Dual efficacy: Rezdiffra delivers statistically significant fibrosis improvement* and steatohepatitis resolution† at Week 521

There were no differences in response to Rezdiffra for both primary endpoints based on age, gender, type 2 diabetes status, GLP‑1 therapy, or fibrosis stage (F2 or F3)1,2

Fibrosis improvement with no worsening of steatohepatitis

  Placebo
(n=294)		 Rezdiffra 80 mg
(n=298)		 Rezdiffra 100 mg
(n=296)
Response rate,
Pathologist A (%) 		15 23 28
Difference in response rate vs placebo (95% CI)   8 (2, 14) 13 (7, 20)
Response rate,
Pathologist B (%) 		13 23 24
Difference in response rate vs placebo (95% CI)   11 (5, 17) 11 (5, 17)

Rezdiffra achieved statistically significant results for fibrosis improvement for both doses in a statistical analysis incorporating both pathologists' independent readings.1,‡

Fibrosis improvement combined analysis Fibrosis improvement combined analysis
Fibrosis improvement paired biopsy imputed analysis Fibrosis improvement paired biopsy imputed analysis
Paired Biopsy/Imputed Analysis Details

In MAESTRO-NASH, patients without a Week 52 liver biopsy were considered an “endpoint non-responder” in the primary endpoint analysis for the intent-to-treat population (N=888).1 Given these “endpoint non-responders” were each randomized to a treatment group and could have potentially responded, the FDA conducted an independent sensitivity analysis, imputing all missing values with a logistic regression model, which adjusted for treatment group, baseline type 2 diabetes (presence or absence), baseline fibrosis stage (F2 or F3), and pathologist.4 Based on Madrigal data, 695 (78.3% of the 888) patients had paired biopsy data at both baseline and Week 52 (n=246, placebo; n=234, 80 mg; n=215, 100 mg), resulting in 193 (21.7%) patients without paired biopsy data (n=48, placebo; n=64, 80 mg; n=81, 100 mg).3

*Fibrosis improvement: ≥1-stage improvement in fibrosis with no worsening of steatohepatitis (defined as no increase in score for ballooning, inflammation, or steatosis).1

Steatohepatitis resolution with no worsening of fibrosis

  Placebo
(n=294)		 Rezdiffra 80 mg
(n=298)		 Rezdiffra 100 mg
(n=296)
Response rate,
Pathologist A (%) 		13 27 36
Difference in response rate vs placebo (95% CI)   14 (8, 20) 23 (16, 30)
Response rate,
Pathologist B (%) 		9 26 24
Difference in response rate vs placebo (95% CI)   17 (11, 23) 15 (9, 21)

Rezdiffra achieved statistically significant results for steatohepatitis resolution for both doses in a statistical analysis incorporating both pathologists’ independent readings.1,‡

Steatohepatitis resolution combined analysis Steatohepatitis resolution combined analysis
Steatohepatitis resolution paired biopsy imputed analysis Steatohepatitis resolution paired biopsy imputed analysis
Paired Biopsy/Imputed Analysis Details

In MAESTRO-NASH, patients without a Week 52 liver biopsy were considered an “endpoint non-responder” in the primary endpoint analysis for the intent-to-treat population (N=888).1 Given these “endpoint non-responders” were each randomized to a treatment group and could have potentially responded, the FDA conducted an independent sensitivity analysis, imputing all missing values with a logistic regression model, which adjusted for treatment group, baseline type 2 diabetes (presence or absence), baseline fibrosis stage (F2 or F3), and pathologist.4 Based on Madrigal data, 695 (78.3% of the 888) patients had paired biopsy data at both baseline and Week 52 (n=246, placebo; n=234, 80 mg; n=215, 100 mg), resulting in 193 (21.7%) patients without paired biopsy data (n=48, placebo; n=64, 80 mg; n=81, 100 mg).3

†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.1
‡Patients with missing liver biopsy at Week 52 were considered non-responders.1
§Combined pathologist results estimated using the Mantel-Haenszel method stratified by baseline type 2 diabetes status (presence or absence) and fibrosis stage (F2 or F3).2
Learn more about the MAESTRO-NASH trial design.

Learn how to identify appropriate patients for Rezdiffra

See Characteristics

Learn about the demonstrated safety and tolerability profile of Rezdiffra1

See Safety Information
GLP-1=glucagon-like peptide-1; MASH=metabolic dysfunction-associated steatohepatitis, formerly known as NASH or nonalcoholic steatohepatitis.
References:
  1. Rezdiffra. Prescribing Information. Madrigal Pharmaceuticals, Inc.
  2. Harrison SA et al. N Engl J Med. 2024;390(6)(article and suppl):497-509.
  3. Data on file. REF-00630. Madrigal Pharmaceuticals, Inc.; June 2024.
  4. Data on file. REF-00923. Madrigal Pharmaceuticals, Inc.; November 2024.