Madrigal Pharmaceuticals Reports Fourth-Quarter and Full-Year 2024 Financial Results and Announces New Two-Year Data Demonstrating Potential Benefit of Rezdiffra™ (resmetirom) in Patients with Compensated MASH Cirrhosis

Rhea-AI Summary

Madrigal Pharmaceuticals (NASDAQ:MDGL) reported strong Q4 and full-year 2024 results for Rezdiffra™, the first FDA-approved MASH treatment. Q4 net sales reached $103.3 million, contributing to full-year sales of $180.1 million. The company ended 2024 with $931.3 million in cash and equivalents.

New two-year data from the Phase 3 MAESTRO-NAFLD-1 trial showed promising results for patients with compensated MASH cirrhosis, including a mean 6.7 kPa reduction in liver stiffness, with 51% of patients achieving ≥25% reduction. These results support Rezdiffra's potential benefit in cirrhosis patients.

Key 2024 milestones included FDA approval in March, commercial launch in April, and recognition in updated EASL and AASLD guidelines as first-line therapy. The company completed enrollment in the MAESTRO-NASH OUTCOMES trial, with data expected in 2027. European expansion is planned for H2 2025, pending EMA approval.

Positive

• Strong Q4 sales of $103.3M and FY2024 sales of $180.1M
• Robust cash position of $931.3M
• Positive two-year trial data showing significant liver improvement
• 11,800+ patients on Rezdiffra by year-end
• First-line therapy recommendation in EASL and AASLD guidelines
• Potential European market expansion in H2 2025

Negative

• Operating expenses increased to $678M from $380.5M YoY
• SG&A expenses surged to $435.1M from $108.1M YoY
• MAESTRO-NASH OUTCOMES trial results not expected until 2027

Insights

Financial Analyst

Madrigal Pharmaceuticals delivered strong commercial momentum in its first year of Rezdiffra sales, reporting $103.3 million in Q4 and $180.1 million for full-year 2024. These results are particularly impressive considering the April 2024 launch, representing just 9 months of commercialization for the first-ever FDA-approved MASH treatment. With over 11,800 patients now on therapy, Madrigal has demonstrated significant early adoption in this previously untreated market affecting an estimated 6-8 million Americans with F2-F3 MASH fibrosis.

The company's robust $931.3 million cash position provides substantial runway to support continued commercialization efforts and clinical development, despite elevated operating expenses of $678 million for 2024. The 303% year-over-year increase in SG&A expenses to $435.1 million reflects the substantial investment in building commercial infrastructure and launch activities, which should provide operating leverage as sales continue to scale.

The newly announced two-year data in compensated MASH cirrhosis patients represents a potential growth catalyst by expanding Rezdiffra's addressable market. The mean 6.7 kPa reduction in liver stiffness is clinically meaningful, as a ≥25% reduction (achieved by 51% of patients) has been associated with reduced progression to end-stage liver disease. This data strengthens the potential for positive outcomes in the ongoing MAESTRO-NASH OUTCOMES trial in F4c patients, results expected in 2027.

European expansion represents another significant growth opportunity, with potential EMA approval in mid-2025 and initial launch in Germany in H2 2025. The updated treatment guidelines from both EASL and AASLD recommending Rezdiffra as first-line therapy should accelerate adoption both domestically and internationally.

Madrigal has established a commanding first-mover advantage in the MASH treatment landscape. While several competitors have pipeline candidates, none are expected to reach market before 2026-2027, giving Rezdiffra a substantial window to establish market leadership in this high-value therapeutic area.

Healthcare Specialist

The newly announced two-year data for Rezdiffra in compensated MASH cirrhosis represents a significant clinical advancement with important implications for the most severe subset of MASH patients. The mean 6.7 kPa reduction in liver stiffness is remarkable in this difficult-to-treat population, as cirrhotic tissue has historically been considered less responsive to therapeutic intervention due to extensive scarring and architectural distortion.

