Graves Orbitopathy - Market Insight, Epidemiology, and Market Forecast - 2034

Key Highlights:

• According to DelveInsight's estimates, in 2023, there were approximately 1.5 million diagnosed prevalent cases of Graves' orbitopathy in the 7MM. Of these, the United States accounted for 44% of the cases, while EU4 and the UK accounted for nearly 49% and Japan represented 7% of the cases, respectively.
• The Graves' orbitopathy market is projected to see consistent growth, with a robust compound annual growth rate (CAGR) anticipated from 2024 to 2034. This expansion across the 7MM will be driven by the introduction of innovative therapies, including VRDN-001, VRDN-003, lonigutamab, and efgartigimod PH20, among others. Furthermore, increasing cases of Graves' orbitopathy, influenced by factors such as smoking, age, the duration of hyperthyroidism, radioactive iodine treatment, genetics, and environmental elements like selenium deficiency and stress, will further support the market's growth.
• According to DelveInsight's analysis, the Graves' orbitopathy market in the 7MM was valued at approximately USD 2,340.6 million in 2023. Over the forecast period from 2024 to 2034, this market is projected to grow at a CAGR of 17.7%.
• Graves' orbitopathy has limited treatment options, with TEPEZZA as the only approved drug. The disease's complex autoimmune nature and varied clinical manifestations make developing targeted, disease-modifying therapies challenging, leaving a significant unmet need for more effective treatments.
• Viridian Therapeutics, ACELYRIN, Argenx, and Immunovant Sciences, among others are progressing their assets through various clinical trial phases, driving innovation in the Graves' orbitopathy market and creating significant growth opportunities.
• Viridian Therapeutics' VRDN-003, an IGF-1R antibody, is currently in Phase III clinical development, with a Biologics License Application (BLA) submission for Graves' orbitopathy treatment expected by the end of 2026 in the US.

DelveInsight's "Graves' Orbitopathy - Market Insights, Epidemiology, and Market Forecast - 2034" report delivers an in-depth understanding of Graves' orbitopathy, historical and forecasted epidemiology, as well as the Graves' orbitopathy market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

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

Graves' Orbitopathy Understanding and Treatment Algorithm

Graves' orbitopathy overview

Graves' orbitopathy, also known as Thyroid Eye Disease, is the most common extrathyroidal manifestation of Graves' disease and results from autoimmune activity causing orbital inflammation. Autoantibodies, likely targeting a shared protein in the orbit and thyroid, drive this condition, which progresses through an early active stage and a late inactive stage, classified by severity and its impact on vision and quality of life.

Symptoms range from eye irritation, redness, and swelling to advanced complications like optic nerve compression and vision loss. Key risk factors include stress, smoking, and poorly controlled hyperthyroidism, while pathologic changes include glycosaminoglycan deposition, inflammation, fibrosis, and fat accumulation in the orbit, leading to proptosis and impaired ocular motility.

Graves' orbitopathy diagnosis

Diagnosing Graves' orbitopathy may involve imaging studies such as CT scans or MRI to detect changes in the eye muscles, along with blood tests to evaluate thyroid hormone levels and antibodies for abnormalities.

Graves' orbitopathy treatment

The management of Graves' orbitopathy varies based on symptom severity and includes medical, surgical, and fundamental treatments aimed at reducing visual complications, minimizing side effects, and preventing disease progression or recurrence. While no preventive therapy exists, corticosteroids administered for three months may reduce orbitopathy risks following radioactive iodine therapy. Botulinum toxin can temporarily address dysthyroid strabismus during the acute phase.

Graves' Orbitopathy Epidemiology

As the market is derived using a patient-based model, the Graves' orbitopathy epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by total diagnosed prevalent cases of Graves' orbitopathy, gender-specific diagnosed prevalent cases of Graves' orbitopathy, chronicity-specific diagnosed prevalent cases of Graves' orbitopathy, and severity-specific diagnosed prevalent cases of acute Graves' orbitopathy in the 7MM covering the United States, EU4 countries (Germany, France, Italy, and Spain) and the United Kingdom, and Japan from 2020 to 2034.

