Third quarter 2026 earnings call, November 3, 2026

A second F4c outcomes trial changes the shape of the cirrhosis program

The most consequential new disclosure on Madrigal's third quarter call was MAESTRO-CSPH, a second Phase III outcomes trial in compensated cirrhosis (F4c) MASH. The company plans to enroll more than 2,000 patients, enriched for clinically significant portal hypertension (CSPH), and to start the study in the first half of 2027 after finalizing the protocol with the FDA. Results are expected in the early 2030s. Combined with the ongoing 845-patient MAESTRO-NASH OUTCOMES study, the F4c program would total roughly 3,000 patients.

Management framed the trial as a defensive and commercial move as much as a scientific one. CEO Bill Sibold described it as "a leapfrog study" intended to "raise the bar for the entire industry." He argued that many companies wait until after approval to generate data and end up "in a bit of a data desert" playing "continuous catch-up." Madrigal wants "no daylight" between its first F4c approval and any competitor's launch. Chief Medical Officer Dave Soergel said the design draws on 5 years of experience in MAESTRO-NASH OUTCOMES, the 2-year open-label F4c cohort in MAESTRO-NAFLD-1, and newer tools for identifying CSPH, including the Baveno consensus criteria and ANTICIPATE-NASH scores.

The logic of two outcomes trials is that the first can be mined for biomarkers, imaging measures and subpopulations that predict benefit, and the second can validate them. That would give prescribers practical guidance on whom to treat and how to monitor them. Management said it intends the trial to be fully represented in the product label, but the FDA discussions on this point are still ahead. Soergel also acknowledged a risk inherent in enriching for sicker patients, noting that patients can be "too far along in the CSPH journey" to be treated effectively, so the company is trying to find the "sweet spot" within CSPH. Management declined to give enrichment specifics, calling them a competitive advantage, and did not offer event-rate assumptions for the new study.

MAESTRO-NASH OUTCOMES narrows to late 2027, with no guarantee

Madrigal tightened the readout timing for MAESTRO-NASH OUTCOMES from "2027" to "late 2027." Management declined to give blinded event accrual figures, saying trials of this size are "choppy," and said dropout rates are within expectations. Several analysts pressed on whether a slip into 2028 is possible. Sibold did not rule it out, saying the trial is event-driven and "if we're at December 31, 2027, and we don't have the right number of events, we're just not going to stop the study."

On the placebo event rate, Soergel defended the company's 5% to 10% assumption against analyst concerns that controlled studies have shown rates closer to 2% to 3%. He argued that F4c is "not a monolithic disease" and that the trial was enriched for the more advanced end of the cirrhosis spectrum. Background GLP-1 use is a further variable. About 25% to 30% of patients were on stable GLP-1 therapy at baseline, and adding one during the study would be a protocol deviation.

Management also said a positive result would support both a new F4c indication and full approval across F2 through F4c, consistent with FDA guidance. On competition, Sibold said rivals have modified programs, enlarged studies and pushed timelines, with the earliest potential F4c entrant now not expected until 2030. Madrigal also raised its estimate of addressable US F4c patients to 360,000 from 245,000, an increase of more than 45%. Management says that is larger than the F2-F3 population at Rezdiffra's launch and that F4c could double the franchise opportunity.

Rezdiffra sales reach $431 million and the company posts its first profit

Third quarter net sales were $431.3 million, up 50% year over year. Year-to-date sales passed $1 billion and the quarterly run rate is above $1.7 billion. Active patients reached more than 55,850, versus more than 29,500 a year earlier. Madrigal reported its first profitable quarter, with net income of $55.4 million against a net loss of $114.2 million a year ago. The year-ago loss included $117.3 million of one-time upfront business development expense in R&D. The company has been operating cash flow positive for two quarters and ended September with $961.8 million in cash.

The profit should not be read as a durable trend. CFO Mardi Dier said the company remains "a top-line growth story" and "may dip in and out of profitability in the near term." SG&A was $265.7 million, up from $209.1 million, and is expected to be higher in the fourth quarter. Management also pointed to seasonal first-quarter weakness similar to that of other specialty drugs. Cost of sales rose to $37.8 million from $18.1 million, driven mainly by higher royalties to Roche. Full-year R&D is expected to be nominally lower than in 2025, and full-year SG&A higher.

Gross-to-net and 2027 commentary

Madrigal expects 2026 gross-to-net deductions at the low end of its mid- to high-30s percentage range. Medicare Part D contracts, now under negotiation, take effect in the first quarter of 2027, and the company expects gross-to-net to be "plus or minus the high end" of the mid- to high-30s range next year. That implies some pricing pressure, though management said the big step-up occurred between 2025 and 2026 with commercial contracting.

The company is not issuing 2027 guidance. Dier said she is comfortable with consensus, but she warned about first-quarter seasonality. For the fourth quarter, management reiterated comfort with the consensus sequential growth rate. Sibold said "mega-blockbuster" is a moving target but that current consensus peak estimates qualify.

Market growth is accelerating, and Wegovy has not dented demand

Madrigal estimates the diagnosed US F2-F3 MASH population at more than 530,000 as of June 30, up from 460,000 at the end of 2025 and 315,000 at the end of 2023. It is on track to grow more than 30% in 2026. Diagnosis is still only about 10%, and Rezdiffra penetration of the diagnosed population is also about 10%, which Sibold summarized as being "about 1% into the total opportunity." That framing is generous, since it assumes the undiagnosed population is ultimately treatable, but diagnosed-market growth is the data point that supports it.

Sibold said that after five quarters of competition from Novo Nordisk's Wegovy in MASH, "it hasn't really dented us," and he argued it has helped expand the market. About 25% of Rezdiffra patients are on a GLP-1, a share that has moved up only slightly. Endocrinology, which the company began calling on in the fourth quarter of 2025, is still early, though Sibold said endocrinologists who convert "go deeper, faster."

Combination pipeline: three Phase II starts in 2027

Madrigal now counts more than 10 resmetirom combination programs and plans three Phase II combination trials in 2027, subject to regulatory discussions. The first pairs the oral DGAT-2 inhibitor ervogastat with resmetirom, following a Phase I drug-drug interaction study begun in October. The second pairs the oral GLP-1 agonist MGL-2086 with resmetirom once the Phase I SAD/MAD study is complete. Soergel said the aim is to "dial in the right amount of weight loss" to enhance the antifibrotic effect while preserving tolerability. The third pairs MGL-0795, an siRNA targeting PNPLA3, with resmetirom in patients homozygous for the disease-accelerating mutation. Earlier-stage work includes 6 siRNA programs and 3 exploratory assets.

The company will present 13 real-world data abstracts at AASLD this week, the largest covering nearly 12,000 patients. It is also running practice-informing studies of Rezdiffra with pioglitazone and with an SGLT-2 inhibitor. Two-year open-label F4c data showed 65% of patients with baseline CSPH moving to a lower risk category. That is encouraging but uncontrolled evidence, from only 122 patients.

Patent protection for Rezdiffra is expected into 2045, and management says the nearest competitor in F2-F3 is at least 15 quarters behind.