Madrigal Pharmaceuticals Completes Enrollment of Clinical Outcomes Study of Resmetirom in Patients with Compensated NASH/MASH Cirrhosis
Madrigal Pharmaceuticals (NASDAQ:MDGL) has completed enrollment for its MAESTRO-NASH OUTCOMES trial, evaluating resmetirom for treating compensated NASH cirrhosis. The study, which exceeded its initial target with 845 patients, could potentially make resmetirom the first approved medication for this high-risk population. It may also support full approval of Rezdiffra (resmetirom) in noncirrhotic NASH.
The trial is a Phase 3, double-blind, randomized, placebo-controlled study measuring progression to liver decompensation events. Patients are randomized 3:1 to receive 80 mg resmetirom or placebo daily. The study is expected to last two to three years. Madrigal's CEO, Bill Sibold, emphasized the urgent need for therapies preventing progression to decompensated cirrhosis and reducing liver transplants due to NASH.
Madrigal Pharmaceuticals (NASDAQ:MDGL) ha completato l'arruolamento per il suo trial MAESTRO-NASH OUTCOMES, che valuta il resmetirom per il trattamento di cirrosi compensata da NASH. Lo studio, che ha superato il suo obiettivo iniziale con 845 pazienti, potrebbe potenzialmente rendere il resmetirom il primo farmaco approvato per questa popolazione ad alto rischio. Potrebbe anche supportare l'approvazione completa di Rezdiffra (resmetirom) per la NASH non cirrotica.
Il trial è uno studio di fase 3, in doppio cieco, randomizzato, controllato con placebo che misura la progressione verso eventi di scompenso epatico. I pazienti sono randomizzati in un rapporto di 3:1 per ricevere 80 mg di resmetirom o placebo giornalmente. Lo studio dovrebbe durare due o tre anni. Il CEO di Madrigal, Bill Sibold, ha sottolineato l'urgenza di terapie che prevengano la progressione verso la cirrosi scompensata e riducano i trapianti di fegato dovuti alla NASH.
Madrigal Pharmaceuticals (NASDAQ:MDGL) ha completado el reclutamiento para su ensayo MAESTRO-NASH OUTCOMES, que evalúa el resmetirom para el tratamiento de cirrosis compensada por NASH. El estudio, que excedió su objetivo inicial con 845 pacientes, podría potencialmente convertir el resmetirom en el primer medicamento aprobado para esta población de alto riesgo. También podría respaldar la aprobación completa de Rezdiffra (resmetirom) en NASH no cirrótica.
El ensayo es un estudio de fase 3, doble ciego, randomizado y controlado con placebo que mide la progresión hacia eventos de descompensación hepática. Los pacientes son aleatorizados en una proporción de 3:1 para recibir 80 mg de resmetirom o placebo cada día. Se espera que el estudio dure de dos a tres años. El CEO de Madrigal, Bill Sibold, enfatizó la urgente necesidad de terapias que prevengan la progresión hacia la cirrosis descompensada y reduzcan los trasplantes de hígado debido a NASH.
마드리갈 제약(Madrigal Pharmaceuticals, NASDAQ:MDGL)은 MAESTRO-NASH OUTCOMES 임상시험의 참여자 모집을 완료했습니다. 이 시험은 보상된 NASH 간경변 치료를 위해 레즈메티롬을 평가하고 있습니다. 연구는 초기 목표인 845명의 환자를 초과 달성하였으며, 레즈메티롬이 이 고위험 집단을 위한 첫 번째 승인 약물이 될 가능성이 있습니다. 또한 비간경변 NASH에서 Rezdiffra (레즈메티롬)의 전체 승인을 지원할 수 있습니다.
이 시험은 3상, 이중 맹검, 무작위 배정, 위약 대조 연구로, 간의 탈보상 사건으로의 진행을 측정합니다. 환자들은 매일 80 mg의 레즈메티롬 또는 플라시보를 받기 위해 3:1의 비율로 무작위로 배정됩니다. 이 연구는 2~3년 동안 진행될 것으로 예상됩니다. 마드리갈의 CEO인 빌 시볼드(Bill Sibold)는 탈보상 간경변으로의 진행을 예방하고 NASH로 인한 간 이식을 줄이기 위한 치료법의 긴급한 필요성을 강조했습니다.
