Alpha-1 Antitrypsin Deficiency Market Insight, Epidemiology and Market Forecast - 2034

Key Highlights

• The market size of AATD in the 7MM was around USD 830 million in 2023 and is expected to increase with a significant CAGR during the forecast period.
• Among the 7MM, the United States accounted for the largest market size of AATD, i.e., approximately 84% of the overall market in 2023.
• The total prevalent cases of AATD in the 7MM were ~224,750 in 2023. Prevalence of AATD in Japan is significantly lower than in Europe and the United States
• The current treatment landscape lacks curative therapies. Augmentation therapy, also called replacement therapy, is approved for treating alpha-1-related lung disease. There are four augmentation therapy products available in the US, Grifols’ PROLASTIN-C, Takeda’s ARALAST, CSL Behring’s ZEMAIRA, and Kamada/Takeda’s GLASSIA. RESPREEZA (ZEMAIRA in the US), PROLASTIN, PROLASTINA, PROLASPLAN, PLITALFA, and ALFALASTIN are the augmentation therapies available in selected European countries for AATD. In Japan, PROLASTIN-C is marketed as LYNSPAD.
• PROLASTIN manufactured by Grifols is the market leader among augmentation therapies in AATD based on 2023 sales.
• Key challenges remain in areas such as low diagnosis rate, delay in timely diagnosis, disease awareness, accessibility to genetic testing, availability of disease-modifying treatments, effective management, lack of therapies for liver disease and the discomfort associated with current drug administration methods. New therapies are emerging to address these gaps.
• Key players such as Kamada Pharmaceuticals (Inhaled AAT), Arrowhead Pharmaceuticals and Takeda (Fazirsiran), Mereo BioPharma/AstraZeneca (Alvelestat), Sanofi/Inhibrx Biosciences (SAR447537/INBRX-101), Wave Life Sciences (WVE-006), Beam Therapeutics (BEAM-302), Grifols (Alpha-1 15%), Krystal Biotech (KB408), and others are evaluating their assets in different stages of clinical development and will significantly impact the AATD market during the forecast period (2024-2034).
• While there are no licensed pharmacological treatments available for patients with AATD-associated liver disease, fazirsiran appears as a potentially transformative approach offering a transformative alternative to liver transplants, currently the only effective option.
• Inhaled therapies and self-administered treatments are poised to revolutionize the patient experience, such as Kamada Pharmaceuticals' Inhaled AAT, if approved, would be the first AATD treatment that avoids weekly intravenous infusions.
• Alpha-1 15%, developed by Grifols, represents a first in-human subcutaneous approach, which if approved would drastically ease the treatment burden of AATD.
• As emerging treatments like gene therapies (KB408, BEAM-302, and others) and RNA-editing therapy (WAVE-006) move closer to potential approvals, the market could soon offer more durable, minimally invasive options that significantly improve patient quality of life and set new standards in AATD care.
• Few of the assets, such as Novo Nordisk’s belcesiran and Vertex’s VX-864 have failed in their respective clinical trials due to adverse events or inability to achieve the primary endpoint.
• Ongoing research and an increase in disease understanding have led to the identification of therapies with effective and convenient routes of administration, including subcutaneous, inhalation, and oral, with the potential to improve patient’s quality of life, setting the stage for market expansion and reshaping patient expectations and treatment experiences.

This report delivers an in-depth understanding of AATD, historical and forecasted epidemiology as well as the AATD market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

The AATD market report provides current treatment practices, emerging drugs, AATD market share of individual therapies, and current and forecasted AATD market size from 2020 to 2034, segmented by seven major markets. The report also covers current AATD 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

Study Period: 2020-2034

AATD Disease Understanding and Treatment Algorithm

AATD Overview

According to the National Organization for Rare Disorders (NORD), alpha-1 antitrypsin deficiency (AATD) is a hereditary disorder characterized by low levels of a protein called alpha-1 antitrypsin (AAT) found in the blood. This deficiency may predispose an individual to several illnesses and most commonly manifests as chronic obstructive pulmonary disease (COPD) (including bronchiectasis) and liver disease (especially cirrhosis and hepatoma) or, more rarely, as a skin condition called panniculitis.

The etiology and pathogenesis of AATD involve a complex interaction between genetic and environmental factors, resulting in immune-mediated reactions affecting the lungs, liver, and skin. The SERPINA1 gene mutations lead to the inadequate production and improper functioning of the AAT protein. This deficiency can result in serious lung and liver complications. A deficiency of A1AT allows substances that break down proteins (so-called proteolytic enzymes) to attack various body tissues. The attack results in destructive lung changes (emphysema) and may affect the liver and skin.

AATD Diagnosis

AATD may first be suspected in people with liver disease symptoms at any age or who have symptoms of lung disease (such as emphysema), especially when there is no obvious cause, or it is diagnosed at a younger age. So, AATD testing is recommended for all adults with emphysema, COPD, or asthma whenever airflow obstruction is present or incompletely reversible after optimized treatment with a bronchodilator. Other rarer forms of AATD might be present, so unexplained bronchiectasis, granulomatosis with polyangiitis, necrotizing panniculitis, and liver disease of unknown etiology should prompt further AATD testing. Once the diagnosis is made, familial testing is advocated since AATD is a heritable disease.