• DelveInsight estimates that in 2023, there were around 7.1 million prevalent cases of Graves' disease across the 7MM, with 3.7 million being diagnosed. This number is projected to rise by 2034.
• In 2023, the US recorded the highest number of diagnosed prevalent cases of Graves' orbitopathy, with approximately 643 thousand cases, a figure anticipated to grow over the study period (2020-2034).
• In 2023, Germany reported the highest number of diagnosed prevalent cases of Graves' orbitopathy among the EU4 and the UK, with approximately 162 thousand cases, followed by France with around 149 thousand cases. In contrast, Spain had the lowest number, with about 128 thousand cases.
• In 2023, Japan reported approximately 102 thousand diagnosed prevalent cases of Graves' orbitopathy.
• In 2023, the US reported nearly 129 thousand diagnosed prevalent cases of Graves' orbitopathy in males and 514 thousand cases in females.
• In 2023, the EU4 and the UK reported nearly 204 thousand acute cases and 523 thousand chronic cases of Graves' orbitopathy.
• In 2023, Japan reported nearly 20 thousand mild, 7 thousand moderate to severe, and 14 hundred sight-threatening cases of acute Graves' orbitopathy.

Graves' Orbitopathy Drug Chapters

The drug chapter segment of the Graves' orbitopathy report encloses a detailed analysis of Graves' orbitopathy-marketed drugs and mid to late-stage (Phase III and Phase II) pipeline drugs. It also helps understand the Graves' orbitopathy clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug, and the latest news and press releases.

Marketed Drugs

TEPEZZA (teprotumumab-Trbw): Amgen (Horizon Therapeutics)

TEPEZZA, an IGF-1R inhibitor and fully human IgG1 monoclonal antibody produced in CHO-DG44 cells, has a molecular weight of approximately 148 kDa. It is currently being studied in Phase III trials for moderate-to-severe active Graves' orbitopathy and chronic Thyroid Eye Disease (TED) with a low Clinical Activity Score (CAS). Amgen is also investigating the potential for subcutaneous administration. TEPEZZA has received Breakthrough Therapy and Fast Track designations from the US FDA for Graves' orbitopathy treatment, along with orphan drug designations in both the US and Japan. It has regulatory approval in the US and Japan for active Graves' orbitopathy. In April 2024, Amgen announced plans to submit a Marketing Authorization Application for teprotumumab to the European Medicines Agency.

Emerging Drugs

VRDN-003: Viridian Therapeutics

VRDN-003 is a subcutaneously administered anti-IGF-1R antibody in development for TED, designed to have a longer half-life and act as a full IGF-1R antagonist. It shares the same binding domain as VRDN-001 and targets the clinically validated IGF-1R inhibition mechanism. Viridian launched two Phase III trials, REVEAL-1 and REVEAL-2, for active and chronic TED, respectively, evaluating VRDN-003 administered every 4 or 8 weeks versus placebo. Topline data is expected in 2026, with a BLA submission by year-end. Positive results from the THRIVE-2 trial further support confidence in VRDN-003's success announced in December 2024.

Efgartigimod PH20 SC: Argenx

Efgartigimod PH20 SC, an investigational drug developed by Argenx, is designed to treat TED. This fully human antibody fragment targets the neonatal Fc receptor (FcRn), blocking its function to reduce pathogenic immunoglobulin G (IgG) autoantibodies, which are implicated in autoimmune diseases.

Currently in Phase III proof-of-concept development for TED, the subcutaneous formulation (PH20 SC) is intended to enhance the drug's dispersion and absorption, potentially improving both efficacy and patient convenience.

Lonigutamab: ACELYRIN

Lonigutamab is an SC-delivered humanized IgG1 monoclonal antibody targeting IGF-1R for the treatment of TED. ACELYRIN recently concluded a positive end-of-Phase II meeting with the US FDA, aligning on critical elements of the Phase III program, including trial size, endpoints, and dose selection. A webcast will be held in early 2025 to review the Phase II results and FDA feedback.