Madrigal Pharmaceuticals (NASDAQ:MDGL) a achevé le recrutement pour son essai MAESTRO-NASH OUTCOMES, qui évalue le resmetirom pour le traitement de cirrhose compensée par NASH. L'étude, qui a dépassé son objectif initial avec 845 patients, pourrait potentiellement faire du resmetirom le premier médicament approuvé pour cette population à haut risque. Elle pourrait également soutenir l'approbation complète de Rezdiffra (resmetirom) dans la NASH non cirrhotique.
L'essai est un étude de phase 3, en double aveugle, randomisée, contrôlée contre placebo qui mesure la progression vers des événements de décompensation hépatique. Les patients sont randomisés dans un rapport de 3:1 pour recevoir 80 mg de resmetirom ou un placebo chaque jour. L'étude devrait durer deux à trois ans. Le PDG de Madrigal, Bill Sibold, a souligné le besoin urgent de thérapies empêchant la progression vers la cirrhose décompensée et réduisant les transplantations hépatiques dues à la NASH.
Madrigal Pharmaceuticals (NASDAQ:MDGL) hat die Rekrutierung abgeschlossen für seine MAESTRO-NASH OUTCOMES-Studie, die Resmetirom zur Behandlung von kompensierter NASH-Zirrhose evaluiert. Die Studie übertraf ihr ursprünglich gesetztes Ziel mit 845 Patienten und könnte Resmetirom potenziell zum ersten zugelassenen Medikament für diese Hochrisikopopulation machen. Es könnte auch die Vollgenehmigung von Rezdiffra (Resmetirom) bei nicht-zirrhotischer NASH unterstützen.
Die Studie ist eine Phase 3, doppelblinde, randomisierte, placebo-kontrollierte Untersuchung, die die Fortschreitung zu Leberdekompensationsereignissen misst. Die Patienten werden im Verhältnis 3:1 randomisiert, um täglich 80 mg Resmetirom oder ein Placebo zu erhalten. Die Studie wird voraussichtlich zwei bis drei Jahre dauern. Madrigals CEO, Bill Sibold, betonte den dringenden Bedarf an Therapien, die eine Fortschreitung zu dekompensierter Zirrhose verhindern und Lebertransplantationen aufgrund von NASH reduzieren.
- Completed enrollment for MAESTRO-NASH OUTCOMES trial with 845 patients, exceeding initial target
- Potential to be the first approved medication for compensated NASH cirrhosis
- May support full approval of Rezdiffra (resmetirom) in noncirrhotic NASH
- Positive 52-week data from 180 patients with compensated NASH cirrhosis in Phase 3 MAESTRO-NAFLD-1 study
- Study duration of two to three years before results are available
- No guaranteed positive outcome or approval of the drug
Insights
The completion of enrollment for the MAESTRO-NASH OUTCOMES study is a significant milestone for Madrigal Pharmaceuticals. This Phase 3 trial evaluates resmetirom in patients with compensated NASH cirrhosis, a condition with no currently approved treatments. The study's potential impact is substantial:
- If successful, resmetirom could become the first approved medication for compensated NASH cirrhosis, addressing a critical unmet need.
- The trial may support full approval of Rezdiffra (resmetirom) for noncirrhotic NASH, expanding its potential market.
- With
845 patients enrolled, exceeding the initial target, the study has robust statistical power. - The primary endpoint focuses on liver-related outcome events, directly measuring clinical benefit.
The study's design, including its 3:1 randomization and focus on well-compensated NASH cirrhosis patients with metabolic risk factors, enhances its relevance to the target population. The expected 2-3 year duration for event accrual suggests results may be available in the near-to-medium term, potentially catalyzing significant market movement upon readout.
This clinical trial milestone has substantial implications for Madrigal's financial outlook and market position:
- Successful completion could significantly expand Madrigal's addressable market, potentially including both cirrhotic and noncirrhotic NASH patients.
- With NASH being a leading cause of liver transplantation, a successful treatment could capture a large, growing market.