AATD Treatment

The primary purpose of treatment is to improve the manifestation of liver and lung disease developed due to AATD. Behavioral, lifestyle modification, medical, and surgical treatment are recommended for individuals with AATD.

Current treatment for AATD includes both medicinal and surgical therapies. Both of these categories provide symptomatic relief to the subjects based on the level and severity of their conditions. Commonly used therapy for AATD is similar to COPD and emphysema treatment: abstinence from smoking, long-acting bronchodilators, antibiotics, inhalations of corticosteroids, and long-acting beta-agonists are recommended. However, applying such solutions does not increase the functional AAT level in serum. Further, lung transplantation may be an appropriate option for individuals with end-stage lung disease, and liver transplantation is the definitive treatment for severe AATD-associated liver disease to restore AAT levels in the body. Augmentation therapy, also called replacement therapy, is approved for treating alpha-1-related lung disease.

Therefore, no specific therapy is available for the liver disease associated with AATD. However, animal studies have shown promise for several drugs that can increase the liver’s ability to break down unsecreted A1AT (e.g., rapamycin and carbamazepine) and have prompted research studies in AATD individuals.

AATD Epidemiology

The AATD epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by the Total Prevalent Cases of AATD, Total Diagnosed Prevalent Cases of AATD, Genotype-specific Prevalent Cases of AATD, and Comorbidity-associated Cases of AATD in the 7MM covering the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan from 2020 to 2034.

• Among the 7MM, the US accounted for approximately 59%, EU4 and the UK for 40%, and Japan for 1% of the total prevalent cases of AATD in 2020.
• The total diagnosed prevalent cases of AATD in the United States is estimated to be ~10,700 in 2023. The cases are expected to increase by 2034.
• Among EU4 and the UK, in 2023, the UK accounted for the highest AATD cases, followed by Germany.
• As per estimates, in 2020, in the US, comorbidity associated with lung diseases was most common, occurring in around 77% of the total AATD cases, followed by other diseases occurring in around 15% of the cases, while 8% of the cases had liver diseases.

AATD Drug Chapters

Marketed Drugs

PROLASTIN-C LIQUID/LYNSPAD: Grifols

PROLASTIN-C LIQUID is an A1-PI indicated for chronic augmentation and maintenance therapy in adults with clinical evidence of emphysema due to severe hereditary deficiency of A1-PI. PROLASTIN increases the antigenic and functional levels of serum and antigenic lung epithelial lining fluid levels of A1-PI. PROLASTIN-C LIQUID is the first ready-to-infuse liquid formulation of an A-1 antitrypsin deficiency replacement therapy manufactured in the US. It requires less preparation time than the lyophilized product and less volume for infusion compared to others.

In October 2009, PROLASTIN-C was approved by the FDA for the treatment of individuals with AATD and evidence of emphysema. Later in September 2017, PROLASTIN-C liquid was approved by the US FDA for chronic augmentation and maintenance therapy in adults with clinical evidence of emphysema due to severe AATD. In November 2022, Grifols announced that its AlphaID At Home Genetic Health Risk Service, the first-ever free direct-to-consumer program in the US to screen for genetic risk of AATD, has been cleared by the US FDA.

GLASSIA: Kamada Pharmaceuticals/Takeda

GLASSIA is an intravenous AAT product that is indicated for chronic augmentation and maintenance therapy in individuals with clinically evident emphysema due to severe hereditary deficiency of A1-PI. GLASSIA increases antigenic and functional (anti-neutrophil elastase capacity, ANEC) serum levels and antigenic lung epithelial lining fluid levels of alpha1 -PI.

In July 2010, the US FDA approved GLASSIA for the treatment of chronic augmentation and maintenance therapy in individuals with clinically evident emphysema due to severe hereditary deficiency of A1-PI. Later in June 2016, the US FDA approved an expanded label for GLASSIA to treat emphysema due to severe AATD that can be self-infused at home after appropriate training. In April 2021, Kamada amended the GLASSIA license agreement with Takeda. Under the amendment, Kamada transferred the GLASSIA US BLA to Takeda.

Emerging Drugs

Inhaled Alpha 1-Antitrypsin (AAT): Kamada Pharmaceuticals

Inhaled AAT, an investigational medicine researched for AATD patients, aims to replace the deficient AAT protein in the lung. It acts as an immunomodulator (serine peptidase inhibitor) that prevents inflammation and tissue degradation by regulating the imbalance of proteases and antiproteases in the lungs.

