Thyroid Hormone Receptor-beta (THR-B) Agonist - Target Population, Competitive Landscape, and Market Forecast - 2034

Key Highlights:

• THR-B agonists are a targeted therapeutic class that selectively modulate thyroid hormone signaling in the liver, offering disease-modifying potential by addressing underlying metabolic and fibrotic pathways.
• The current THR-B agonist landscape is led by a single approved therapy for Metabolic Dysfunction-associated Steatohepatitis (MASH), with Madrigal Pharmaceuticals at the forefront. However, the market is becoming increasingly competitive, as several companies-including Viking Therapeutics, Aligos Therapeutics, and others-are advancing their candidates through various stages of clinical development, reflecting continued innovation and growing momentum in the field.
• Key emerging THR-B agonists such as VK2809, ALG-055009, and VK0214 are demonstrating therapeutic potential across a range of indications, with efforts focused on expanding treatment options in both metabolic and rare genetic diseases.
• In November 2024, Viking Therapeutics presented 52-week secondary endpoint results from the Phase IIb VOYAGE trial of VK2809 in biopsy-confirmed NASH/MASH at the 75th Liver Meeting hosted by the American Association for the Study of Liver Diseases (AASLD), further supporting its potential in advancing MASH therapy.

DelveInsight's "THR-B Agonist" - Target Population, Competitive Landscape, and Market Forecast - 2034" report delivers an in-depth understanding of the THR-B agonist, historical and projected epidemiological data, competitive landscape as well as the THR-B agonist market trends in the United States, EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan.

The THR-B agonist market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted 7MM THR-B agonist market size from 2020 to 2034. The report also covers current THR-B agonist treatment practices/algorithms and unmet medical needs to curate the best opportunities and assess the market's potential.

Geography Covered:

• The United States
• EU4 (Germany, France, Italy, and Spain) and the United Kingdom
• Japan

THR-B Agonist Understanding and Treatment Algorithm

THR-B Agonist Overview

THR-B, the beta isoform of the thyroid hormone receptor, plays a central role in regulating lipid metabolism, cholesterol transport, bile acid synthesis, and mitochondrial function, particularly in liver tissue. Its selective activation promotes hepatic fat oxidation, reduces inflammation, and downregulates fibrogenic pathways-mechanisms directly relevant to the treatment of MASH. Additionally, THR-B activation induces expression of the ABCD2 gene, which encodes a compensatory peroxisomal transporter, offering therapeutic potential in rare genetic disorders such as X-ALD by reducing very long-chain fatty acid accumulation.

The therapeutic relevance of THR-B lies in its ability to deliver metabolic benefits while avoiding adverse effects associated with THR-a activation, such as cardiac and skeletal toxicity. Selective THR-B agonists are being designed to maximize liver targeting and subtype specificity, aiming to improve liver histology, reverse steatosis, and prevent progression to cirrhosis. Clinical development is focused on confirming these benefits through long-term safety and efficacy data, with ongoing trials in both MASH and X-ALD further supporting THR-B as a key molecular target across metabolic and rare disease landscapes.

THR-B Agonist Clinical Relevance

One THR-B agonist therapy has received regulatory approval for MASH, highlighting the clinical significance of targeting thyroid hormone receptor beta in metabolic liver disease. THR-B regulates key pathways involved in lipid metabolism, hepatic fat oxidation, and fibrogenesis, making it a central driver in the pathophysiology of MASH. This milestone has validated THR-B as a therapeutic target and spurred further development of selective agonists aimed at reversing steatosis, reducing fibrosis, and preventing disease progression. Beyond MASH, THR-B agonists are also being investigated in rare metabolic disorders such as X-linked adrenoleukodystrophy, reinforcing their broader potential across liver- and peroxisome-related diseases.

The emerging pipeline of THR-B agonists is being investigated across a range of metabolic and genetic conditions, including noncirrhotic and cirrhotic MASH, as well as X-ALD. These agents are designed to selectively activate hepatic THR-B, promoting lipid clearance, reducing hepatic steatosis, and attenuating fibrogenic and inflammatory signaling. Some candidates are also being evaluated for their ability to modulate peroxisomal function and lower toxic lipid accumulation in rare genetic disorders. This targeted approach underscores the broad therapeutic potential of THR-B agonists in both early and advanced stages of liver disease, as well as select rare metabolic conditions.