What makes this finding particularly meaningful is that 51% of patients achieved a ≥25% reduction in liver stiffness - a threshold associated with reduced progression to clinical events in published research. For context, patients with compensated cirrhosis face annual risks of 2-7% for developing decompensation events (ascites, variceal bleeding, encephalopathy) that dramatically increase mortality risk and lead to liver transplant evaluation.

The consistency of these improvements at the two-year mark suggests Rezdiffra may provide sustained benefit in modifying the natural history of MASH cirrhosis, potentially delaying or preventing progression to decompensation. This represents a paradigm shift in our approach to advanced MASH, as current management is largely focused on monitoring for complications rather than disease modification.

These data provide compelling support for the ongoing MAESTRO-NASH OUTCOMES trial in F4c patients, which will measure hard clinical endpoints including progression to decompensation, transplant, and mortality. The strong VCTE signal increases confidence in the potential success of this pivotal trial, expected to read out in 2027.

For clinicians treating MASH patients, these results offer preliminary evidence that Rezdiffra's mechanisms of action - addressing both metabolic dysfunction and inflammation through thyroid hormone receptor-β agonism - remain effective even in advanced fibrotic disease. While the current FDA label is to F2-F3 MASH, these data may influence clinical decision-making for high-risk compensated cirrhosis patients who currently have no approved therapeutic options.

If the OUTCOMES trial confirms these findings with hard clinical endpoints, Rezdiffra would become the first agent to demonstrate benefit across the full spectrum of fibrotic MASH (F2-F4c), solidifying Madrigal's leadership position in this rapidly evolving therapeutic area.

• Fourth-quarter and full-year 2024 Rezdiffra net sales of $103.3 million and $180.1 million, respectively
• As of year-end 2024, more than 11,800 patients on Rezdiffra
• Reports cash, cash equivalents, restricted cash and marketable securities of $931.3 million at December 31, 2024
• Announces new two-year data for the active-treatment open-label compensated MASH cirrhosis (F4c) arm of the Phase 3 MAESTRO-NAFLD-1 trial
• Company to host conference call today, February 26, 2025, at 8 a.m. EST
  

CONSHOHOCKEN, Pa., Feb. 26, 2025 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), today reports fourth-quarter and year-end 2024 financial results and reviews business highlights.

Bill Sibold, Chief Executive Officer of Madrigal, stated, “Looking back on 2024, I’m incredibly proud of what we accomplished. We secured FDA approval for Rezdiffra, the first medicine approved for MASH, in March; executed a first-in-disease launch with remarkable results; and are well positioned for strong performance again in 2025 and beyond.”

Sibold continued, “The U.S. launch of Rezdiffra has energized the MASH community, and we’re positioned to extend our leadership. Today, we’re sharing new two-year analyses from an active-treatment open-label extension arm of our Phase 3 MAESTRO-NAFLD-1 trial that demonstrate Rezdiffra continues to improve key markers of MASH fibrosis out to two years in patients with compensated MASH cirrhosis (F4c). These results add to the growing body of evidence supporting Rezdiffra’s potential benefit in this high-risk patient population, for which there is no approved therapy. A positive read out in our fully enrolled Phase 3 MAESTRO-NASH OUTCOMES trial could make Rezdiffra the first and only treatment for F2 to F4c MASH, and the only therapy with outcomes data this decade.”

