Hereditary Transthyretin Amyloidosis - Market Insight, Epidemiology, and Market Forecast - 2034

Key Highlights:

• Hereditary Transthyretin Amyloidosis (hATTR) is a rare, genetic disease where a mutation in the transthyretin (TTR) gene causes abnormal protein deposits called amyloid to build up in various organs, most notably the nerves and heart, leading to progressive damage and symptoms like numbness, tingling, weakness, and heart problems.
• The hATTR can be further sub-divided into familial amyloid polyneuropathy (FAP) and familial amyloid cardiomyopathy (FAC). There are over 120 different mutations in the TTR gene, and each mutation causes a different pattern of disease onset, symptoms and outlook. The most common ATTR mutations such as ATTR V30M variant, ATTR V122I variant, ATTR T60A variant, and others.
• Abdominal fat biopsy is a minimally invasive and safe procedure that can lead to the histological confirmation and typing of amyloid deposits.
• ATTR has several phenotypes including ATTR-cardiomyopathy (CM), which impacts the heart, potentially leading to heart failure, ATTR-polyneuropathy (PN), which affects the peripheral nervous system including the brain, and mixed phenotype, where patients experience symptoms of both.
• In August 2025, Prothena Corporation announced that Novo Nordisk communicated during their second quarter 2025 that they expect to advance coramitug, a potential first-in-class amyloid depleter antibody, into a Phase III program for ATTR amyloidosis with cardiomyopathy (ATTR-CM) in 2025. Coramitug was initially developed by Prothena and was acquired by Novo Nordisk in July 2021.
• Currently treatment armamentarium includes the US FDA approved AMVUTTRA (vutrisiran), ONPATTRO (patisiran), TEGSEDI (inotersen), VYNDAQEL (tafamidis meglumine) and VYNDAMAX (tafamidis), WAINUA (eplontersen), and others.
• Several potential therapies are being investigated for the management of hATTR. The anticipated launch of the promising candidate like Nexiguran ziclumeran, ALXN2220, Coramitug, and others during the forecast period (2025-2034) is expected to bring about a significant shift in the market dynamics of hATTR.

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

The hATTR market report provides current treatment practices, emerging drugs, hATTR share of individual therapies, and current and forecasted hATTR market size from 2020 to 2034, segmented by seven major markets. The report also covers current hATTR treatment practices/algorithms and unmet medical needs to curate the best of the opportunities and assess the underlying potential of the market.

Geography Covered:

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

Hereditary Transthyretin Amyloidosis Understanding and Treatment Algorithm

Hereditary Transthyretin Amyloidosis Overview

Hereditary transthyretin-mediated (hATTR) amyloidosis is a rare, inherited, progressively debilitating disease caused by mutations in the TTR (transthyretin) gene. These mutations lead to the misfolding of transthyretin proteins, which then accumulate as amyloid fibrils in various organs and tissues. The buildup primarily affects the peripheral nerves, heart, and sometimes the gastrointestinal tract. Symptoms vary widely but commonly include progressive peripheral neuropathy (numbness, tingling, pain), autonomic dysfunction (such as dizziness, digestive issues), and cardiomyopathy (leading to shortness of breath, fatigue, and heart failure). If left untreated, hATTR amyloidosis can lead to significant organ damage and is often fatal.

Hereditary Transthyretin Amyloidosis Diagnosis

Diagnosing hereditary transthyretin-mediated (hATTR) amyloidosis can be challenging due to its diverse and often non-specific symptoms. The diagnostic process typically begins with a thorough clinical evaluation, including a family history and assessment of neuropathic and cardiac symptoms. Genetic testing is essential to confirm mutations in the TTR gene, distinguishing hATTR from other forms of amyloidosis. Tissue biopsy with Congo red staining may be used to confirm amyloid deposits, while imaging techniques like echocardiography, cardiac MRI, or nuclear scintigraphy (e.g., Tc-99m-PYP scan) help evaluate cardiac involvement. Blood and urine tests, along with nerve conduction studies, support the diagnosis, and serum/urine immunofixation is used to rule out light-chain (AL) amyloidosis. Early and accurate diagnosis is critical for timely treatment and improved outcomes.

Hereditary Transthyretin Amyloidosis Treatment

Treatment of hereditary transthyretin-mediated (hATTR) amyloidosis focuses on reducing the production or effects of misfolded transthyretin (TTR) protein to slow disease progression and manage symptoms. TTR silencers like patisiran (siRNA) and inotersen or eplontersen (antisense oligonucleotides) reduce TTR protein production in the liver, while tafamidis, a TTR stabilizer, prevents the protein from misfolding. Investigational therapies such as CRISPR-Cas9 gene editing (e.g., nexiguran ziclumeran) aim to permanently inactivate the TTR gene. For patients with advanced cardiac or neurological symptoms, supportive care including pain management, cardiac medications, and mobility support is essential. Early initiation of therapy is crucial to preserving organ function and improving quality of life.

