Thr-β Agonist Market By Fibrosis Stage (F2, F3); By Diagnosis Pathway (Biopsy-Confirmed, NIT-Confirmed); By Treatment Setting (Monotherapy, Combination Therapy); By Geography, Segment Revenue Estimation, Forecast, 2025–2035

INTRODUCTION AND STRATEGIC CONTEXT

The Global Thr-β Agonist Market is set to expand rapidly between 2025 and 2035, growing from under $1 billion in 2025 to nearly $11 billion by 2030, according to Strategic Market Research. This projected trajectory — driven by a compelling mix of clinical unmet need, first-in-class approvals, and diagnostic expansion — signals the emergence of a newly defined pharmacologic category. Over the forecast period, the market will register an impressive CAGR as it matures from a single-asset launch environment into a competitive multi-asset class.

 

Thr-β (Thyroid hormone receptor beta) agonists are a novel therapeutic class designed to target non-cirrhotic MASH (Metabolic dysfunction-Associated Steatohepatitis), specifically in patients with fibrosis stages F2 and F3. Until 2024, no pharmacologic treatment existed for this population. The approval and U.S. launch of Rezdiffra (resmetirom) marked a fundamental shift — effectively creating monetizable demand in a previously untapped segment. The therapy has quickly validated real-world demand, achieving quarterly net sales of $212.8 million and initiating treatment for approximately 23,000 patients by mid-2025.

 

Unlike traditional markets built on patient volume alone, the Thr-β agonist space is strategically shaped by diagnostic infrastructure, payer eligibility criteria, and specialist adoption curves. Even in high-prevalence regions like the U.S., Europe, and Japan, only a subset of diagnosed F2–F3 MASH patients (~4 million globally) are addressable in the near term. This constraint underscores a critical insight: the market is not prevalence-driven — it’s system-limited. Countries with established non-invasive testing (NIT) protocols and payer coverage frameworks will unlock commercial value faster.

 

From a stakeholder perspective, the ecosystem is widening fast. Madrigal Pharmaceuticals, the maker of Rezdiffra, currently enjoys first-mover status. But several competitors — including Viking Therapeutics (VK2809) and Terns Pharmaceuticals (TERN-501) — are moving through Phase II/III development, aiming for post-2027 entry. Meanwhile, payers are recalibrating access models around non-biopsy diagnostics, and health systems are reorienting liver disease screening programs to capture earlier-stage MASH.

 

Strategically, this market is less about switching and more about expansion. Follow-on Thr-β agonists are expected to complement — not cannibalize — Rezdiffra’s patient base. And as combination therapy emerges (especially with GLP-1s or metabolic agents), the market’s size ceiling could expand well beyond current projections.

 

To be honest, this isn’t just a product category. It’s a commercial reset for metabolic liver disease. A market previously defined by inertia and unmet need is now being reshaped by clinical validation, diagnostic enablement, and payer responsiveness — all converging into a durable, multi-billion-dollar therapeutic segment by 2030.

 

MARKET SEGMENTATION AND FORECAST SCOPE

The global Thr-β agonist market is structured along multiple segmentation axes, each grounded in how eligibility, diagnosis, and treatment persistence define commercial opportunity. Unlike traditional chronic disease markets, this category is not segmented by demographics or symptom severity — it’s stratified by fibrosis stage, diagnosis method, treatment modality, and geography. Below is a breakdown of the core segmentation logic embedded within the forecast model.

By Fibrosis Stage

The single most decisive segmentation factor is fibrosis stage, which determines both eligibility and urgency. Commercially, the market is anchored in the F2 and F3 segments — collectively accounting for ~4 million diagnosed patients globally as of 2025.

• F2 MASH: These patients represent moderate fibrosis with progression risk. They account for approximately 20–25% of the overall MASH pool.

• F3 MASH: Considered pre-cirrhotic, this segment has the highest clinical urgency and therapeutic value. These patients represent 15–20% of MASH cases and are typically prioritized in early treatment adoption.

Fibrosis staging is not just clinical — it’s commercial. Patients with F0–F1 are rarely reimbursed, while those with F4 (cirrhosis) are currently excluded under most payer frameworks.

 

By Diagnosis Pathway

A second critical layer of segmentation stems from diagnostic modality:

• Biopsy-confirmed patients: Historically the only path to eligibility, but now declining in favor of less invasive options.

