-centric effects, with the majority of patients experiencing reductions of more than 30% in liver fat. This level of improvement is clinically meaningful and closely associated with MASH resolution and improvements in liver fibrosis. The trial also showed fat-selective weight loss, preservation of skeletal muscle mass, and a favorable safety and tolerability profile, supporting HU6 as a promising long-term therapy option for individuals living with MASH.

MASH, formerly known as NASH, is a serious and chronic liver disease caused by the buildup of excess fat in the liver. This accumulation leads to inflammation and scarring, which can progress to cirrhosis, liver failure, hepatocellular carcinoma, and the need for liver transplantation. MASH is also closely linked to cardiovascular disease, which is the leading cause of death in affected patients, highlighting the strong relationship between liver health and overall cardiometabolic health. Despite affecting an estimated 5% of adults in the United States, MASH remains underdiagnosed and undertreated. As rates of metabolic diseases continue to rise globally, the health burden associated with MASH is expected to increase significantly.

HU6 is Rivus Pharmaceuticals’ lead investigational therapy and is being developed as a potential best-in-class oral treatment for MASH, a condition with limited therapeutic options and a significant unmet medical need. In previous Phase 2 trials, HU6 demonstrated strong liver-centric effects, fat-selective and muscle-preserving weight loss, and improvements in markers associated with cardiovascular risk. 

More than 500 patients have been treated with HU6 to date, and the therapy has continued to show a favorable safety and tolerability profile. Clinical results for HU6 have been published in leading medical journals, including The Lancet Gastroenterology & Hepatology and JAMA Cardiology, and have been presented at major scientific meetings such as the AASLD Liver Meeting.