THR-B Agonist Epidemiology

The THR-B agonist epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented as total cases in selected indications for THR-B Agonist, total eligible patient pool in selected indications for THR-B Agonist, and total treated cases in selected indications for THR-B Agonist in the 7MM covering the United States, EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan from 2020 to 2034.

MASH

• In 2024, the total diagnosed prevalent cases of MASH in the US were estimated at approximately 5 million cases.
• Among the EU4 and the UK, Germany reported the highest number of diagnosed prevalent MASH cases in 2024, with approximately 800 thousand cases, highlighting a substantial disease burden in the region.
• In Japan in 2024, the estimated distribution of MASH cases by fibrosis stage was approximately 180 thousand at F0, 245 thousand at F1, 140 thousand at F2, 85 thousand at F3, and 35 thousand at F4.

X-ALD

• X-ALD is the most common peroxisomal disorder, with an estimated birth incidence of 1 in 17,000 newborns (male and female combined).
• The condition is caused by mutations in the ABCD1 gene, which is located on the X chromosome. Because females have two X chromosomes, those who carry a mutation in one copy typically also have a functioning copy, making them less likely to develop symptoms. As a result, X-ALD primarily affects males.
• X-ALD presents in multiple clinical forms with varying severity. One of the most severe and prevalent subtypes is childhood cerebral ALD (CCALD), which occurs in approximately 30% of affected individuals.

THR-B Agonist Drug Chapters

The drug chapter segment of the THR-B agonist reports includes a detailed analysis of THR-B agonist early-, mid-, and late-stage (Phase I, Phase II and Phase III) pipeline drugs. It also helps understand the THR-B agonist's clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug the latest news and press releases.

Marketed Drugs

Only one THR-B agonist, REZDIFFRA (resmetirom, MGL-3196), has been approved to date for the treatment of adults with noncirrhotic MASH and moderate to advanced liver fibrosis (F2-F3), as an adjunct to diet and exercise.

REZDIFFRA (resmetirom, MGL-3196): Madrigal Pharmaceuticals

REZDIFFRA (resmetirom) is a THR-B agonist granted accelerated approval by the US FDA in March 2024 as an adjunct to diet and exercise for adults with noncirrhotic MASH and moderate to advanced fibrosis (F2-F3). Approval was based on improvements in MASH and fibrosis; continued approval is subject to confirmation of clinical benefit in ongoing trials.

REZDIFFRA is also being developed for the treatment of compensated MASH cirrhosis (stage F4c) and is currently being evaluated in the fully enrolled Phase III MAESTRO-NASH OUTCOMES trial, which is assessing its impact on progression to liver decompensation events.

In June 2025, Madrigal received a positive Committee for Medicinal Products for Human Use (CHMP) opinion for REZDIFFRA (resmetirom) for the treatment of MASH with moderate to advanced fibrosis, based on data from the Phase III MAESTRO-NASH trial. A final decision from the European Commission is expected by August 2025 and, if approved, REZDIFFRA would become the first authorized therapy for MASH in the EU.

Following EMA approval, Madrigal plans to roll out REZDIFFRA across Europe on a country-by-country basis, beginning with Germany in the second half of 2025, marking the first availability of an approved treatment for MASH-related liver fibrosis in the region.

In May 2025, Madrigal announced Phase III data showing REZDIFFRA significantly reduced liver stiffness and portal hypertension risk in patients with compensated MASH cirrhosis, with 65% moving to lower risk categories by year two.

Emerging Drugs

VK2809: Viking Therapeutics

VK2809 is an orally available, liver-targeted, and subtype-selective THR-beta agonist, designed to modulate lipid metabolism with high specificity. By selectively activating THR-B in liver tissue, it upregulates genes involved in lipid metabolism and clearance, leading to improvements in cholesterol and lipoprotein levels. VK2809 has shown significant therapeutic potential in lipid disorders, meeting both primary and secondary endpoints in the Phase IIb VOYAGE study in patients with biopsy-confirmed NASH/MASH and fibrosis, as well as in a Phase IIa study in patients with elevated LDL-C and NAFLD.