• Non-invasive test (NIT)–confirmed patients: This includes FibroScan, MRI-PDFF, and blood-based panels. NIT adoption is the largest unlock lever for future market expansion — particularly in countries with payer-approved protocols.

In 2024, biopsy-based diagnosis still dominates, but NIT-driven expansion is expected to overtake by 2028, especially in the U.S. and Japan.

 

By Treatment Modality

Therapy modality splits the market between:

• Rezdiffra monotherapy: The current standard, dominating revenue in early forecast years.

• Rezdiffra-based combination therapy: Expected to emerge after 2028, especially in patients with comorbid dyslipidemia or obesity. Combinations with GLP-1s or PPAR agonists are being explored for broader metabolic benefits.

Early adoption is monotherapy-heavy. But once outcomes data solidify and payers approve co-initiations, combination regimens will shift the pricing and volume dynamics.

 

By Region

The geographic forecast model segments into:

• North America: Currently accounts for the majority of commercial value, led by the U.S. with high diagnosis rates and rapid payer uptake.

• Europe (EU5 + UK): Roughly ~3 million MASH patients diagnosed as of 2023, with payer-driven access shaping the pace of expansion.

• Asia Pacific: Japan is highly penetrable due to diagnosis rigor; China has massive prevalence but limited commercial contribution through 2030.

• Rest of World: Includes Latin America, Middle East, and Africa — regions where diagnostic gaps and affordability barriers limit uptake.

 

Scope of Forecast Model

• Base year: 2024

• Forecast window: 2025–2035

• Revenue modeled: Net revenue (post-discount), therapy-specific

• Treated patient counts: Modeled annually by region and fibrosis stage

• Scenarios included: Single-asset, two-asset, and multi-asset market entry

• Sensitivity variables: Pricing elasticity, diagnostic adoption, treatment persistence

To be clear, this market is not segmented like most chronic disease landscapes. It’s filtered through fibrosis-stage eligibility, diagnosis infrastructure, and access gatekeeping. That creates both precision and constraint — but also allows for highly targeted forecast modeling.

 

MARKET TRENDS AND INNOVATION LANDSCAPE

What makes the Thr-β agonist market unique isn’t just its speed of growth — it’s how innovation is changing who qualifies, how they’re diagnosed, and how long they stay on therapy. From evolving diagnostic algorithms to multi-mechanism combination therapies, the space is moving fast — not in scale alone, but in sophistication.

Non-Invasive Diagnostics Are the Linchpin of Market Expansion

One of the most significant shifts underway is the move away from liver biopsies toward non-invasive tests (NITs). FibroScan, MRI-PDFF, and blood-based fibrosis panels like FIB-4 and ELF are quickly becoming the preferred diagnostic route. This isn’t just a clinical upgrade — it’s a commercial multiplier.

Markets with high NIT penetration — like the U.S., Japan, and parts of Western Europe — are already seeing faster treated patient uptake. As NITs become payer-recognized standards, the eligible pool of F2–F3 MASH patients expands significantly, often by double-digit percentages.

As one hepatology specialist said, “NITs unlock treatment not just by avoiding biopsies — but by making screening scalable in primary care.”

 

Category-Creation Effect: Rezdiffra as the Clinical Benchmark

The approval of Rezdiffra (resmetirom) didn’t just start the market — it set the standard. With strong histology and imaging data from the MAESTRO-NASH trial, Rezdiffra demonstrated improvements in both fibrosis and MASH resolution, making it the clinical anchor against which all future entrants will be benchmarked.

The market isn’t following a traditional “best-in-class” arc — it’s following a category-creation arc, where the first approved agent shapes everything from pricing expectations to payer logic to diagnostic algorithms.

That said, outcomes data (expected by ~2027) will be a key inflection point. If Rezdiffra demonstrates cardiovascular or mortality benefit, the treatment window could expand to include F4 patients, a segment currently excluded from most labels and models.

 

Pipeline Competition: Expansionary, Not Cannibalistic

Several Thr-β agonists are moving through the pipeline, with VK2809 (Viking Therapeutics) and TERN-501 (Terns Pharmaceuticals) leading the charge. VK2809, in particular, has reported promising MRI-PDFF liver fat reduction rates (37–55%), and is expected to enter Phase 3 trials imminently.