Hereditary Transthyretin Amyloidosis Epidemiology

The hATTR epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by the total prevalent cases of hATTR, total diagnosed prevalent cases of hATTR, type-specific cases of hATTR, stage-specific cases of hATTR, New York Heart Association (NYHA) Classification of Familial Amyloid Cardiomyopathy (FAC) in the 7MM market covering the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan from 2020 to 2034.

• The US accounted for nearly 65% of the total diagnosed prevalent cases of hATTR in the 7MM in 2024, which is expected to increase further by 2034.
• In the United States, the most common variants of hATTR include TTR V30M, TTR T60A, TTR L58H, TTR S77Y, and TTR I84S.
• Around 45% of hATTR cases in the US were specific to familial amyloid polyneuropathy (FAP).
• Hereditary ATTR affects males and females usually with no significant gender prevalence, yet the parent-of-origin effect in carriers is hypothesized because maternal inheritance of the mutation seems to be related to a higher risk of disease. However, in families with late-onset disease, a male predominance.
• Annual incidence of hATTR in Europe is estimated at 0.3 new cases per million people.

Hereditary Transthyretin Amyloidosis Drug Chapters

The drug chapter segment of the hATTR report encloses a detailed analysis of hATTR marketed and emerging pipeline drugs. It also deep dives into hATTR's pivotal clinical trial details, recent and expected market approvals, patent details, the latest news, and recent deals and collaborations.

Currently, AMVUTTRA (vutrisiran), ONPATTRO (patisiran), TEGSEDI (inotersen), VYNDAQEL (tafamidis meglumine) and VYNDAMAX (tafamidis), WAINUA (eplontersen), ATTRUBY (acoramidis) and others are the FDA-approved drugs for treating hATTR. The drug chapter also helps understand the hATTR clinical trial details, expressive pharmacological action, agreements and collaborations, approval, and patent details, and the latest news and press releases.

Marketed Drugs

AMVUTTRA (vutrisiran): Alnylam Pharmaceuticals

AMVUTTRA is a transthyretin (TTR) knockdown agent that works with the body's natural systems to stop TTR protein production and slow the progression of amyloidosis. Reducing the amount of TTR protein produced in the liver leads to fewer harmful amyloid fibrils being deposited in the heart, which causes cardiomyopathy. Amvuttra is administered via injection under the skin every three months in a hospital or clinic. Using Alnylam's Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform, AMVUTTRA is designed for increased potency and high metabolic stability to allow for subcutaneous injection once every three months (quarterly).

• In June 2025, Alnylam Pharmaceuticals announced that The European Commission (EC) has approved an additional indication for AMVUTTRA (vutrisiran), an orphan RNAi therapeutic, for the treatment of wild-type or hereditary transthyretin amyloidosis in adult patients with cardiomyopathy (ATTR-CM).
• In March 2025, Alnylam Pharmaceuticals announced that the US Food and Drug Administration (FDA) has approved for supplemental New Drug Application (sNDA) for its RNAi therapeutic, AMVUTTRA (vutrisiran), for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits.

WAINUA (eplontersen): AstraZeneca/Ionis Pharmaceuticals

WAINUA (eplontersen) is a ligand-conjugated antisense oligonucleotide (LICA medicine designed to reduce the production of transthyretin, or TTR protein. WAINUA has been approved in the US for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults (also referred to as ATTRv-PN). Eplontersen is an antisense oligonucleotide-GalNAc conjugate that causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.

In October 2024, , AstraZeneca and Ionis Pharmaceuticals, announced WAINZUA (eplontersen) has been recommended for approval by the Committee for Medicinal Products for Human Use (CHMP) in the European Union (EU) for the treatment of hereditary transthyretin-mediated amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy, commonly referred to as hATTR-PN or ATTRv-PN.

In December 2023, AstraZeneca and Ionis Pharmaceuticals, announced that US Food and Drug Administration (FDA) has approved WAINUA (eplontersen), for the treatment of polyneuropathy in patients with hereditary transthyretin-mediated amyloidosis (hATTR-PN or ATTRv-PN). Wainua is the only ATTRv-PN treatment approved for self-administration via an auto-injector.

