More than 42,250 patients were taking Rezdiffra as of March 31, roughly two and a half times the count from a year earlier. That growth curve has carried Madrigal Pharmaceuticals from a single-drug launch story into a company now spending its early revenue on the next stage of its pipeline.
Filling an Empty Shelf
Rezdiffra, known chemically as resmetirom, became the first medicine the FDA ever approved for metabolic dysfunction-associated steatohepatitis when it received accelerated approval in March 2024. MASH scars the liver through fat accumulation and inflammation and can progress to cirrhosis, liver failure or the need for a transplant; before Rezdiffra, doctors had no approved drug to reach for and were left steering patients toward weight loss and tighter control of conditions such as diabetes that make the disease worse.
The approval rested on the Phase 3 MAESTRO-NASH trial, which enrolled 1,759 patients and found that both the 80 mg and 100 mg doses of Rezdiffra improved liver fibrosis and resolved MASH at significantly higher rates than placebo after 52 weeks. Stephen Harrison, the trial’s lead investigator and a visiting professor of hepatology at Oxford University, called it “a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition” in Madrigal’s approval announcement.
At the time of approval, Madrigal estimated that roughly 1.5 million people in the U.S. had been diagnosed with MASH, with about 525,000 of them in the moderate-to-advanced fibrosis range the drug targets. Two years later, the company puts the diagnosed pool eligible for treatment at closer to 460,000 patients, a figure it attributes to wider screening and rising disease awareness rather than a change in how many people actually have the condition.
The Ramp
Two years into the launch, the commercial numbers have moved past most single-product biotech debuts. First-quarter 2026 net sales reached $311.3 million, up 127% from $137.3 million in the same period of 2025. Trailing-12-month sales have now cleared $1.1 billion, a threshold that Madrigal’s chief executive, Bill Sibold, described as “blockbuster status” in the company’s first-quarter release. The addressable population is expanding alongside it: Sibold pointed to a MASH market that has grown nearly 50% to roughly 460,000 diagnosed patients in just two years.
The expense side of the ledger grew too. Operating expenses reached $404.1 million for the quarter, including $54.3 million in one-time business development costs tied to a pipeline acquisition, up from $216.6 million a year earlier. Selling, general and administrative costs alone rose to $268.5 million from $167.9 million, largely on an expanded endocrinology sales force and a new direct-to-consumer advertising push, the kind of spending a company makes when it believes a market still has room to grow rather than one trying to protect a shrinking franchise. Madrigal posted a net loss of $94.4 million, or $3.25 per share, narrower on a per-share basis than the $4.14 Wall Street had modeled, though wider in dollar terms than the $73.2 million loss in the prior-year quarter. Cash, equivalents and marketable securities stood at $817.9 million as of March 31, down from $988.6 million at the end of 2025.
A Harder Population to Treat
Rezdiffra’s approved label covers patients with moderate to advanced fibrosis who have not yet reached cirrhosis. The larger prize sits one stage further along the disease, in patients with compensated MASH cirrhosis, where the Phase 3 MAESTRO-NASH-OUTCOMES trial is testing whether the drug prevents liver decompensation events before damage becomes irreversible. A positive readout would open Rezdiffra to a sicker population than the one it treats today, though outcomes trials of this kind typically run for years before generating the kind of data regulators require.
At the European Association for the Study of the Liver’s EASL Congress in Barcelona in late May, Madrigal presented eight posters, including a two-year analysis of that cirrhosis population showing improvement in ANTICIPATE-NASH scores, a marker doctors use to gauge the risk of clinically significant portal hypertension, a dangerous complication of advanced liver scarring. A separate analysis drawn from the MAESTRO-NASH and MAESTRO-NAFLD-1 trials found that Rezdiffra lowered Lp(a), LDL cholesterol and ApoB, lipid markers tied to cardiovascular risk, independent of whether patients were already taking statins. David Soergel, Madrigal’s chief medical officer, said the data “extend beyond liver-focused assessments to explore Rezdiffra’s effects on markers of cardiovascular risk.”
