Madrigal’s Rezdiffra Surpasses $950M in 2025 as Pipeline Expands into GLP-1s

Madrigal Pharmaceuticals has officially transitioned from a clinical-stage pioneer to a commercial heavyweight in the metabolic dysfunction-associated steatohepatitis (MASH) space. The fourth quarter of 2025 saw net sales of $321.1 million, a figure that more than triples the previous year's performance. This trajectory brought full-year revenue to $958.4 million, narrowly missing the billion-dollar milestone in Rezdiffra’s first full year of availability. The patient base grew to over 36,250 by year-end, representing a robust sequential increase from the 29,500 reported in the third quarter. This growth underscores the high unmet need in the liver disease market and Madrigal's successful execution of its launch strategy.

However, the commercial landscape for Rezdiffra is entering a more complex phase. While Madrigal enjoyed favorable gross-to-net (GTN) discounts in the low 20% to 30% range throughout 2025, management has signaled a shift toward the high 30% range for 2026. This adjustment is a direct result of broader payer agreements aimed at securing preferred formulary positions and expanding access. While this may pressure margins in the short term, it is a necessary tactical move to maintain the volume growth required to dominate the MASH sector before competitors arrive. The company’s persistence rates—a critical metric for chronic oral therapies—remain steady at 60% to 70% at the one-year mark, with some high-performing institutions reaching as high as 90%, suggesting strong patient adherence to the daily oral regimen.

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The company spent $388.5 million on R&D in 2025, which included a $120 million upfront payment for an oral GLP-1 and $50 million for a DGAT-2 inhibitor.

Beyond the immediate success of Rezdiffra, Madrigal is making significant R&D investments to diversify its portfolio. The company spent $388.5 million on R&D in 2025, which included a $120 million upfront payment for an oral GLP-1 and $50 million for a DGAT-2 inhibitor. This strategic expansion indicates that Madrigal does not intend to remain a single-product company. By securing six preclinical siRNA assets in the latter half of the year, the company is positioning itself at the intersection of small molecule and genetic medicine. The integration of an oral GLP-1 is particularly noteworthy, as it allows Madrigal to compete in the broader obesity and metabolic syndrome market, potentially offering combination therapies with Rezdiffra to address both liver health and weight management.