In August 2024, despite strong clinical performance of izokibep, ACELYRIN shifted its focus to lonigutamab, resulting in a 33% workforce reduction. The company plans to initiate Phase IIb/III trials in late 2024, with Phase III starting in 2025 and topline results expected in 2026.

Drug Class Insights

Treatment for Graves' orbitopathy includes supportive measures and specific therapies based on disease severity. Supportive care consists of ocular lubrication, eye patches, prism correction for diplopia, and head-of-bed elevation to alleviate swelling. Pharmacological treatments include glucocorticoids, mycophenolate, rituximab, tocilizumab, teprotumumab, and cyclosporine/mTOR inhibitors. Oral prednisone is commonly used, with higher doses or intravenous administration for optic nerve compression. Emerging therapies, such as VRDN-001, VRDN-003, batoclimab, efgartigimod PH20 SC, ENSPRYNG, LASN01, linsitinib, AMG 732, and lonigutamab, aim to enhance treatment outcomes and address unmet needs.

Batoclimab (IMVT-1401) and efgartigimod PH20 SC target the neonatal Fc receptor (FcRn) to reduce pathogenic IgG autoantibodies. Batoclimab, a fully human monoclonal antibody, is delivered as a subcutaneous injection and developed for various IgG-mediated autoimmune diseases, including Graves' disease. Efgartigimod, a human antibody fragment, is also available in subcutaneous form and designed to improve dispersion and absorption, focusing on thyroid eye disease. Both therapies aim to reduce IgG levels, with differences in formulation and pharmacokinetics offering potential patient convenience benefits.

Market Outlook

Graves' orbitopathy treatment strategies are divided into supportive and specific approaches, based on disease severity. Supportive care includes ocular lubrication, eye patches, prism correction for diplopia, and head-of-bed elevation to reduce swelling. Pharmacological treatments involve glucocorticoids, mycophenolate, rituximab, tocilizumab, teprotumumab, and cyclosporine/mTOR inhibitors. Corticosteroids, especially oral prednisone, are the mainstay, with higher doses or intravenous administration used for optic nerve compression.

TEPEZZA (teprotumumab), an IGF-1R inhibitor, gained US FDA approval in 2020 as a fully human IgG1 monoclonal antibody produced in Chinese hamster ovary (CHO-DG44) cells, with a molecular weight of 148 kDa. In 2024, Japan's Ministry of Health, Labour, and Welfare (MHLW) approved it for active Graves' orbitopathy, expanding its global use. Other treatments, such as methotrexate, azathioprine, intravenous immunoglobulins, and anti-tumor necrosis factor therapies (e.g., adalimumab, etanercept, infliximab), show limited efficacy compared to biological agents like teprotumumab and rituximab.

Currently, TEPEZZA is the only approved therapy for active Graves' orbitopathy, highlighting a major unmet need. Off-label treatments like glucocorticoids, rituximab, and tocilizumab have inconsistent efficacy and no regulatory approval for this condition. This gap emphasizes the need for targeted, effective therapies, especially for severe or refractory cases.

Recent advancements include VRDN-001, VRDN-003, batoclimab, efgartigimod PH20 SC, ENSPRYNG (satralizumab, RG6168), LASN01, linsitinib, AMG 732 (formerly HZN-280), and lonigutamab (anti-IGF-1R), which aim to improve treatment outcomes and address unmet needs.

• The total market size of Graves' orbitopathy in the 7MM was approximately USD 2,340.6 million in 2023 and is projected to increase during the forecast period (2024-2034).
• The market size for Graves' orbitopathy in the US was approximately USD 2,114.5 million in 2023 and is anticipated to increase due to the launch of emerging therapies.
• The total market size of EU4 and the UK was calculated to be approximately USD 203.7 million in 2023, which was nearly 9% of the total market revenue for the 7MM.
• In 2023, Germany dominated the market among EU4 and the UK, generating around USD 45.4 million. France followed closely with approximately USD 41.8 million, while the UK recorded around USD 40.8 million.
• In 2023, the total market size of Graves' orbitopathy was approximately USD 22.3 million in Japan which is anticipated to increase during the forecast period (2024-2034).
• Estimates suggest that VRDN-003 is expected to generate approximately USD 1,473.1 million in the 7MM by 2034.

