Forty-nine percent of MASH patients in real-world practice achieved a 25% or greater reduction in liver stiffness within nine months of starting resmetirom — a figure that matters because liver stiffness is the surrogate most clinicians actually use to make treatment decisions, not the histologic endpoints that anchor phase 3 trials. That gap between trial endpoints and clinical monitoring tools has always been the quiet vulnerability in resmetirom’s post-approval story, and Madrigal is systematically closing it with a dataset that now spans eight posters at EASL 2026.
The more strategically important numbers come from the MAESTRO cardiovascular secondary analysis. Among statin-naive patients on resmetirom 100mg, 62.5% of those with baseline Lp(a) at or above 50 mg/dL dropped below that threshold by week 52. Statins do not meaningfully move Lp(a) — that is not a matter of debate. Resmetirom’s thyroid receptor beta agonism does, and the effect held regardless of whether patients were already on a statin. That finding reframes resmetirom from a pure liver drug into something that competes on cardiovascular risk reduction without requiring a separate mechanism or a separate pill. It also creates a clinical rationale for prescribing it in MASH patients whose hepatologists would not traditionally think hard about Lp(a).
The F4c cirrhosis data deserve equal attention. Resmetirom has no approved indication in decompensated or high-risk compensated cirrhosis, yet this population is exactly where liver-related mortality concentrates. The ANTICIPATE-NASH analysis from the MAESTRO-NAFLD-1 open-label extension shows the proportion of patients classified as high-risk for clinically significant portal hypertension fell from 75% at baseline to 54.5% at year two, with liver-related events occurring exclusively in patients who started with elevated ANTICIPATE-NASH scores. That is not a validated surrogate endpoint — it is a risk stratification model applied post hoc — but it generates the biological signal needed to justify a prospective F4c trial with hard outcomes.
The single marker worth tracking here is Lp(a) response in the forthcoming cardiovascular outcomes study design. If Madrigal constructs an outcomes trial that includes Lp(a) as a pre-specified secondary endpoint in statin-naive MASH patients, the drug’s commercial ceiling expands well beyond hepatology — directly into cardiology referral patterns.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
