After several quarters on a steady sales roll as the world’s first treatment for metabolic dysfunction-associated steatohepatitis (MASH), the pressure is on for Madrigal Pharmaceuticals’ Rezdiffra thanks to the arrival of a new MASH competitor.
In Madrigal’s fourth-quarter and full-year earnings report, the company looked to clear up a key question: Can Madrigal’s sole commercialized product hold its own against Novo Nordisk’s blockbuster GLP-1 Wegovy, which was recently endorsed in MASH?
With Rezdiffra’s $958.4 million in 2025 sales and more than 36,250 patients on the therapy as of year-end, CEO Bill Sibold is confident that the answer is yes.
“Rezdiffra is performing exceptionally well,” Sibold emphasized on the company’s earnings conference call Thursday. “This is truly [the] best launch I’ve ever been associated with, and I can tell you that is from a factual perspective—nothing’s done as well as this, and it’s poised for substantial long-term growth in a rapidly growing market.”
That’s quite the eye-opening claim considering Sibold was once part of the launch team for Sanofi and Regeneron’s immunology powerhouse Dupixent, which is now generating megablockbuster sales.
For evidence of Rezdiffra’s strength, the executive pointed to the prescription volume growth the drug has seen on a quarterly level, including the climb from the 29,500 patients who were on the therapy as of the third quarter of 2025, according to a Madrigal presentation (PDF). So far, the company has only penetrated about 12% of the 315,000-patient target market that it figures can be captured under Rezdiffra’s label for MASH with moderate or severe fibrosis consistent with stage F2 and F3 disease, according to the document.
Despite the company’s enthusiasm for the launch, investors apparently expected more. While sales impressed Wall Street analysts, Madrigal’s loss for the period came worse than expected. Shares were down about 8% Thursday afternoon.
Even if Rezdiffra is “the foundational therapy” in MASH, in Madrigal’s own words, it can’t foster a multibillion-dollar market all on its own. The company, in its presentation, pointed to other large therapeutic categories, such as psoriasis and inflammatory bowel disease, which were boosted by an onslaught of approved therapies over time.
This is where Novo comes in, as Madrigal sees it. After tacking on a MASH nod as its third FDA indication last summer, Wegovy’s push into the market has aided Madrigal on the patient-awareness side, Sibold said.
Although the executive noted that Novo may need “lots of patience in order to make MASH a meaningful indication for them,” Wegovy’s impact in the space is “certainly not to the detriment of Rezdiffra.” Sibold pointed to Rezdiffra’s recent best new-to-brand prescription (NBRx) week since launch as indicative that “you can have multiple products in the space, but that Rezdiffra really is the winning profile.”
Over the fourth quarter specifically, the drug generated $321.1 million in sales, up from $103.3 million during 2024’s fourth quarter and $287 million in 2025’s third quarter. The first quarter of 2026 may see a decline in net sales around the mid-to-high single-digit percentage range, a “typical” Q1 impact that chief financial officer Mardi Dier explained takes into account seasonal factors but shouldn’t detract from the “robust sales growth” expected in 2026.
Analysts at Evercore ISI agreed that those first-quarter hurdles shouldn’t be cause for alarm, explaining that “[p]atient count can increase while revenue dips if patients miss one or two doses during plan transitions,” citing typical insurance reauthorizations that occur in the first months of the new year.
“That dynamic, combined with contracting phasing, explains the optics without implying a demand issue,” the Evercore team said.
Meanwhile, Madrigal is looking to expand beyond its current status as a one-product company with an “industry-leading MASH pipeline” full of differentiated assets and combination programs that could “transform patient care,” according to the company’s presentation.
The pipeline setup is “deliberate” to suit better patient outcomes across a wide MASH population for the long-term, Sibold said.
“We are seven quarters into the launch of an entirely new category. There are decades of growth and evolution in front of us,” he said. “The decisions that we’re making today with the pipeline aren’t 2026 decisions.”
Beyond Rezdiffra’s potential within different combination treatments, the company looks to add another 245,000 patients to the drug’s addressable population with an indication in compensated MASH cirrhosis, or stage F4 liver scarring. Madrigal is running a phase 3 trial in the indication, with data expected in 2027, and says it expects to be the first to market in this patient population.
“We have a chance to build long-term leadership,” Sibold said. “It doesn't happen often. This is an opportunity. We are not going to waste the opportunity.”