Graves' orbitopathy Drugs Uptake

This section focuses on the uptake rate of potential drugs expected to be launched in the market during 2020-2034.

Graves' orbitopathy 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.

Pipeline development activities

The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for emerging therapies for Graves' orbitopathy.

KOL Views

To keep up with current market trends, we take KOLs and SMEs' opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry Experts contacted for insights on Graves' orbitopathy evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, and drug uptake, along with challenges related to accessibility, including Medical/scientific writers, Medical Professionals, Professors, Directors, and Others.

DelveInsight's analysts connected with 50+ KOLs to gather insights; however, interviews were conducted with 15+ KOLs in the 7MM. Centers like the Cedars-Sinai Medical Center, US, Stanford Department of Ophthalmology, US, Center for Drug Evaluation and Research, US, Johannes Gutenberg University, Germany, Nantes University Hospital, France, University of Insubria, Italy, Hospital Universitario y Politecnico La Fe, Spain, University Hospitals Bristol NHS Foundation Trust, UK, and Ito Hospital, Shibuya-ku, Japan, among others, were contacted. Their opinion helps understand and validate current and emerging therapy treatment patterns or Graves' orbitopathy market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

Physician's View

As per the KOLs from the US, Thyroid Eye Disease (TED) starts with orbital and periocular inflammation, progressing to a chronic phase with persistent symptoms. Active TED, marked by a Clinical Activity Score (CAS), involves pain, swelling, redness, proptosis, and, in severe cases, diplopia. In the US, TED prevalence ranges from 0.16% to 0.25%, with higher risk in males, individuals over 65, tobacco users, and those with elevated thyroid autoantibodies.

As per the KOLs from France, Graves' orbitopathy, the most common extra-thyroid complication of Graves' disease, can be severe and requires multidisciplinary care based on clinical activity and severity. Diagnosis and management should involve an ophthalmologist, endocrinologist, and, if needed, a surgeon specializing in orbital pathologies, such as a maxillofacial surgeon, ENT specialist, or neurosurgeon.

As per the KOLs from Japan, despite its impact on social and psychological well-being, epidemiological data on TED in Japan is limited. Current estimates suggest a prevalence of 24.65-37.58 per 100,000 people, highlighting a potential gap in awareness and diagnosis within the population.

Qualitative Analysis

We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT and Conjoint 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.

Conjoint Analysis analyzes multiple emerging therapies based on relevant attributes such as safety, efficacy, frequency of administration, route of administration, and order of entry. Scoring is given based on these parameters to analyze the effectiveness of therapy.

To analyze the effectiveness of these therapies, have calculated their attributed analysis by giving them scores based on their ability to improve atrial and ventricular dimension/function and ability to regulate heart rate.

Further, the therapies' safety is evaluated wherein the adverse events are majorly observed, and it sets a clear understanding of the side effects posed by the drug in the trials, which directly affects the safety of the molecule in the upcoming trials. It sets a clear understanding of the side effects posed by the drug in the trials. In addition, the scoring is also based on the route of administration, order of entry and designation, probability of success, and the addressable patient pool for each therapy. According to these parameters, the final weightage score and the ranking of the emerging therapies are decided.

Market Access and Reimbursement

Horizon Commercial Copay Program

Horizon is committed to ensuring that patients pay the lowest possible amount for their medications. Eligible patients may qualify for a USD 0 copay, covering both the medication and intravenous infusion costs.