New Two-Year Data from the Active-Treatment Open-Label Compensated MASH Cirrhosis Arm of the Rezdiffra Phase 3 MAESTRO-NAFLD-1 Trial

• MAESTRO-NAFLD-1 was a double-blind placebo-controlled, randomized Phase 3 safety trial conducted to support regulatory approval of Rezdiffra. The trial includes an active-treatment open-label extension arm in patients with compensated MASH cirrhosis. Madrigal previously reported one-year results for this active treatment arm.
• Today, the Company is announcing, two-year results (n=101):
  • The patient cohort achieved a mean 6.7 kPa reduction in liver stiffness as measured by vibration-controlled transient elastography (VCTE); this represents the largest VCTE reduction reported in an F4c MASH patient population to date. This reduction was statistically significant as compared to baseline.
  • 51% of patients achieved a ≥ 25% reduction in liver stiffness as measured by VCTE. A reduction of this magnitude has been associated with reduced progression to end-stage liver disease.
  • Rezdiffra’s safety and tolerability profile was consistent with other Rezdiffra clinical trials with a low discontinuation rate due to adverse events.
• Madrigal plans to present these data and additional findings from the active-treatment open-label cirrhosis arm of the MAESTRO-NAFLD-1 trial at a future medical meeting.
• The results further support the potential benefit of Rezdiffra in patients with compensated MASH cirrhosis and the potential success of the ongoing MAESTRO-NASH OUTCOMES trial, a double blind, placebo-controlled, event-driven trial in F4c, for which data are anticipated in 2027.
  

2024 Highlights

• Landmark FDA approval of Rezdiffra
  • In February 2024, Rezdiffra Phase 3 MAESTRO-NASH trial 52-week results were published in The New England Journal of Medicine; the paper was subsequently chosen as one of the journal’s 14 notable scientific research articles of 2024.
  • In March 2024, Madrigal announced FDA approval of Rezdiffra for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).
  • In April 2024, Rezdiffra became commercially available as the first and only approved therapy for MASH.
• Expert guidelines recommend Rezdiffra as first-line therapy for MASH
  • In June 2024, the European Association for the Study of the Liver (EASL) Congress updated their practice guidelines to recommend Rezdiffra as a first-line therapy for MASH, subject to regulatory approval in Europe.
  • In October 2024, the American Association for the Study of Liver Diseases (AASLD), a leading organization of scientists and health care professionals committed to preventing and curing liver disease, updated their practice guidelines to recommend Rezdiffra as a first-line therapy for MASH and implemented recommendations regarding its use for clinicians.
• Driving future growth through European expansion
  • In March 2024, Madrigal announced that the marketing authorization application (MAA) for resmetirom for the treatment of MASH with liver fibrosis was validated and is under evaluation with the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP). The CHMP opinion and subsequent European Union (EU) decision is expected in mid-2025.
  • Madrigal expects to launch Rezdiffra in Europe on a country-by-country basis commencing with Germany in the second half of 2025, pending EMA approval, which would make it the first approved therapy for patients with MASH liver fibrosis in Europe.
• Driving future growth through indication expansion
  • In October 2024, Madrigal announced completion of enrollment in the MAESTRO-NASH OUTCOMES trial, an event-driven trial evaluating Rezdiffra in patients with F4c, an advanced and underserved patient population. Positive results could position Rezdiffra to become the only treatment for F2 to F4c MASH and the only therapy with outcomes data in MASH this decade.
• Strong presence at key liver meetings
  • In June 2024, Madrigal presented 10 abstracts at the EASL congress, including noninvasive test (NIT) data that demonstrated 91% of patients achieved improvement or stabilization of liver stiffness out to three years.
  • In November 2024, Madrigal had a significant presence at the AASLD Liver Meeting. Eleven Madrigal abstracts were presented at the meeting, including two oral presentations of new analyses from the Phase 3 MAESTRO-NASH trial of Rezdiffra.
    

