Rivus Pharmaceuticals Initiates Phase II AMPLIFY Trial for HU6 in MASH Treatment
核心洞察
Rivus Pharmaceuticals (搜索) has dosed the first patients in the AMPLIFY Phase II trial evaluating HU6, an investigational oral therapy for metabolic dysfunction-associated steatohepatitis (搜索) (MASH (搜索)).
The randomized, double-blind, placebo-controlled trial will enroll up to 180 adults with F2/F3 MASH (搜索) to assess HU6's potential to reduce liver fat and preserve muscle mass.
Previous M-ACCEL Phase II trial data showed that the majority of patients achieved greater than 30% liver fat reduction, a clinically meaningful outcome associated with MASH (搜索) resolution.
Rivus Pharmaceuticals (搜索) has initiated dosing of the first patients in the AMPLIFY Phase II clinical trial, marking a significant milestone in the development of HU6, an investigational oral therapy for metabolic dysfunction-associated steatohepatitis (搜索) (MASH (搜索)). The trial represents a critical step forward in addressing the substantial unmet medical need for effective MASH treatments.
Trial Design and Patient Population
The AMPLIFY trial is a randomized, double-blind, placebo-controlled Phase II study that will enroll approximately 180 adults with F2/F3 MASH (搜索). Participants will be randomized in a 2:1:2:1 ratio to receive either HU6 at 450mg daily, 300mg twice daily, or placebo for six months. The study design allows for comprehensive evaluation of HU6's safety, tolerability, and efficacy across different dosing regimens.
The primary efficacy endpoint focuses on change in liver fat as measured by MRI-proton density fat fraction (MRI-PDFF) and the proportion of patients achieving greater than 30% reduction in liver fat at six months. Key secondary outcomes include changes in body composition and weight, liver fibrosis measures, metabolic and inflammatory markers, and pharmacodynamic parameters.
Building on Promising Phase II Data
The AMPLIFY trial builds upon encouraging results from the M-ACCEL Phase II trial, which were presented as a late-breaker oral presentation at the 2025 American Association for the Study of Liver Diseases (AASLD) Liver Meeting. The M-ACCEL data demonstrated robust liver-centric effects with significant reductions in liver fat across 228 patients at the six-month endpoint.
Notably, the majority of patients in the M-ACCEL trial achieved more than 30% reduction in liver fat, a target that has been shown to be a clinically meaningful outcome associated with MASH (搜索) resolution and fibrosis improvement. The therapy also demonstrated fat-selective weight loss with preservation of skeletal muscle mass, along with a favorable safety and tolerability profile.
Clinical Development Progress
HU6 has been administered to more than 500 patients across clinical studies to date, consistently demonstrating favorable safety and tolerability alongside improvements in cardiometabolic risk markers. The therapy's development program has generated publications in prestigious journals including The Lancet Gastroenterology & Hepatology and JAMA Cardiology.
Following the initial six-month double-blind period in AMPLIFY, patients will be eligible to continue in an open-label extension for an additional six months, providing longer-term safety and efficacy data.
Addressing MASH Disease Burden
MASH (搜索), formerly known as nonalcoholic steatohepatitis (搜索) (NASH (搜索)), affects approximately 5% of U.S. adults and represents a serious, chronic liver disease characterized by excess fat accumulation in the liver leading to inflammation and scarring. Left untreated, MASH can progress to cirrhosis (搜索), liver failure (搜索), hepatocellular carcinoma (搜索), and premature death. The condition is rapidly becoming the leading cause of liver transplantation, though diagnosis and treatment rates remain low.
The disease serves as an independent driver of cardiovascular disease (搜索), which represents the leading cause of mortality for MASH (搜索) patients, highlighting the critical connection between hepatic and systemic cardiometabolic health.
Commercial Timeline and Strategic Planning
Jorge Bartolome, Chief Executive Officer of Rivus Pharmaceuticals (搜索), emphasized the significance of this clinical milestone: "We are excited to dose the first patients in our AMPLIFY Phase II trial, marking an important clinical milestone for HU6's development for MASH (搜索). AMPLIFY builds on the positive data from our M-ACCEL trial, showing HU6's best-in-class potential as an oral MASH therapy with robust liver-centric effects and unique fat-selective, muscle-preserving weight loss."
Top-line data from the AMPLIFY trial is anticipated in mid-2027, which will inform dosing strategies for planned late-stage clinical trials. The company is actively planning for HU6's late-stage development and potential commercialization, positioning itself with a platform focused on increasing energy expenditure to deliver improved and sustained cardiometabolic health.