Madrigal Pharmaceuticals Inc. (Nasdaq: MDGL) generated $958.4 million in net sales from Rezdiffra (resmetirom) across fiscal year 2025, the drug’s first full year on the commercial market following its March 2024 FDA approval as the first and only approved therapy for metabolic dysfunction-associated steatohepatitis with moderate to advanced liver fibrosis
Armistice Capital was among the institutional investors holding or expanding positions in the company during 2025. Baker Bros. Advisors, RTW Investments, Vanguard Group, BlackRock, Wellington Management Group, and Paulson & Co. are other institutional holders of record.
A Launch Measured in Quarters
The Rezdiffra commercial trajectory is most legible quarter by quarter. Madrigal recorded $137.3 million in net revenues in the first quarter of 2025, the first full quarter with a complete sales infrastructure in place. By the second quarter, demand had accelerated as payer coverage expanded and physician familiarity with the drug’s prescribing label grew. Third-quarter net revenues annualized above $1 billion, and the fourth quarter closed at $321.1 million, more than triple the $103.3 million posted in the fourth quarter of 2024
The patient base tracked the revenue curve. Madrigal reported more than 17,000 patients on Rezdiffra at the end of the first quarter 2025. That figure reached 29,500 by the third quarter and exceeded 36,250 by year-end, growth of more than 100% over the course of the year. More than 10,000 healthcare providers had written at least one prescription for Rezdiffra by the end of the third quarter.
Full-year operating expenses reached $1.26 billion, driven primarily by $813.8 million in selling, general, and administrative costs tied to launch infrastructure, and $388.5 million in research and development expenditures — the latter reflecting substantial upfront payments for pipeline licensing transactions.
The Disease and Its Scale
MASH is a progressive liver disease defined by fat accumulation, inflammation, and hepatocellular injury. It develops within the broader category of metabolic dysfunction-associated steatotic liver disease (MASLD), the renamed successor to nonalcoholic fatty liver disease, a nomenclature update adopted in 2023 by professional liver disease organizations to reduce stigma and more precisely describe the metabolic drivers of the condition. Approximately 22 million adults in the United States are estimated to have MASH. Of those, roughly 315,000 patients with moderate to advanced fibrosis, classified as F2 to F3 on the standard fibrosis staging scale, are under the care of liver specialists and represent Rezdiffra’s currently approved patient population.
MASH that progresses to fibrosis carries significant mortality risk. Patients with F2 to F3 fibrosis face a 10 to 17 times higher risk of liver-related mortality compared to those without fibrosis; those who reach cirrhosis face a 42 times higher risk.
MASH is currently the leading cause of liver transplantation among women in the United States and the second leading cause overall.
One modeling study published in JAMA projected the population with MASH and clinically significant fibrosis would grow 75%, from 6.7 million in 2020 to 11.7 million by 2050, highlighting the rapid expansion of the MASH drug market, with MASH cirrhosis cases nearly doubling over the same period.
Rezdiffra’s Mechanism and Market Position
Resmetirom, the active compound in Rezdiffra, is a once-daily, oral thyroid hormone receptor-beta (THR-β) agonist designed to act directly on liver tissue. THR-β activation in hepatocytes reduces fat accumulation and improves several metabolic markers associated with MASH drug market progression. The drug’s approval was based on results from the pivotal Phase 3 MAESTRO-NASH trial, which demonstrated statistically significant MASH drug market resolution and fibrosis improvement without worsening. The FDA granted accelerated approval on the basis of histological endpoints in March 2024; the European Commission followed with conditional marketing authorization in August 2025, after which Madrigal launched Rezdiffra commercially in Germany in September 2025.
A new U.S. patent listed in the FDA’s Orange Book in August 2025 extends Rezdiffra’s patent protection to 2045, covering the commercial weight-threshold dosing regimen specified in the approved label.
Despite Rezdiffra’s sole-approved status in the category, the competitive pipeline is active. Novo Nordisk has sought regulatory approval for semaglutide as a MASH treatment. Akero Therapeutics reported Phase 3 data for efruxifermin, showing cirrhosis reversal in 39% of treated patients versus 15% in the placebo group. Viking Therapeutics’ VK2809 showed fibrosis improvement in Phase 2b trials. Several additional candidates, including efimosfermin alfa, icosabutate, and denifanstat, are in mid-to-late development. Madrigal’s position as the first approved therapy gives it a significant payer coverage and prescriber-familiarity advantage, but it is developing combination strategies specifically to maintain that position as additional approvals arrive.
Madrigal’s Pipeline
Madrigal’s spending trajectory in 2025 reflected a deliberate shift from a single-product company to a pipeline-driven one. Three transactions during the year added candidates designed for future combination use with Rezdiffra as the foundational agent.
An oral GLP-1 receptor agonist, designated MGL-2086 — an orforglipron derivative licensed in September 2025 — is expected to enter clinical trials in the second quarter of 2026. A separate exclusive global license for ervogastat, a Phase 2 DGAT-2 inhibitor, was announced in the fourth quarter. Phase 2 data for ervogastat showed 72% of patients achieved at least a 30% reduction in liver fat and 61% achieved at least a 50% reduction. Madrigal plans a drug-to-drug interaction study with Rezdiffra and FDA consultation on a Phase 2 combination trial design in 2026. A third deal, announced in February 2026, licensed global rights to six preclinical siRNA programs, which target gene silencing as a complementary mechanism to Rezdiffra’s receptor-based approach.
The company’s most consequential near-term clinical milestone is the ongoing Phase 3 MAESTRO-NASH OUTCOMES trial, which is evaluating Rezdiffra in compensated MASH cirrhosis — fibrosis stage F4c — a population of approximately 245,000 patients under specialist care in the U.S. Topline data are expected in 2027. Two-year open-label extension data presented at major liver disease meetings in 2025 showed that 65% of F4c patients with clinically significant portal hypertension at baseline moved into lower risk categories by year two, results that management cited as consistent with the baseline characteristics of patients enrolled in the OUTCOMES trial, underscoring momentum in the MASH drug market.
Institutional Positioning and Analyst Coverage
Madrigal became one of Armistice Capital’s top equity holdings by the end of Q4 2025, per the firm’s 13F filing dated Feb. 17, 2026. Lord, Abbett & Co. added shares over the same period. Larger, longer-standing institutional holders include Baker Bros. Advisors, RTW Investments, Vanguard Group, Avoro Capital Advisors, Paulson & Co., BlackRock, Janus Henderson Group, State Street Corp., Wellington Management Group, and Geode Capital Management. Institutional investors hold approximately 98.5% of Madrigal shares outstanding.
Wall Street analyst coverage has been uniformly constructive. Nine firms carried buy ratings on MDGL as of early 2026, with no sell ratings reported. The median analyst price target across 11 firms was $640, with B. Riley Securities setting a target of $670 and HC Wainwright among the other bullish voices.
For 2026, management guided for continued robust net sales growth, while cautioning that gross-to-net dynamics — the spread between list price and net realized revenue after payer rebates and contracting — would shift into the high-30% range as broader formulary contracting takes effect. That step-up, typical of specialty medicines in their second and third years post-launch, will pressure reported revenue growth rates relative to the underlying demand trajectory.
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