Fourth-Quarter and Full-Year 2024 Financial Results

• Total revenues: The Company generated fourth-quarter and full-year 2024 net revenues of $103.3 million and $180.1 million, respectively. No product sales were recognized during the comparable prior year period.
• Operating Expenses: Fourth-quarter and full-year 2024 operating expenses were $170.3 million and $678.0 million, respectively, compared to $117.2 million and $380.5 million in the comparable prior year periods.
  • Cost of sales: Fourth-quarter and full-year 2024 cost of sales were $3.4 million and $6.2 million, respectively. Cost of sales were not recognized during the comparable prior year periods given that no product sales were recorded.
  • R&D Expense: Fourth-quarter and full-year 2024 R&D expense was $25.6 million and $236.7 million, respectively, compared to $70.6 million and $272.4 million in the comparable prior year periods. Research and development expenses decreased by $35.6 million in 2024 due primarily to a reduction in clinical trial accruals and the change in accounting for inventory costs following FDA approval of Rezdiffra in March 2024, partially offset by increases in headcount.
  • SG&A Expense: Fourth-quarter and full-year 2024 SG&A expense was $141.2 million and $435.1 million, respectively, compared to $46.5 million and $108.1 million in the comparable prior year periods. Selling, general and administrative expenses increased by $326.9 million in 2024 due primarily to increases for commercial launch activities for Rezdiffra, including a corresponding increase in headcount, and an increase in stock compensation expense.
• Interest Income: Fourth-quarter and full-year 2024 interest income was $11.1 million and $46.7 million, respectively, compared to $9.0 million and $19.6 million in the comparable prior year periods. The increase in interest income was due primarily to higher principal balances and interest rates in 2024.
• Interest Expense: Fourth-quarter and full-year 2024 interest expense was $3.5 million and $14.7 million, respectively, compared to $4.0 million and $12.7 million in the comparable prior year periods. The increase in interest expense in 2024 was primarily the result of a higher average outstanding principal balance during the period under the Madrigal’s loan facility.
• Cash, Cash Equivalents, Restricted Cash and Marketable Securities: As of December 31, 2024, Madrigal had cash, cash equivalents, restricted cash and marketable securities of $931.3 million, compared to $634.1 million at December 31, 2023. This increase was primarily attributable to the $659.9 million of net proceeds we received from our underwritten public offering in March 2024.

Conference Call and Webcast
At 8 a.m. EST today, February 26, 2025, Madrigal will host a webcast to review its financial and operating results and provide a general business update. To access the webcast, please visit the investor relations section of the Madrigal website or click here to register. An archived webcast will be available on the Madrigal website following the event.

About MASH
Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), is a serious liver disease that can progress to cirrhosis, liver failure, liver cancer, need for liver transplantation, and premature mortality. MASH is expected to become the leading cause of liver transplantation in the U.S. and is already the leading cause of liver transplantation among women.

Once patients progress to MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis), the risk of adverse liver outcomes increases dramatically: these patients have a 10-17 times higher risk of liver-related mortality as compared to patients without fibrosis. Those who progress to cirrhosis face a 42 times higher risk of liver-related mortality, underscoring the need to treat MASH before complications of cirrhosis develop. MASH is also an independent driver of cardiovascular disease, the leading cause of mortality for patients.

An estimated 1.5 million patients have been diagnosed with MASH in the U.S., and Madrigal is focused on reaching approximately 315,000 patients with moderate to advanced fibrosis who are under the care of liver specialists. As MASH disease awareness improves and disease prevalence increases, the number of diagnosed patients with MASH with moderate to advanced fibrosis is expected to grow.

About Rezdiffra
What is Rezdiffra?
Rezdiffra is a prescribed medicine used along with diet and exercise to treat adults with nonalcoholic steatohepatitis (NASH) with moderate to advanced liver scarring (fibrosis), but not with cirrhosis of the liver.
It is not known if Rezdiffra is safe and effective in children (under 18 years old).
This indication is approved based on improvement of NASH and liver scarring (fibrosis). There are ongoing studies to confirm the clinical benefit of Rezdiffra.
Before you take Rezdiffra, tell your healthcare provider about all of your medical conditions, including if you:

• have any liver problems other than NASH.
• have gallbladder problems or have been told you have gallbladder problems, including gallstones.
• are pregnant or plan to become pregnant. It is not known if Rezdiffra will harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if Rezdiffra passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Rezdiffra.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