To be eligible for the Horizon Commercial Copay Program, patients must meet the following criteria:

• The prescription cannot be covered, in part or in full, by any government-funded program, including but not limited to Medicare, Medicare Part D, Medicaid, Medigap, VA, CHAMPUS, Department of Defense (DoD), TRICARE, or any state, patient foundation, or other pharmaceutical assistance program.
• The patient must be prescribed a Horizon rare disease medication for an FDA-approved indication, as specified in the prescribing information.
• The patient must reside in the US.
• The patient must have commercial insurance and be financially responsible for a portion of the medication and/or infusion costs, if applicable

The report provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenarios, 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 Graves' orbitopathy, explaining its causes, signs and symptoms, pathogenesis, and currently available therapies.
• Comprehensive insight into the epidemiology segments and forecasts, the future growth potential of diagnosis rate, disease progression, and treatment guidelines 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 treatment landscape.
• A detailed review of the Graves' orbitopathy 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 and expert insights/KOL views, patient journey, and treatment preferences that help shape and drive the 7MM Graves' orbitopathy market.

Graves' orbitopathy report insights

• Patient Population
• Therapeutic Approaches
• Graves' orbitopathy Pipeline Analysis
• Graves' orbitopathy Market Size and Trends
• Existing and Future Market Opportunity

Graves' orbitopathy report key strengths

• 11 years Forecast
• The 7MM Coverage
• Graves' orbitopathy Epidemiology Segmentation
• Key Cross Competition
• Attribute analysis
• Drugs Uptake and Key Market Forecast Assumptions

Graves' orbitopathy report assessment

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

Key Questions:

Market Insights

• What was the total market size of Graves' orbitopathy, the market size of Graves' orbitopathy by therapies, and market share (%) distribution in 2020, and what would it look like by 2034? What are the contributing factors for this growth?
• How will VRDN-003 affect the treatment paradigm of Graves' orbitopathy?
• How will TEPEZZA compete with other upcoming products and marketed therapies?
• Which drug is going to be the largest contributor by 2034?
• What are the pricing variations among different geographies for approved and marketed therapies?
• How would future opportunities affect the market dynamics and subsequent analysis of the associated trends?

Epidemiology Insights

• What are the disease risks, burdens, and unmet needs of Graves' orbitopathy? What will be the growth opportunities across the 7MM with respect to the patient population pertaining to Graves' orbitopathy?
• What is the historical and forecasted Graves' orbitopathy patient pool in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan?
• Out of the countries mentioned above, which country would have the highest diagnosed prevalent Graves' orbitopathy population during the forecast period (2024-2034)?
• What factors are contributing to the growth of Graves' orbitopathy cases?

Current Treatment Scenario, Marketed Drugs, and Emerging Therapies

• What are the current options for the treatment of Graves' orbitopathy? What are the current clinical and treatment guidelines for treating Graves' orbitopathy?
• How many companies are developing therapies for the treatment of Graves' orbitopathy?
• How many emerging therapies are in the mid-stage and late stage of development for treating Graves' orbitopathy?
• What are the recent novel therapies, targets, mechanisms of action, and technologies developed to overcome the limitations of existing therapies?
• What is the cost burden of current treatment on the patient?
• Patient acceptability in terms of preferred treatment options as per real-world scenarios?
• What are the accessibility issues of approved therapy in the US?
• What is the 7MM historical and forecasted market of Graves' orbitopathy?

Reasons to Buy:

• The report will help develop business strategies by understanding the latest trends and changing treatment dynamics driving the Graves' orbitopathy market.
• Insights on patient burden/disease prevalence, evolution in diagnosis, and factors contributing to the change in the epidemiology of the disease during the forecast years.
• Understand the existing market opportunities in varying geographies and the growth potential over the coming years.
• The distribution of historical and current patient share is based on real-world prescription data in the US, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.
• Identifying upcoming solid players in the market will help devise strategies to help get ahead of competitors.
• Detailed analysis and ranking of class-wise potential current and emerging therapies under the conjoint analysis section to provide visibility around leading classes.
• Highlights of Access and Reimbursement policies for Graves' orbitopathy, barriers to accessibility of approved therapy, 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.