Emerging Therapies

Nexiguran Ziclumeran: Intellia Therapeutics

Nexiguran ziclumeran (nex-z), also known as NTLA-2001, is an investigational in vivo CRISPR-based gene editing therapy being developed by Intellia Therapeutics as a one-time treatment for transthyretin (ATTR) amyloidosis. It is designed to inactivate the TTR gene, which encodes for the transthyretin (TTR) protein. Intellia is leading the development and commercialization of nex-z as part of a collaboration with Regeneron. This is currently in Phase III clinical trials.

In May 2025, Intellia Therapeutics announced positive two-year follow-up data from the ongoing Phase I trial of investigational nexiguran ziclumeran (nex-z) for the treatment of hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN).

In April 2025, Intellia Therapeutics, announced the first patient has been dosed in MAGNITUDE-2, a global, pivotal Phase III trial of nexiguran ziclumeran (nex-z) for the treatment of hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN).

ALXN2220 (formerly NI006): Neurimmune/Alexion Pharmaceuticals

ALXN2220 (formerly NI006) is a human antibody that exclusively targets with high affinity the disease-associated amyloid conformation but not physiological forms of transthyretin. ALXN2220 targets both wild-type ATTR as well as ATTR mutants that are linked to hereditary forms of ATTR cardiomyopathy (ATTR-CM) and ATTR polyneuropathy.

In October 2024, Neurimmune announced that the US FDA granted Fast Track designation to Alexion, AstraZeneca Rare Disease for the development of ALXN2220 (formerly NI006) to treat transthyretin amyloidosis with cardiomyopathy (ATTR-CM).

In April 2024, Neurimmune announced that its partner, Alexion (AstraZeneca's rare disease group), has begun the Phase III DepleTTR-CM clinical study. The study will evaluate the effectiveness and safety of ALXN2220 (formerly NI006) for treating transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) (NCT06183931).

Drug Class Insight

CRISPR-Cas9 gene editing

CRISPR-Cas9 gene editing is a revolutionary genome-editing technology that allows for precise, targeted changes to DNA within living cells. It works by using a guide RNA to direct the Cas9 enzyme to a specific sequence in the genome, where Cas9 makes a double-stranded break in the DNA. The cell then attempts to repair this break, often leading to gene disruption or, if a repair template is provided, gene correction or insertion. Nexiguran Ziclumeran is an investigational, in vivo CRISPR-Cas9 gene-editing therapy designed to treat hereditary transthyretin-mediated (hATTR) amyloidosis by directly targeting the root cause of the disease. It uses a guide RNA to direct the Cas9 enzyme to the TTR gene in liver cells, where Cas9 introduces a double-stranded break in the DNA.

Hereditary Transthyretin Amyloidosis (hATTR) Market Outlook

Treatment strategies for hereditary transthyretin-mediated (hATTR) amyloidosis are increasingly diverse and target various stages of the disease process. Gene silencers, such as eplontersen (WAINUA), patisiran (ONPATTRO), and inotersen (TEGSEDI), work by targeting the TTR mRNA in the liver, significantly reducing the production of both mutant and wild-type transthyretin protein. This slows disease progression by lowering circulating TTR levels. TTR stabilizers, like tafamidis (VYNDAQEL/VYNDAMAX), bind to the TTR protein and prevent it from misfolding into amyloid fibrils, thereby delaying organ damage, particularly in the heart. While there are no approved treatments specifically for degrading amyloid fibrils already deposited in tissues, this area is under investigation, and some therapies may offer indirect benefit. Liver transplantation, historically used to eliminate the primary source of mutant TTR production, is now rarely pursued due to the advent of effective pharmacologic therapies. A promising frontier is gene-editing, exemplified by Nexiguran Ziclumeran, an in vivo CRISPR-Cas9-based therapy that permanently disrupts the TTR gene in liver cells, potentially offering a one-time, curative approach. Alongside these disease-modifying therapies, symptom management and supportive care remain crucial, addressing complications like peripheral neuropathy, autonomic dysfunction, and cardiomyopathy, which are hallmarks of hATTR and contribute significantly to patient morbidity and reduced quality of life.

Hereditary Transthyretin Amyloidosis (hATTR) Drugs Uptake

This section focuses on the uptake rate of potential drugs expected to be launched in the market during 2025-2034. The landscape of hATTR treatment has experienced a profound transformation with the uptake of novel medicines. These innovative therapies are redefining standards of care.

Hereditary Transthyretin Amyloidosis (hATTR) Pipeline Development Activities

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

Pipeline Development Activities

The report covers detailed information on collaborations, acquisitions and mergers, licensing, and patent details for hATTR emerging therapies.