But make no mistake — these agents are not entering a saturated market. They’re entering a structurally constrained one, and their primary role will be to expand the treated population, not displace Rezdiffra.

Switching will remain low unless dramatic safety or outcomes differentiation emerges — something not yet supported by available Phase II data.

 

Combination Therapy Is the Next Horizon

Beyond monotherapy, the future of this market lies in combination strategies — particularly with GLP-1s, PPARs, or FGF21 analogs. These agents address complementary metabolic and inflammatory pathways, making dual-target regimens a logical next step.

Pharmaceutical developers are already exploring sequencing and simultaneous initiation options. However, payer acceptance and outcomes data will determine how quickly these regimens enter clinical practice.

Expect this to shift the market from "fixed-dose therapy" to "modular care models" — personalized regimens based on patient comorbidity and fibrosis trajectory.

 

Innovation in Trial Design and Label Strategy

Finally, developers are shifting trial strategies away from invasive endpoints. Imaging-based markers (like MRI-PDFF or cT1) and serum biomarkers are increasingly used as surrogate endpoints — accelerating trial timelines and regulatory pathways.

Label strategies are also adapting. Instead of chasing broader populations, developers are focusing on precision eligibility (F2–F3, biopsy-free) and long-term maintenance therapy as the commercial sweet spot.

This shift supports pricing durability, improves adherence, and strengthens payer contracts — especially in the U.S. and Japan, where treatment duration often determines ROI models.

 

To sum up: this isn’t a market where innovation is “nice to have.” It’s the foundation. Diagnostics, trial endpoints, payer logic, and combination strategies are all converging to redefine what qualifies as a treatable MASH patient. And whoever controls those levers — controls the next $10B in revenue.

 

COMPETITIVE INTELLIGENCE AND BENCHMARKING

The Thr-β agonist market isn’t your typical free-for-all. It’s a high-barrier, narrow-eligibility field where being first approved matters more than being first discovered. While Madrigal Pharmaceuticals currently commands the field with Rezdiffra, several other players are moving in — and how they position themselves will define whether they compete for share or unlock new volume.

Madrigal Pharmaceuticals

Rezdiffra is more than a product — it’s the blueprint. As the first FDA-approved Thr-β agonist for non-cirrhotic MASH (F2–F3), Madrigal has established itself as the default benchmark in both clinical and commercial terms. It’s priced, positioned, and prescribed in a way that shapes the entire treatment ecosystem.

Key strategic advantages:

• Clinical credibility from MAESTRO-NASH with both fibrosis and NASH resolution data

• Label design that avoids biopsy requirement — accelerating real-world adoption

• Payer traction with an implied annualized sales run rate of ~$0.8–1.0 billion just months post-launch

What’s next? Madrigal is doubling down on lifecycle management — combination therapy trials, F4 expansion strategies, and potential outcomes-based contracts. Rezdiffra is not a one-and-done asset; it’s the foundation of a broader liver disease franchise.

 

Viking Therapeutics

VK2809 is the most credible near-term competitor. A liver-targeted prodrug with strong MRI-PDFF fat reduction data (up to 55%), it enters Phase 3 with momentum. Unlike many follow-ons, Viking is not chasing differentiation — it's aiming to match Rezdiffra and position on price, tolerability, or delivery format.

Risks and opportunities:

• Timing is everything — late entry (post-2027) risks narrowing its first-line opportunity

• Efficacy is promising, but fibrosis data is limited compared to Rezdiffra

• If approved, VK2809 is likely to be positioned as a cost-sensitive alternative in select payer environments

In short, Viking is building a solid asset — but without clear differentiation, its upside depends on how the market expands.

 

Terns Pharmaceuticals

TERN-501 is currently in Phase 2. The strategy here is lean and targeted — Terns is aiming to validate the mechanism, build out biomarker correlations, and position as a combo-friendly asset.

Why it matters:

• TERN-501’s likely path is licensing or partnership, not solo commercialization

• Modest competitive pressure — but the asset could scale quickly in combination trials

• Not expected to threaten Rezdiffra’s monotherapy share before 2030

This is a wait-and-watch player. The asset is real. The strategy is still forming.

