Madrigal Pharmaceuticals (NASDAQ:MDGL) highlighted a near-$1 billion first full year of net sales for Rezdiffra during its fourth quarter and full year 2025 earnings call, while emphasizing accelerating diagnosed patient growth in the U.S. MASH market and a broadened R&D pipeline built around combination strategies.
Rezdiffra launch: nearly $1 billion in first full year net sales
Chief Executive Officer Bill Sibold said the company ended its first full year on the market with $958 million in net sales, describing Rezdiffra as “the foundational therapy in MASH.” Fourth quarter 2025 net sales were $321 million, which management said was more than triple the prior-year quarter.
Patient growth and market expansion in U.S. MASH
Management said patient growth continued through the fourth quarter. The company reported ending the quarter with more than 36,250 patients on Rezdiffra, up from more than 29,500 at the end of the third quarter. Sibold noted the patient figure reflects the net of new starts and discontinuations.
On the call, executives emphasized that the U.S. MASH market is expanding rapidly. Sibold said the F2/F3 target population of representative patients seen by the company’s target specialists has expanded by nearly 50% since the end of 2023, and he expects the market to grow at a double-digit pace for the foreseeable future. In response to questions, Sibold pointed to increasing awareness and diagnosis, along with broader industry efforts that are bringing more patients into the care pathway.
Asked about the types of patients starting therapy and prescriber dynamics, Sibold said the mix remains “pretty even” between F2 and F3, with prescriptions “mostly in the hep GI space,” and more gastroenterologists than endocrinologists. He described the next phase as going deeper into existing prescribers’ patient populations as Rezdiffra becomes standard of care.
Expanding into compensated MASH cirrhosis (F4c) and outcomes focus
Sibold and Chief Medical Officer David Soergel discussed the company’s strategy to expand into compensated MASH cirrhosis (F4c), which management said could represent approximately 245,000 patients and could “double” the commercial opportunity if approved. The company highlighted that its F4c trial is focused on clinically meaningful outcomes—preventing decompensation—rather than relying on biopsy.
Soergel said the company’s confidence in its outcomes approach is supported by data from a two-year open-label study in compensated cirrhosis patients from the NAFLD-1 trial. He described clinically significant portal hypertension (CSPH) as a key inflection point in cirrhosis progression, and said that in the 122-patient dataset, 65% of patients with CSPH at baseline moved into lower-risk categories by year two.
On the MAESTRO outcomes study timeline, Soergel said event rates are tracking within expected ranges, referencing historical natural history data of roughly 5%–10% annual event accrual in cirrhosis. Management reiterated an expectation to deliver outcomes data in 2027, while noting it is too early to provide more precise timing guidance.
Pipeline strategy: combination therapies anchored by Rezdiffra
Soergel said Madrigal’s R&D objective is to build an “industry-leading pipeline in MASH,” with four stated goals:
- Deliver outcomes data and full approval for Rezdiffra from F2 through F4c
- Advance complementary mechanisms for combination with Rezdiffra
- Remain modality agnostic (including injectable approaches)
- Design “smarter” and more informative clinical trials using Madrigal’s MASH experience
Management said the company has moved from a single-asset launch story to a pipeline that is now “more than 10 programs” deep, supported by business development activity. Executives highlighted three recent additions intended for combination use with Rezdiffra: an oral GLP-1 candidate, a late-stage DGAT2 inhibitor (ervogastat), and six preclinical siRNA targets. The company said Rezdiffra’s patent exclusivity has been extended to 2045.
On DGAT2 inhibition, Soergel described the mechanistic rationale as complementary to THR-beta agonism, with DGAT2 inhibition addressing triglyceride production while resmetirom supports mitochondrial function and fat clearance through beta oxidation. He said ervogastat has completed a Phase 2B trial in MASH with robust MRI-PDFF reductions and “clean safety,” citing MYRNA study results where 72% of patients at 150 mg achieved at least a 30% PDFF reduction and 61% achieved a 50% reduction. Madrigal plans to initiate a drug-drug interaction study in 2026 and expects to begin a Phase 2 combination program in 2027 following FDA discussions.
On the oral GLP-1 program (MGL-2086), management said there is “strong real-world enthusiasm” for combining GLP-1s with resmetirom due to mechanistic complementarity. Soergel said the company is targeting a once-daily oral fixed-dose combination aimed at optimizing MASH efficacy and tolerability rather than “maximal weight loss,” noting that MAESTRO-NASH data suggested as little as 5% weight loss meaningfully potentiated Rezdiffra’s fibrosis benefit. A Phase 1 single-ascending dose study of MGL-2086 is expected to start in the second quarter.
Regarding siRNA, executives said they will not disclose the specific targets for competitive reasons, but described the modality as liver-targeted (GalNAc conjugation) with a safety profile supported by multiple marketed products. They characterized the potential regimen as a long-acting injection (every 3–6 months) alongside a daily pill. Soergel added that FDA interest in qualifying non-invasive tests (NITs) is increasing and said NITs are expected to play a major role in assessing combination programs in Phase 2, while acknowledging FDA discussions will shape study design.
2026 outlook: contracting, gross-to-net, and expenses
Chief Financial Officer Mardi Dier said Madrigal expects a “step-up” in gross-to-net in 2026 due to payer contracting. She said the full-year 2025 gross-to-net result came in at the low end of the company’s previously discussed 20%–30% range, while full-year 2026 is expected to be in the high 30% range, consistent with specialty medicine analogs. Dier said the company expects gross-to-net to remain generally in the high 30s across 2026 quarters, with normal variability.
Management said payer agreements were in place as of January 1 and that the company achieved broad first-line access with no step edits. Executives also discussed typical first-quarter dynamics, including benefit plan changes and insurance re-verifications, noting specialty analogs often see a mid- to high-single-digit net sales decline in Q1, and that 2026’s Q1 will also reflect the impact of moving from minimal contracting to broader contracting.
On operating expenses, Madrigal reported:
- R&D expenses: $116.3 million in Q4 2025 and $388.5 million for full-year 2025, with increases primarily tied to business development upfront payments
- SG&A expenses: $240 million in Q4 2025 and $813.8 million for full-year 2025, reflecting launch support
Dier said the company expects 2026 R&D expenses to be roughly in line with 2025, while SG&A is expected to increase as Madrigal continues to support the Rezdiffra launch and build for long-term growth.
The company ended the fourth quarter with $988.6 million in cash, cash equivalents, restricted cash, and marketable securities, which management said leaves it well resourced to support the ongoing launch, pipeline advancement, and continued business development.
On international rollout, management said Germany’s contribution to 2025 results was “negligible,” and it does not expect significant ex-U.S. contribution in 2026, describing the U.S. as the base business for near-term growth.
About Madrigal Pharmaceuticals (NASDAQ:MDGL)
Madrigal Pharmaceuticals, Inc is a clinical-stage biopharmaceutical company focused on the development of innovative therapies for cardiovascular, metabolic and liver diseases. The company’s pipeline centers on novel, liver-directed agents designed to address significant unmet medical needs, with an emphasis on nonalcoholic steatohepatitis (NASH) and related metabolic disorders.
The lead product candidate, resmetirom (MGL-3196), is an orally administered, selective thyroid hormone receptor-β agonist in Phase 3 development for the treatment of NASH.
