Madrigal Pharmaceuticals Triples Q4 Revenue as Rezdiffra Adoption Accelerates

Madrigal Pharmaceuticals (MDGL) has solidified its position as the dominant force in the metabolic dysfunction-associated steatohepatitis (MASH) market, following a fourth-quarter performance that saw revenue more than triple year-over-year. The company reported net sales of $321.1 million for the quarter, bringing its full-year 2025 total to $958.4 million. This milestone marks the first full year of commercial availability for Rezdiffra (resmetirom), the first and only FDA-approved treatment for MASH with liver fibrosis. The rapid adoption of Rezdiffra is evidenced by a significant jump in the patient base, which grew from 29,500 in the third quarter to over 36,250 by the end of 2025. This sequential growth of nearly 23% highlights the strong clinical demand and the effectiveness of Madrigal’s commercial execution in a previously underserved therapeutic area.

Despite the impressive top-line growth, Madrigal management signaled a shift in financial dynamics for 2026 that investors are watching closely. The company’s gross-to-net (GTN) discount, which averaged in the low 20% to 30% range during 2025, is expected to climb into the high 30% range in the coming year. This adjustment is primarily driven by new, broad-based payer agreements designed to secure long-term access and volume. While a higher GTN discount typically puts pressure on per-patient revenue, Madrigal’s strategy prioritizes market penetration and long-term persistence. Currently, the company reports a one-year persistence rate of 60% to 70%, with some high-performing institutions reaching as high as 90%. Maintaining these rates will be critical as the company transitions from early adopters to a broader patient demographic.

“

This includes a $120 million upfront payment for an oral GLP-1 asset and a $50 million investment in a late-stage DGAT-2 inhibitor and six preclinical siRNA assets.

Beyond its flagship product, Madrigal is aggressively diversifying its portfolio to become a multi-modality metabolic powerhouse. The company’s R&D spending reflects this ambition, totaling $388.5 million for the year. This includes a $120 million upfront payment for an oral GLP-1 asset and a $50 million investment in a late-stage DGAT-2 inhibitor and six preclinical siRNA assets. By integrating these diverse technologies—specifically combining the direct liver-acting benefits of Rezdiffra with the systemic metabolic benefits of GLP-1s—Madrigal aims to create a comprehensive treatment ecosystem for MASH and related metabolic disorders. This pipeline expansion is a strategic hedge against future competition and a clear signal that the company intends to lead the next generation of metabolic medicine.