 

Ascletis Pharma

ASC41 is primarily China-focused and early in Phase 2. While its footprint is regional, it plays an important role in local market shaping — especially in a country where diagnosis rates are low, but prevalence is massive.

Don’t expect ASC41 to compete globally, but do expect it to influence pricing logic and regulatory timelines in Asia-Pacific.

 

Emerging Assets: Aligos & Eccogene

• ALG-055009 (Aligos Therapeutics) and ECC4703 (Eccogene) are in Phase 1 or preclinical stages

• Their timelines place them well beyond 2030 for meaningful revenue impact

• Both may serve as platform assets for combination regimens rather than standalone therapy

 

Competitive Benchmarking Takeaways

Company	Asset	Stage	Global Strategy	Commercial Threat (to Rezdiffra)
Madrigal	Rezdiffra	Approved	Global anchor, full label	N/A (current market leader)
Viking	VK2809	Phase 3	Monotherapy alt., cost play	Moderate post-2027
Terns	TERN-501	Phase 2	Combo-oriented	Low near-term
Ascletis	ASC41	Phase 2	China-focused	None globally
Aligos, Eccogene	Early stage	Phase 1	TBD	Long-dated entry

 

Expert Insight: The near-term competitive set remains most relevant in thyroid hormone receptor beta (THR-β) agonists and adjacent metabolic mechanisms, with Viking’s VK2809 representing the most credible medium-term commercial pressure due to late-stage positioning and a potential monotherapy + pricing narrative. Mid-stage assets (e.g., TERN-501) skew toward combination strategies and are less likely to disrupt near-term share capture, while regionally constrained programs (e.g., ASC41) limit global threat. Early-stage entrants should be monitored for mechanism novelty or differentiated safety, but are unlikely to materially impact Rezdiffra before the late 2020s.

 

REGIONAL LANDSCAPE AND ADOPTION OUTLOOK

Market size alone doesn’t define the opportunity in Thr-β agonists — diagnostic reach, reimbursement readiness, and fibrosis staging infrastructure do. That’s why growth patterns vary sharply by region. Some countries are unlocking commercial value quickly. Others have the patients, but not the pathway.

North America

The U.S. is the commercial engine of the Thr-β market, both in launch-phase revenue and near-term scalability. As of mid-2025, Rezdiffra is already generating $212.8 million in quarterly net sales, translating to a $0.8–1.0 billion annualized run rate.

What makes the U.S. so primed?

• ~4 million diagnosed MASH patients, including ~1.4 million in F2–F3 fibrosis stages

• High specialist density (GI and hepatology) with prescribing authority

• Fast adoption of non-invasive diagnostics (NITs), reducing reliance on liver biopsy

• Payer structures that support step-edits but are not overly restrictive

Canada shares structural similarities but lags in NIT integration and payer agility. That said, it’s expected to mirror U.S. growth patterns by 2027–2028.

Bottom line: Rezdiffra’s U.S. launch validated commercial demand. The rest of the market will use this playbook — if they can match the infrastructure.

 

Europe (EU5 + UK)

Europe has strong prevalence (~12–15 million MASH) and ~3 million diagnosed patients, but uptake is gated by public health timelines and reimbursement frameworks.

• Germany, France, and the UK are the fastest movers — with HTA reviews already underway

• Italy and Spain show demand but suffer from delayed diagnostic adoption and regional funding gaps

• Diagnostic infrastructure is improving, but biopsy is still more commonly used than in the U.S.

• The European Society for the Study of the Liver (EASL) is pushing for updated guidelines to promote NIT-based eligibility

In short, Europe will unlock real volume — but over time, not overnight. Expect meaningful contribution to market size starting 2027 onward, after HTA approvals and broader NIT coverage.

 

Asia-Pacific

The region is split between high-potential markets like Japan and structurally constrained giants like China.

Japan

• Lower overall MASH prevalence (~2–3 million)

• Exceptionally high diagnosis and fibrosis staging accuracy

• Reimbursed access likely by 2027

• Strong clinical uptake expected in urban tertiary centers

China

• Tens of millions of MASH cases — the largest raw opportunity

• Diagnosis rates remain extremely low

• Structural access barriers: limited NIT penetration, few trained specialists, and weak reimbursement

• Expected to remain commercially negligible through 2030 unless major public health shifts occur

India, South Korea, Southeast Asia

• High prevalence, moderate diagnosis

• Rapid expansion of private hospital networks with early NIT adoption

• Rezdiffra or competitors could partner with local distributors post-2028

To be honest, APAC is where scale lives — but only Japan is currently where revenue lives.

