Rezdiffra was evaluated in MAESTRO-NASH: a comprehensive Phase 3 trial in noncirrhotic MASH patients with moderate to advanced fibrosis1,2

MAESTRO-NASH is an ongoing Phase 3, randomized, double-blind, placebo-controlled trial. Efficacy and safety were evaluated in 888 adults with biopsy-confirmed MASH with stage F2 or F3 liver fibrosis (at eligibility).1

Trial design schema for MAESTRO-NASH

Efficacy1

Week 52 dual primary endpoints

  • Fibrosis improvement: ≥1-stage improvement in fibrosis with no worsening of steatohepatitis (defined as no increase in score for ballooning, inflammation, or steatosis)*
  • Steatohepatitis resolution: Resolution of steatohepatitis (score of 0-1 for inflammation, 0 for ballooning, and any value for steatosis) with no worsening of liver fibrosis
  • Pathologist A and Pathologist B independently read the liver biopsies for each patient
  • Patients with missing liver biopsy at Week 52 were considered non-responders in the primary analysis

Stratification1

  • Patients were stratified by baseline type 2 diabetes status (present/absent) and fibrosis stage (F2 or F3)

Key inclusion and exclusion criteria1,2

Inclusion

  • ≥18 years of age
  • Presence of ≥3 metabolic risk factors†
  • Liver biopsy confirmed fibrosis stage: F2 or F3‡
  • NAS ≥4
  • VCTE ≥8.5 kPa; CAP ≥280 dB/m§
  • MRI-PDFF ≥8%||

Exclusion

  • Moderate to severe hepatic impairment (Child-Pugh B or C)
  • Cirrhosis
  • Liver decompensation
  • Chronic liver diseases, autoimmune hepatitis, hepatocellular carcinoma
  • History of significant alcohol consumption#
  • Platelet count <140,000/mm3
  • MELD score ≥12**

Learn how to identify appropriate patients for Rezdiffra

See Characteristics
*Liver fibrosis was evaluated on the NASH Clinical Research Network (CRN) fibrosis score as 0 to 4.1
†Includes obesity, type 2 diabetes, dyslipidemia, and hypertension.2
‡If a patient had a biopsy ≤6 months before enrollment, it was considered a qualifying biopsy.2
§For patients with a historic liver biopsy <2 years old, baseline VCTE and CAP could be <8.5 kPa and <280 dB/m, respectively.2
||CAP ≥280 dB/m was allowed if MRI-PDFF was unavailable.2
Primary biliary cholangitis, primary sclerosing cholangitis, hepatitis B, hepatitis C.2
#History of significant alcohol consumption for more than 3 consecutive months within 1 year prior to screening. Significant alcohol consumption is defined as equal to or greater than approximately 2 alcoholic drinks per day for males, and approximately 1.5 alcoholic drinks per day for females.2
**As determined at screening, unless due to therapeutic anti-coagulation.2
AR=adverse reaction; CAP=controlled attenuation parameter; dB/m=decibels per meter; kPa=kilopascal; MASH=metabolic dysfunction-associated steatohepatitis, formerly known as NASH or nonalcoholic steatohepatitis; MELD=Model for end-stage liver disease; MRI-PDFF=magnetic resonance imaging proton density fat fraction; NAS=nonalcoholic fatty liver disease (NAFLD) activity score; NIT=noninvasive test; VCTE=vibration‑controlled transient elastography.
References:
  1. Rezdiffra. Prescribing Information. Madrigal Pharmaceuticals, Inc.
  2. Harrison SA et al. N Engl J Med. 2024;390(6):497-509 (article, suppl, and protocol).