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. Some of the leaders like MD, Professors, Directors, PhD, and others. Their opinion helps to understand and validate current and emerging therapies and treatment patterns or hATTR market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

DelveInsight's analysts connected with 15+ KOLs to gather insights; however, interviews were conducted with 5+ KOLs in the 7MM. Centers such as the University of Florida, Virginia Commonwealth University etc. were contacted. Their opinion helps understand and validate hATTR epidemiology and market trends.

Qualitative Analysis

We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT analysis and Conjoint Analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of gaps in disease diagnosis, patient awareness, physician acceptability, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided.

Conjoint Analysis analyzes multiple approved and 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.

In efficacy, the trial's primary and secondary outcome measures are evaluated; for instance, in event-free survival, one of the most important primary outcome measures is event-free survival and overall survival.

Further, the therapies' safety is evaluated wherein the acceptability, tolerability, and adverse events are majorly observed, and 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 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

Reimbursement may be referred to as the negotiation of a price between a manufacturer and a payer that allows the manufacturer access to the market. It is provided to reduce the high costs and make the essential drugs affordable. Health technology assessment (HTA) plays an important role in reimbursement decision-making and recommending the use of a drug. These recommendations vary widely throughout the seven major markets, even for the same drug. In the US healthcare system, both Public and Private health insurance coverage are included. Also, Medicare and Medicaid are the largest government-funded programs in the US. The major healthcare programs, including Medicare, Medicaid, Health Insurance Program (CHIP), and the state and federal health insurance marketplaces, are overseen by the Centers for Medicare & Medicaid Services (CMS). Other than these, Pharmacy Benefit Managers (PBMs) and third-party organizations that provide services and educational programs to aid patients are also present.

The report further provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenario of currently used 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 descriptive overview of Hereditary Transthyretin Amyloidosis (hATTR), explaining its causes, signs and symptoms, pathogenesis, and currently available therapies.
• Comprehensive insight has been provided into Hereditary Transthyretin Amyloidosis (hATTR) epidemiology and treatment.
• Additionally, an all-inclusive account of both the current and emerging therapies for Hereditary Transthyretin Amyloidosis (hATTR) is provided, along with the assessment of new therapies, which will have an impact on the current treatment landscape.
• A detailed review of the Hereditary Transthyretin Amyloidosis (hATTR) market; historical and forecast is included in the report, covering the 7MM drug outreach.
• The report provides an edge while developing business strategies, by understanding trends shaping and driving the 7MM Hereditary Transthyretin Amyloidosis (hATTR) market.

Hereditary Transthyretin Amyloidosis (hATTR) Report Insights

hATTR Report Insights

• Patient Population
• Therapeutic Approaches
• hATTR Pipeline Analysis
• hATTR Market Size and Trends
• Market Opportunities
• Impact of Upcoming Therapies

hATTR Report Key Strengths

• Ten Years Forecast
• 7MM Coverage
• hATTR Epidemiology Segmentation
• Key Cross Competition
• Highly Analyzed Market
• Drugs Uptake

hATTR Report Assessment

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

FAQs:

• What was the hATTR market share (%) distribution in 2024 and what it would look like in 2034?
• What would be the hATTR total market size as well as market size by therapies across the 7MM during the study period (2020-2034)?
• What are the key findings about the market across the 7MM and which country will have the largest hATTR market size during the study period (2020-2034)?
• What would be the hATTR market growth till 2034?
• What are the disease risks, burdens, and unmet needs of hATTR?
• What is the historical hATTR patient pool in the United States, EU4 (Germany, France, Italy, and Spain), and the UK, and Japan?
• What will be the growth opportunities across the 7MM concerning the patient population of hATTR?
• At what CAGR the population is expected to grow across the 7MM during the study period (2020-2034)?
• How many emerging therapies are in the mid-stage and late stage of development for the treatment of hATTR?
• What are the key collaborations (industry-industry, industry-academia), Mergers and acquisitions, and licensing activities related to hATTR therapies?
• What are the key designations that have been granted for the emerging therapies for hATTR?

Reasons to buy:

• The report will help in developing business strategies by understanding trends shaping and driving the hATTR market.
• To understand the future market competition in the hATTR market and insightful review of the SWOT analysis of hATTR.
• Organize sales and marketing efforts by identifying the best opportunities for hATTR in the US, EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan.
• Identification of strong upcoming players in the market will help in devising strategies that will help in getting ahead of competitors.
• Organize sales and marketing efforts by identifying the best opportunities for the hATTR market.
• To understand the future market competition in the hATTR.