 

Latin America, Middle East & Africa (LAMEA)

This region is still early-stage from a market access standpoint, but the growth drivers are starting to show.

• Brazil and Mexico are leading Latin America, with rising urban diagnostic access and government support

• Saudi Arabia and UAE are building advanced children’s and liver-focused hospitals — a longer-term funnel for Thr-β agents

• Sub-Saharan Africa remains commercially out of scope, with almost no NIT access and very low MASH diagnosis rates

The common threads: affordability constraints, low biopsy/NIT availability, and heavy dependence on public sector investment. Still, public-private partnerships and NGO-funded screening programs may create localized revenue pockets by 2030.

 

Regional Revenue Outlook Summary (2025–2030)

The regional revenue outlook for 2025–2030 highlights a market that remains anchored in North America, while Europe and Asia-Pacific show accelerating momentum driven by policy pathways, adoption curves, and expanding care delivery models. LAMEA remains smaller but presents targeted growth pockets where public-private initiatives are increasing investment and access.

Region	2025 Revenue Contribution	2030 Outlook	Key Driver
North America	Dominant (>60%)	Still largest	Diagnosis, payer alignment
Europe	Moderate (~15%)	Growing (~20–25%)	HTA approvals, NIT rollout
Asia-Pacific	Low (~5%)	Accelerating (10–15%)	Japan adoption, emerging private care
LAMEA	Minimal (<3%)	Niche (~5%)	Public-private investment

 

Expert Insight: The revenue mix suggests a “maturity-to-expansion” pattern—North America remains the demand anchor, while Europe’s policy-driven scale-up and Asia-Pacific’s adoption curve (notably Japan and private-care expansion) increasingly shape incremental growth through 2030.

 

This market doesn’t follow GDP or population size. It follows diagnosis infrastructure and payer logic. And that means volume ≠ value — unless the system is wired to identify and treat.

 

END-USER DYNAMICS AND USE CASE

Unlike most chronic therapy classes, Thr-β agonists aren’t prescribed everywhere by everyone. Uptake is highly centralized — concentrated in specialist clinics, liver-focused health systems, and research-heavy tertiary centers. The key dynamic across all settings? End users are less concerned with what the drug is, and more focused on who qualifies and how fast they can be treated.

 

Hepatology and Gastroenterology Clinics

These are the frontline prescribers and account for the majority of early Rezdiffra adoption. Most F2–F3 MASH patients are funneled through these clinics after risk stratification by primary care or endocrinologists.

Typical profile:

• Specialists already familiar with NASH trial data

• Have access to non-invasive tests (FibroScan, MRI-PDFF)

• Work closely with payers or prior authorization teams

• Comfortable initiating therapy without biopsy (if allowed)

For these users, time-to-treatment is critical. Delays in NIT access or payer approvals directly suppress uptake. These clinics also drive early real-world evidence, which pharma companies increasingly rely on to expand labeling and defend pricing.

 

Metabolic and Endocrinology Practices

This group is emerging as a key second-tier prescriber — especially as Thr-β agonists address lipid and metabolic abnormalities alongside liver fat. Endocrinologists managing type 2 diabetes or dyslipidemia often encounter undiagnosed MASH.

Why they matter:

• Can serve as a referral engine or even a primary prescriber in integrated systems

• Tend to adopt combination therapy logic early (GLP-1s + Thr-β)

• Their inclusion expands the funnel beyond liver specialists

However, prescribing volume remains low today. Most endocrinologists still refer to hepatologists for fibrosis confirmation — a bottleneck unless more automated NIT workflows are adopted.

 

Tertiary Hospitals and Academic Medical Centers

These institutions act as testing grounds for complex cases, often managing F3 patients at high risk of progression. They also house the infrastructure needed for:

• Advanced diagnostics (elastography, functional MRI)

• Cross-disciplinary care teams (cardio-metabolic + hepatology)

• Pediatric MASH research (where off-label interest is growing)

They’re also critical in generating health economics data that influences public payer decisions — particularly in Europe and Japan.