- The company's
4.66 billion market cap suggests high investor expectations, which this trial could validate or challenge. - Positive results could lead to:
- Increased partnership opportunities
- Potential for premium pricing given the lack of approved alternatives
- Enhanced competitive positioning in the NASH space
However, investors should note that the
- Positive results from the MAESTRO-NASH OUTCOMES study could make resmetirom the first medication approved for patients with compensated NASH cirrhosis, a population at high risk of progressing to adverse liver-related outcomes
- Study may also support full approval of RezdiffraTM (resmetirom) in noncirrhotic NASH
CONSHOHOCKEN, Pa., Oct. 21, 2024 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a biopharmaceutical company focused on delivering novel therapeutics for nonalcoholic steatohepatitis (NASH)/metabolic dysfunction-associated steatohepatitis (MASH), today announced the MAESTRO-NASH OUTCOMES trial evaluating resmetirom for the treatment of patients with compensated NASH cirrhosis has completed enrollment.
Bill Sibold, Chief Executive Officer of Madrigal, stated, “The MAESTRO-NASH OUTCOMES trial is important for patients and the NASH field more broadly because there is an urgent unmet need for therapies that can prevent progression to the devastating complications of decompensated cirrhosis and by extension reduce the need for liver transplants due to NASH. NASH is already the leading cause of liver transplantation among women in the U.S. and second-leading cause among men. Today’s enrollment milestone brings us one step closer to our goal of delivering the first effective therapy to patients who currently have no approved treatment options for compensated NASH cirrhosis. A positive outcome for this study is also expected to support the full approval of Rezdiffra for noncirrhotic NASH.”
Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal, added, “Our confidence in the MAESTRO-NASH OUTCOMES study is grounded in the antifibrotic profile of resmetirom as a liver-directed THR-β agonist and supported by positive 52-week data from 180 patients with compensated NASH cirrhosis studied in the Phase 3 MAESTRO-NAFLD-1 study. Madrigal is committed to long-term leadership in NASH R&D, and we believe our fully enrolled outcomes studies will play a central role in shaping the NASH treatment paradigm over the next decade.”
MAESTRO-NASH OUTCOMES is a Phase 3, double-blind, randomized, placebo-controlled study that noninvasively measures progression to liver decompensation events in 845 patients with compensated NASH cirrhosis, exceeding the initial enrollment target. The primary endpoint of MAESTRO-NASH OUTCOMES is the incidence of composite liver-related outcome events. Key inclusion criteria are well-compensated NASH cirrhosis (Child-Pugh A) and presence of three metabolic risk factors (metabolic syndrome). Patients are randomized 3:1 in a blinded manner to receive 80 mg resmetirom or matching placebo, given orally once daily. The study duration is expected to be two to three years for accrual of the required number of composite clinical outcome events.
About NASH
Nonalcoholic steatohepatitis (NASH) is a more advanced form of nonalcoholic fatty liver disease (NAFLD). NASH is a leading cause of liver-related mortality and an increasing burden on healthcare systems globally. Additionally, patients with NASH, especially those with more advanced metabolic risk factors (hypertension, concomitant type 2 diabetes), are at increased risk for adverse cardiovascular events and increased morbidity and mortality.
Once patients progress to NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis), the risk of adverse liver outcomes increases dramatically. When a patient with NASH progresses to cirrhosis, their risk of liver-related mortality increases by more than 42 percent. NASH is rapidly becoming the leading cause of liver transplantation in the U.S.
Madrigal estimates that approximately 1.5 million patients have been diagnosed with NASH in the U.S., of which approximately 525,000 have NASH with moderate to advanced liver fibrosis. Madrigal is focusing on approximately 315,000 diagnosed patients with NASH with moderate to advanced liver fibrosis under the care of the liver specialist physicians during the launch of Rezdiffra.
NASH is also known as metabolic dysfunction associated steatohepatitis (MASH). In 2023, global liver disease medical societies and patient groups came together to rename the disease, with the goal of establishing an affirmative, non-stigmatizing name and diagnosis. Nonalcoholic fatty liver disease (NAFLD) was renamed metabolic dysfunction-associated steatotic liver disease (MASLD); NASH was renamed MASH; and an overarching term, steatotic liver disease (SLD), was established to capture multiple types of liver diseases associated with fat buildup in the liver. In addition to liver disease, patients with MASH have at least one related comorbid condition (e.g., obesity, hypertension, dyslipidemia, or type 2 diabetes).
