Among patients with elevated Lp(a) who were already on statins, resmetirom drove 37.5% of those starting above 50 mg/dL below that threshold — a clinically meaningful shift, because statins do essentially nothing for Lp(a). That single figure reframes what Rezdiffra’s cardiovascular signal actually means. This isn’t a drug that happens to lower lipids alongside liver endpoints; it’s addressing a lipoprotein fraction that standard-of-care cardiology systematically ignores.
The secondary analysis from MAESTRO-NASH and MAESTRO-NAFLD-1 covering roughly 966 patients on 100 mg resmetirom shows LDL and Lp(a) reductions that held regardless of whether patients were already statin-treated. In the statin-naive group, 62.5% of those with baseline Lp(a) ≥50 mg/dL crossed below that threshold by week 52. That is a striking magnitude, and it raises a legitimate question about trial design: future cardiovascular outcomes studies in MASH will need to account for Lp(a) as a prespecified stratification variable, not an afterthought. The MASH field has spent years debating whether liver endpoints are surrogate enough; the cardiovascular co-benefit data are now strong enough to demand a dedicated MACE endpoint.
Separately, the ANTICIPATE-NASH analysis in 180 cirrhosis patients treated for up to two years is arguably the more consequential data set for regulatory purposes. Patients with F4c MASH have no approved therapy, and Madrigal is constructing a noninvasive risk-stratification argument using portal hypertension probability scores as a bridge to hard outcomes. The proportion classified as high-risk for clinically significant portal hypertension fell from 75% at baseline to 54.5% at year two — a 20-point shift — and liver-related events occurred only in patients who started with elevated ANTICIPATE-NASH scores. That pattern gives the scoring tool prospective utility, not just descriptive value. It also hands Madrigal a potential registration-enabling framework for the cirrhosis indication that doesn’t require waiting for decompensation events.
The real-world data showing 49% of patients achieving ≥25% reduction in liver stiffness over nine months matters less for label expansion than for payer dynamics — it gives medical directors a reason not to restrict access pending longer-term outcomes data. The single number to track from here is the proportion of F4c patients in the OLE cohort who sustain ANTICIPATE-NASH score reductions past year two, since that trajectory will define whether Madrigal files for the cirrhosis indication on biomarker grounds alone.
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.