 

Community Health Networks and Large IDNs (Integrated Delivery Networks)

In the U.S., large IDNs and community health systems are slowly adopting Thr-β prescribing, especially for patients previously lost in the diagnostic pipeline. But their operational limitations can delay adoption:

• NIT access is inconsistent

• Workflow integration with primary care is still evolving

• Prior authorization adds friction for lower-income populations

That said, once streamlined, IDNs offer scale at speed. A single payer-aligned protocol update could trigger dozens of clinics to begin prescribing within a system.

 

Use Case Highlight: Multi-Specialty Clinic Network (U.S. Midwest)

A regional health system operating 30+ multi-specialty clinics faced a sharp rise in diagnosed MASH cases after launching a NIT screening program tied to annual diabetes checkups.

Within six months:

• Fibrosis staging increased 3x

• ~1,500 F2–F3 patients were identified as Rezdiffra-eligible

• The health system initiated a standing order protocol allowing endocrinologists to start therapy post-NIT, without hepatology referral

• Payer approval rates rose after documentation templates were standardized

The result? Over 400 patients started on therapy in the first rollout quarter, reducing bottlenecks, increasing persistence, and generating payer interest in outcomes-based contracts.

 

RECENT DEVELOPMENTS + OPPORTUNITIES & RESTRAINTS

Recent Developments (2024–2025)

• Rezdiffra received FDA approval in early 2024, marking the first pharmacologic approval for non-cirrhotic MASH patients with F2–F3 fibrosis — effectively creating the global Thr-β agonist category.

• Rezdiffra launch metrics exceeded early projections, with ~23,000 patients initiated in a single quarter and quarterly net sales reaching $212.8 million by mid-2025.

• VK2809 completed its Phase 2b VOYAGE trial, showing up to 55% liver fat reduction and preparing for Phase 3 initiation in 2025.

• Terns Pharmaceuticals advanced TERN-501 through Phase 2a, signaling early intent to position in combination therapy or as a licensing candidate.

• Global payers in the U.S. and Europe updated prior authorization criteria, enabling biopsy-free initiation of Thr-β therapy based on non-invasive test (NIT) confirmation — a major step in reducing friction to access.

 

Opportunities

• Rapid non-invasive diagnostic adoption is expanding the eligible patient pool in developed markets — particularly through FibroScan and MRI-PDFF integration in primary care.

• Combination therapy development is opening doors to dual-mechanism regimens, particularly pairing Thr-β agonists with GLP-1s or PPAR agents for broader metabolic coverage.

• Global reimbursement momentum is accelerating, with Japan, Germany, and the UK advancing HTA reviews that could unlock substantial new market access by 2027.

• Outcomes data from Rezdiffra’s ongoing trials could validate use in F4 fibrosis patients and drive label expansion — shifting the market from moderate fibrosis to advanced liver disease segments.

 

Restraints

• Diagnosis remains the primary bottleneck, with over 70% of global MASH patients still undiagnosed and most health systems lacking automated staging workflows.

• China and other emerging markets remain commercially constrained, not due to lack of need, but due to limited NIT access, payer support, and specialist infrastructure.

• Market education among primary care and endocrinologists is uneven, delaying referral and treatment initiation even in eligible patients.

 

7.1. Report Coverage Table

Report Attribute	Details
Forecast Period	2025 – 2035
Market Size Value in 2025	USD <1.0 Billion
Revenue Forecast in 2030	USD ~11.0 Billion
Overall Growth Rate	Robust CAGR through 2030
Base Year for Estimation	2024
Historical Data	2019 – 2023
Unit	USD Billion, CAGR (2025 – 2035)
Segmentation	By Fibrosis Stage, By Diagnosis Pathway, By Treatment Setting, By Geography
By Fibrosis Stage	F2 MASH, F3 MASH
By Diagnosis Pathway	Biopsy-Confirmed, NIT-Confirmed
By Treatment Setting	Rezdiffra Monotherapy, Combination Therapy
By Region	North America, Europe, Asia-Pacific, LAMEA
Country Scope	United States, Germany, France, United Kingdom, Japan, China
Market Drivers	- First-in-class therapy for F2–F3 MASH - Rapid adoption of non-invasive diagnostics - Strong payer momentum in high-income regions
Customization Option	Available upon request