Two Bets on What Comes After a Pill
Madrigal is not relying on Rezdiffra alone to carry the pipeline forward. On May 5, the company licensed global rights to ARO-PNPLA3 from Arrowhead Pharmaceuticals for a $25 million upfront payment, with Arrowhead eligible for up to $975 million in development, regulatory and sales milestones plus tiered royalties. ARO-PNPLA3 is a small interfering RNA candidate aimed at a gene mutation that drives fibrosis progression in roughly 30% of MASH patients with F2 to F3 disease; in a 55-patient Phase 1 trial where 93% of participants were Hispanic or Latino, a single dose produced up to a 46% reduction in liver fat within 12 weeks among patients carrying two copies of the mutation.
A second gene-silencing bet followed in July. Suzhou Ribo Life Science and its Swedish subsidiary Ribocure Pharmaceuticals cleared the first milestone under a separate siRNA agreement with Madrigal, a nomination event that moves the program into IND-enabling work, the animal and manufacturing studies required before human dosing can begin. “Madrigal has established a market leading presence and profound clinical expertise in the MASH field, while Ribo possesses world-class capabilities in siRNA drug discovery and delivery technology,” said Li-Ming Gan, Ribo’s co-chief executive and global head of research and development, in the companies’ joint announcement.
Neither deal will contribute revenue for years. Both are preclinical or early clinical, both rely on gene-silencing technology Madrigal did not develop in-house, and both are aimed at working alongside Rezdiffra rather than replacing it. Taken together with the six earlier-stage siRNA programs Madrigal added in February, the two agreements suggest a company using its early Rezdiffra cash flow to buy optionality in a disease area it already dominates rather than leaving that cash on the balance sheet.
Who Owns the Stock
Madrigal’s shareholder base splits fairly cleanly by size and mandate. Specialist biotech investors hold the largest stakes: Baker Bros. Advisors reported 2,141,701 shares worth roughly $982 million as of its most recent 13F, RTW Investments held 1,993,687 shares worth about $914 million, and Avoro Capital Advisors held 1,833,000 shares worth roughly $841 million. Index managers Vanguard, BlackRock and State Street appear further down the ownership table, tracking the stock through broad funds rather than concentrated conviction bets.
Hedge funds occupy a different tier entirely. Armistice Capital‘s most recent 13F showed 119,982 shares worth about $55 million, a position roughly one-eighteenth the size of Baker Bros.’ stake, alongside a separate holding of 130,000 call option contracts worth around $60 million, meaning the options exposure was actually larger than the equity position itself. Armistice has paired equity with derivatives in other health-care names in its portfolio, including a call-option position layered on top of its Cytokinetics equity stake, a structure that lets a fund participate in a stock’s upside without tying up the capital a comparably sized equity position would require. Janus Henderson and Paulson & Co. also rank among Madrigal’s disclosed institutional holders, filling out a registry of 658 institutions that collectively report holding more than 26.8 million shares, a figure that runs above Madrigal’s roughly 23 million shares outstanding once index funds and the underlying funds that mirror them are both counted in fintel.io’s data.
Where the Stock Sits Now
Madrigal shares traded near $555 in late July, up from a 52-week low of $286.44 and within range of the 52-week high of $615. The stock’s market capitalization has grown to roughly $12.8 billion. Wall Street has moved price targets higher through the year: Wells Fargo initiated coverage with an Overweight rating and an $685 target, citing more than $7 billion in potential peak Rezdiffra sales, while Truist and Citizens have both raised their targets since Madrigal’s first-quarter report. The average 12-month analyst target sits around $680, roughly 23% above the recent trading price, according to data compiled by StockAnalysis.com. Madrigal is due to report second-quarter results on July 30, which will show whether the patient-growth trend held through the spring or whether the pace set in the first quarter was a temporary spike tied to pent-up demand from a first-in-disease launch. None of this constitutes investment advice, and a company still years from its next major trial readout carries risks that a rising share price does not erase.