• Rezdiffra and other medicines may affect each other, causing side effects. Rezdiffra may affect the way other medicines work, and other medicines may affect how Rezdiffra works.
• Especially tell your healthcare provider if you take medicines that contain gemfibrozil to help lower your triglycerides, or cyclosporine to suppress your immune system, because Rezdiffra is not recommended in patients taking these medicines.
• Tell your healthcare provider if you are taking medicines such as clopidogrel to thin your blood or statin medicines to help lower your cholesterol.
• Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

What are the possible side effects of Rezdiffra?
Rezdiffra may cause serious side effects, including:

• liver injury (hepatotoxicity). Stop taking Rezdiffra and call your healthcare provider right away if you develop the following signs or symptoms of hepatotoxicity: tiredness, nausea, vomiting, fever, rash, your skin or the white part of your eyes turns yellow (jaundice), pain or tenderness in the upper middle or upper right area of your stomach (abdomen).
• gallbladder problems. Gallbladder problems such as gallstones, inflammation of the gallbladder, or inflammation of the pancreas from gallstones can occur with NASH and may occur if you take Rezdiffra. Call your healthcare provider right away if you develop any signs or symptoms of these conditions including nausea, vomiting, fever, or pain in your stomach area (abdomen) that is severe and will not go away. The pain may be felt going from your abdomen to your back and the pain may happen with or without vomiting.

The most common side effects of Rezdiffra include: diarrhea, nausea, itching, stomach (abdominal) pain, vomiting, dizziness, constipation.
These are not all the possible side effects of Rezdiffra. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Madrigal at 1-800-905-0324.
Please see the full Prescribing Information, including Patient Information, for Rezdiffra.

About Madrigal
Madrigal Pharmaceuticals, Inc. (Nasdaq: MDGL) is a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), a liver disease with high unmet medical need. Madrigal’s medication, Rezdiffra (resmetirom), is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of MASH. Rezdiffra is the first and only medication approved by the FDA for the treatment of MASH with moderate to advanced fibrosis (consistent with stages F2 to F3). An ongoing Phase 3 outcomes trial is evaluating Rezdiffra for the treatment of compensated MASH cirrhosis (consistent with stage F4c). For more information, visit www.madrigalpharma.com.

Forward Looking Statements
This press release includes “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended, including statements related to the launch of Rezdiffra and its expected use for treating MASH with moderate to advanced fibrosis, Madrigal’s aspirations to be the leading company in the MASH sector and Rezdiffra’s role as a foundational therapy, the timing and potential impact of results from the MAESTRO-NASH OUTCOMES trial, the timing for a regulatory decision by the European Commission and the planned launch of Rezdiffra in Europe. Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to: the assumptions underlying the forward-looking statements; risks of obtaining and maintaining regulatory approvals, including, but not limited to, potential regulatory delays or rejections; the challenges with the commercial launch of a new product, particularly for a company that does not have commercial experience; our history of operating losses and the possibility that we may never achieve or maintain profitability; risks associated with meeting the objectives of Madrigal’s clinical trials, including, but not limited to Madrigal’s ability to achieve enrollment objectives concerning patient numbers (including an adequate safety database), outcomes objectives and/or timing objectives for Madrigal’s trials; any delays or failures in enrollment, and the occurrence of adverse safety events; risks related to the effects of Rezdiffra’s (resmetirom’s) mechanism of action; enrollment and trial conclusion uncertainties; market demand for and acceptance of Rezdiffra; the potential inability to raise sufficient capital to fund ongoing operations as currently planned or to obtain financing on acceptable terms; our ability to service indebtedness and otherwise comply with debt covenants; outcomes or trends from competitive trials; future topline data timing or results; our ability to prevent and/or mitigate cyber-attacks; the timing and outcomes of clinical trials of Rezdiffra (resmetirom); the uncertainties inherent in clinical testing; uncertainties concerning analyses or assessments outside of a controlled clinical trial; and changes in laws and regulations applicable to our business and our ability to comply with such laws and regulations. Undue reliance should not be placed on forward looking statements, which speak only as of the date they are made. Madrigal undertakes no obligation to update any forward-looking statements to reflect new information, events, or circumstances after the date they are made, or to reflect the occurrence of unanticipated events. Please refer to Madrigal’s submissions filed with the U.S. Securities and Exchange Commission(“SEC”), for more detailed information regarding these risks and uncertainties and other factors that may cause actual results to differ materially from those expressed or implied. Madrigal specifically discusses these risks and uncertainties in greater detail in the sections appearing in Part I, Item 1A of its Annual Report on Form 10-K for the year ended December 31, 2023, filed with the SEC on February 28, 2024, and Part II, Item 1A of its Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, filed with the SEC on October 31, 2024, and as updated from time to time by Madrigal’s other filings with the SEC.