In June 2024, Viking Therapeutics announced positive 52-week histologic results from the Phase IIb VOYAGE study in patients with biopsy-confirmed NASH, further supporting VK2809's potential in treating MASH with fibrosis.

ALG-055009: Aligos Therapeutics

ALG-055009 is an investigational oral small molecule THR-beta agonist developed by Aligos Therapeutics for the treatment of MASH. Engineered for best-in-class potency and selectivity, it is designed to enhance lipid metabolism, promote fat oxidation, and improve bile acid synthesis, with the potential to reverse hepatic steatosis. By selectively targeting THR-B, ALG-055009 aims to reduce systemic lipid levels while minimizing off-target effects linked to THR-a activation. Aligos Therapeutics is actively exploring options to support continued development, including potential out-licensing opportunities.

In November 2024, Aligos Therapeutics presented positive data from the Phase IIa HERALD study of ALG-055009 in MASH subjects through a late-breaker oral presentation at The Liver Meeting 2024, hosted by AASLD.

In September 2024, topline Phase IIa HERALD data showed ALG-055009 met its primary endpoint, achieving significant liver fat reduction at Week 12 as measured by MRI-PDFF; Phase IIb preparations are underway, with completion expected by mid-2025 and trial designs under evaluation.

VK0214: Viking Therapeutics

VK0214 is a novel, orally available small molecule THR-B agonist being developed by Viking Therapeutics for the treatment of X-ALD, with a focus on the adrenomyeloneuropathy form. It has been granted orphan drug designation by the US FDA. In a placebo-controlled Phase Ib trial in adult males with AMN, VK0214 was shown to be safe and well-tolerated with once-daily dosing over 28 days, and led to significant reductions in plasma levels of very long-chain fatty acids (VLCFAs) and other lipids. By upregulating expression of ABCD2, which encodes a compensatory transporter (ALDRP), VK0214 aims to normalize VLCFA metabolism and potentially mitigate demyelination. This mechanism offers promise for addressing all forms of X-ALD, a progressive metabolic disorder with no approved therapies.

In October 2024, Viking reported positive results from its Phase Ib clinical trial of VK0214, which met both primary and secondary endpoints. VK0214 was shown to be safe and well-tolerated with once-daily dosing over 28 days. Most treatment-emergent adverse events were mild to moderate, with a single severe event-a wrist fracture-occurring in a placebo-treated participant.

In June 2021, Viking reported positive results from its first-in-human Phase I trial of VK0214, which included both single and multiple ascending dose cohorts in healthy volunteers. The study met its primary and secondary objectives, with VK0214 shown to be safe and well-tolerated at all dose levels, and no serious adverse events or dose-related safety signals observed.

THR-B Agonist Market Outlook

The THR-B agonist market is gaining strong momentum, driven by the rising global burden of metabolic diseases such as MASH and rare genetic disorders like X-ALD. Advancements in thyroid hormone receptor research have reinforced the therapeutic value of selectively targeting THR-B, particularly in liver tissue, supporting its development across these high-need areas.

A robust mid- to late-stage pipeline-including candidates such as VK2809 and VK0214 from Viking Therapeutics and ALG-055009 from Aligos Therapeutics-reflects ongoing innovation and growing competition, signaling strong momentum for future growth in both the MASH and X-ALD treatment landscapes.

THR-B Agonist Uptake

This section focuses on the uptake rate of potential approved and emerging THR-B agonist expected to be launched in the market during 2020-2034.

THR-B Agonist Pipeline Development Activities

The report provides insights into different therapeutic candidates in Phase III, Phase II and Phase I. It also analyzes key players involved in developing targeted therapeutics.

The presence of numerous drugs under different stages is expected to generate immense opportunity for THR-B agonist market growth over the forecasted period.

Pipeline Development Activities

The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for THR-B agonist emerging therapies.