About the Resmetirom Phase 3 Program
Resmetirom is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of NASH. Madrigal is currently conducting multiple Phase 3 clinical trials to evaluate the safety and efficacy of resmetirom for the treatment of NASH:
- The pivotal MAESTRO-NASH (Moderate to Advanced Fibrosis) study included a 52-week biopsy assessment that supported accelerated approval and an ongoing 54-month outcomes study designed to generate confirmatory data that, if positive, will help verify the clinical benefit of Rezdiffra and support full approval. The primary results of the MAESTRO-NASH trial were published in the New England Journal of Medicine in February 2024.
- MAESTRO-NASH OUTCOMES (Compensated Cirrhosis) evaluates progression to liver decompensation events in patients with compensated NASH cirrhosis treated with resmetirom versus placebo. A positive outcome is expected to support the full approval of Rezdiffra for noncirrhotic NASH and expand the eligible patient population for Rezdiffra with an additional indication in patients with compensated NASH cirrhosis.
- The MAESTRO-NAFLD-1 (Safety) study was designed to noninvasively evaluate the safety and tolerability of resmetirom and provide a larger safety database to support regulatory benefit-risk assessment. The primary results from the MAESTRO-NAFLD-1 trial were published in Nature Medicine in October 2023. MAESTRO-NAFLD-OLE, an open-label active treatment extension of MAESTRO-NAFLD-1, is ongoing to collect additional safety data in patients with noncirrhotic NASH and patients with compensated NASH cirrhosis.
Data from the 52-week portion of MAESTRO-NASH, together with data from MAESTRO-NAFLD-1, MAESTRO-NAFLD-OLE, Phase 2 and Phase 1 data, including safety parameters, formed the basis for accelerated approval of Rezdiffra for treatment of NASH with moderate to advanced liver fibrosis.
About Madrigal Pharmaceuticals
Madrigal Pharmaceuticals, Inc. (Nasdaq: MDGL) is a biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), 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 NASH. 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, that are based on Madrigal’s beliefs and assumptions and on information currently available to it but are subject to factors beyond its control. Forward-looking statements reflect management’s current knowledge, assumptions, judgment and expectations regarding future performance or events. Forward-looking statements include all statements that are not historical facts; statements referenced by forward-looking statement identifiers; and statements regarding: Rezdiffra and its expected use for treating NASH with moderate to advanced fibrosis.
Forward-looking statements can be identified by terms such as “accelerate,” “achieve,” “allow,” “anticipates,” “appear,” “be,” “believes,” “can,” “confidence,” “continue,” “could,” “demonstrates,” ”design,” “estimates,” “expectation,” “expects,” “forecasts,” “future,” “goal,” “help,” “hopeful,” “inform,” “informed,” “intended,” “intends,” “may,” “might,” “on track,” “planned,” “planning,” “plans,” “positions,” “potential,” “powers,” “predicts,” ”predictive,” “projects,” “seeks,” “should,” “will,” “will achieve,” “will be,” “would” or similar expressions and the negatives of those terms.
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; risks associated with meeting the objectives of Madrigal’s clinical studies, 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 studies; any delays or failures in enrollment, and the occurrence of adverse safety events; risks related to the mechanism of action of Rezdiffra; enrollment and trial conclusion uncertainties; market demand for and acceptance of our product; the potential inability to raise sufficient capital to fund ongoing operations as currently planned or to obtain financings on terms similar to those arranged in the past; the ability to service indebtedness and otherwise comply with debt covenants; outcomes or trends from competitive studies; future topline data timing or results; our ability to prevent and/or mitigate cyber-attacks; the timing and outcomes of clinical studies of Rezdiffra; the uncertainties inherent in clinical testing; and uncertainties concerning analyses or assessments outside of a controlled clinical trial. 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, or 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 June 30, 2024, filed with the SEC on August 7, 2024, and as updated from time to time by Madrigal’s other filings with the SEC.
Investor Contact
Tina Ventura, IR@madrigalpharma.com
Media Contact
Christopher Frates, media@madrigalpharma.com
FAQ
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