Madrigal Pharmaceuticals, Rezdiffra™ and associated logos are trademarks of Madrigal Pharmaceuticals, Inc.

Investor Contact
Tina Ventura, IR@madrigalpharma.com

Media Contact
Christopher Frates, media@madrigalpharma.com

(tables follow)
Madrigal Pharmaceuticals, Inc.
Condensed Consolidated Statement of Operations
(in thousands, except share and per share amounts)
		Three Months Ended								Twelve Months Ended
		December 31,								December 31,
			2024				2023				2024				2023
Revenues:
Product revenue, net		$	103,320			$	-			$	180,133			$	-
Operating expenses:
Cost of sales			3,445				-				6,233				-
Research and development			25,648				70,640				236,718				272,350
Selling, general and administrative			141,224				46,536				435,057				108,146
Total operating expenses			170,317				117,176				678,008				380,496
Loss from operations			(66,997	)			(117,176	)			(497,875	)			(380,496	)
Interest income			11,079				8,953				46,654				19,578
Interest expense			(3,498	)			(3,971	)			(14,671	)			(12,712	)
Net loss		$	(59,416	)		$	(112,194	)		$	(465,892	)		$	(373,630	)
Basic and diluted net loss per common share		$	(2.71	)		$	(5.68	)		$	(21.90	)		$	(19.99	)
Basic and diluted weighted average number of common shares outstanding			21,929,425				19,760,842				21,272,962				18,687,774
Condensed Consolidated Balance Sheets
(in thousands)
										December 31,
											2024				2023
Cash, cash equivalents, restricted cash and marketable securities										$	931,251			$	634,131
Trade receivables, net											53,822				-
Other current assets											47,854				3,150
Other non-current assets											9,320				3,266
Total assets										$	1,042,247			$	640,547
Liabilities and Equity
Current liabilities										$	169,277			$	118,548
Long-term liabilities											118,587				116,666
Stockholders’ equity											754,383				405,333
Total liabilities and stockholders’ equity										$	1,042,247			$	640,547

FAQ

What were Madrigal's (MDGL) Rezdiffra sales figures for Q4 and full-year 2024?

Rezdiffra achieved Q4 2024 net sales of $103.3 million and full-year 2024 net sales of $180.1 million.

What are the key findings from Rezdiffra's new two-year cirrhosis trial data?

The trial showed a mean 6.7 kPa reduction in liver stiffness, with 51% of patients achieving ≥25% reduction, representing the largest VCTE reduction reported in F4c MASH patients.

When is Madrigal (MDGL) expecting European approval for Rezdiffra?

The CHMP opinion and EU decision are expected in mid-2025, with planned launch starting in Germany in H2 2025.

How much cash does Madrigal (MDGL) have as of December 2024?

Madrigal reported $931.3 million in cash, cash equivalents, restricted cash and marketable securities as of December 31, 2024.

When will the MAESTRO-NASH OUTCOMES trial results be available for MDGL?

Results from the MAESTRO-NASH OUTCOMES trial are anticipated in 2027.