KOL Views

To keep up with current and future market trends, we take Industry Experts' opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry experts were contacted for insights on THR-B agonist's evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, drug uptake, along challenges related to accessibility.

DelveInsight's analysts connected with 25+ KOLs to gather insights; however, interviews were conducted with 10+ KOLs in the 7MM.

Their opinion helps understand and validate current and emerging therapy treatment patterns or THR-B agonists market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

Qualitative Analysis

We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of disease diagnosis, patient awareness, patient burden, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided. These pointers are based on the analyst's discretion and assessment of the patient burden, cost analysis, and existing and evolving treatment landscape.

Market Access and Reimbursement

The report further provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenario of approved therapies, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc.

Scope of the Report:

• The report covers a segment of key events, an executive summary, and a descriptive overview of THR-B agonist, explaining its mechanism, and therapies (current and emerging).
• Comprehensive insight into the Competitive Landscape, and forecasts, the future growth potential of treatment rate, drug uptake, and drug information have been provided.
• Additionally, an all-inclusive account of the current and emerging therapies and the elaborative profiles of late-stage and prominent therapies will impact the current landscape.
• A detailed review of the THR-B agonist market, historical and forecasted market size, market share by therapies, detailed assumptions, and rationale behind our approach is included in the report, covering the 7MM drug outreach.
• The report provides an edge while developing business strategies, by understanding trends, through SWOT analysis expert insights/KOL views, and treatment preferences that help shape and drive the 7MM THR-B agonist market.

THR-B Agonist Report Insights

• THR-B Agonist Targeted Patient Pool
• THR-B Agonist Therapeutic Approaches
• THR-B Agonist Pipeline Analysis
• THR-B Agonist Market Size and Trends
• Existing and Future Market Opportunity

THR-B Agonist Report Key Strengths

• 10 Years Forecast
• The 7MM Coverage
• Key Cross Competition
• Drugs Uptake and Key Market Forecast Assumptions

THR-B Agonist Report Assessment

• Current Treatment Practices
• Unmet Needs
• Pipeline Product Profiles
• Market Attractiveness
• Qualitative Analysis (SWOT)

Key Questions:

• What was the THR-B agonist total market size, the market size by therapies, market share (%) distribution in 2020, and what would it look like in 2034? What are the contributing factors for this growth?
• Which drug is going to be the largest contributor in 2034?
• Which is the most lucrative market for THR-B agonist?
• Which drug accounts for maximum sales among THR-B agonists?
• What are the pricing variations among different geographies for approved therapies?
• How has the reimbursement landscape for THR-B agonists evolved since the first one was approved? Do patients face any access issues driven by reimbursement decisions?
• What are the risks, burdens, and unmet needs of treatment with THR-B agonist? What will be the growth opportunities across the 7MM for the patient population on THR-B agonist?
• What are the key factors hampering the growth of the THR-B agonist market?
• What are the indications for which recent novel therapies and technologies have been developed to overcome the limitations of existing treatments?
• What key designations have been granted to the therapies for THR-B agonist?
• What is the cost burden of approved therapies on the patient?
• Patient acceptability in terms of preferred therapy options as per real-world scenarios?
• What are the country-specific accessibility issues of expensive, recently approved therapies?

Reasons to buy:

• The report will help develop business strategies by understanding the latest trends and changing dynamics driving the THR-B agonist market.
• Understand the existing market opportunities in varying geographies and the growth potential over the coming years.
• Distribution of historical and current patient share based on real-world prescription data along with reported sales of approved products in the US, EU4 (Germany, France, Italy, and Spain) the UK, and Japan.
• Identifying strong upcoming players in the market will help devise strategies to help get ahead of competitors.
• Detailed analysis and ranking of indication-wise current and emerging therapies under the attribute analysis section to provide visibility around leading indications.
• Highlights of Access and Reimbursement policies of approved therapies, barriers to accessibility of expensive off-label therapies, and patient assistance programs.
• To understand Key Opinion Leaders' perspectives around the accessibility, acceptability, and compliance-related challenges of existing treatment to overcome barriers in the future.
• Detailed insights on the unmet needs of the existing market so that the upcoming players can strengthen their development and launch strategy.