Inhaled AAT received positive scientific advice from the EMA that reconfirmed the overall design of the ongoing study and acknowledged the statistically and clinically meaningful improvement in lung functioning. In March 2016, Kamada submitted an MAA to EMA for the inhaled AAT to treat AATD. However, later, in 2017, it was withdrawn due to insufficient data. Currently, the company is conducting a Phase III clinical trial to evaluate the safety and efficacy of Kamada AAT for Inhalation in the EU and has completed Phase II and II/III trials in the US and EU, respectively.

As per the news released in Q2 2024 report, Kamada Pharmaceuticals has filed an IND amendment with the FDA consisting of a revised Statistical Analysis Plan (SAP) and study protocol, which, if approved, may allow for the acceleration of the program of its ongoing pivotal Phase III InnovAATe clinical trial for the inhaled AAT.

Fazirsiran (ARO-AAT/TAK-999): Arrowhead Pharmaceuticals and Takeda

Fazirsiran is an investigational RNA interference therapy designed to reduce the production of mutant alpha-1 antitrypsin protein (Z-AAT) as the first potential treatment for liver disease associated with AATD. In October 2020, Takeda Pharmaceuticals and Arrowhead Pharmaceuticals announced a collaboration and licensing agreement to develop fazirsiran to treat AATD. The drug has received BTD, FTD and ODD from the US FDA to treat AAT-associated liver disease.

Currently, Arrowhead Pharma is advancing fazirsiran in two Phase III studies, REDWOOD (NCT05677971) in patients with AATD-associated liver disease with METAVIR Stage F2-F4 Fibrosis and another trial (NCT06165341) for patients with AATD-associated liver disease with METAVIR Stage F1 Fibrosis.

Drug Class Insight

Neutrophil elastase enzyme inhibitor

Neutrophil elastase inhibitors specifically target and block the activity of neutrophil elastase. This action helps prevent the breakdown of elastin and other connective tissues in the lungs, slowing the progression of emphysema and preserving lung function. By regulating neutrophil elastase levels, these inhibitors help restore the normal balance between proteases and antiproteases that are disrupted in the treatment of AATD. Mereo Biopharma’s Alvelestat, a neutrophil elastase inhibitor is in development for AATD-associated lung disease.

AATD Market Outlook

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that can lead to lung and liver disease. Early diagnosis and appropriate medical care are important for managing the condition and improving the quality of life for individuals with AATD. The current treatment landscape lacks curative and disease-modifying therapies. Augmentation therapy, also called replacement therapy, is approved for treating alpha-1-related lung disease. Several off-label drugs are used for symptomatic relief and managing lung-related complications like COPD or emphysema; bronchodilators, corticosteroids, and antibiotics are commonly used. In the severe stage of the disease, a surgical option like lung volume reduction surgery and bullectomy is recommended, and patients with very advanced emphysema may require lung transplant surgery, which involves removing a damaged lung and replacing it with a healthy lung; however, it involves many risks, including infection and rejection. AATD is commonly associated with liver disease; however, no therapy has yet been approved to address liver-associated disease. Treatment is designed to maintain normal nutrition and to provide the liver and the body with essential nutrients. IV replacement therapy, majorly used to manage lung diseases, utilizes AAT protein from healthy human donors’ blood plasma to augment the alpha-1 levels in the blood and lungs diagnosed with emphysema.

The views on augmentation therapies differ in the respective countries, with some therapies being available in only a particular country, whereas some countries are devoid of any augmentation therapy. Currently, four augmentation therapy products are available in the US, approved by the US FDA; Grifols’ PROLASTIN-C, Takeda’s ARALAST, CSL Behring’s ZEMAIRA, and Kamada/Takeda’s GLASSIA. In Europe, currently, RESPREEZA (ZEMAIRA in the US), PROLASTIN, PROLASTINA, PROLASPLAN, PLITALFA, and ALFALASTIN are the augmentation therapies available in selected European countries for AATD. Since the prevalence of AATD in Japan is estimated to be very low as compared to the US and Europe, resulting in fewer patients to date, only one augmentation therapy, i.e., LYNSPAD (PROLASTIC C liquid), has been approved in Japan.

Pharma companies are actively working toward the development of therapeutic options for AATD associated with lung and liver disease including Arrowhead Pharma/Takeda, Kamada, Mereo BioPharma/AstraZeneca Sanofi/Inhibrx Biosciences Wave Life Sciences, and others.

• Among the 7MM, the US accounted for the largest market size of AATD. i.e., USD ~700 million in 2023.
• Among EU4 and the UK, Germany accounted for the highest market size in 2023, while the UK occupied the lowest.
• The pipeline for AATD consists an innovative therapies including an immunomodulator (serine peptidase inhibitor), neutrophil elastase enzyme inhibitor, RNA editing therapy, gene therapies, and others.
• In 2034, among all the emerging therapies, the highest revenue is expected to be generated by PROLASTIN/PROLASTIN-C/LYNSPAD in the 7MM.

Key Updates

• In October 2024, Wave Life Sciences announced that it is expecting to share multidose data from the RestorAATion-2 trial in 2025.
• In September 2024, Krystal Biotech amended the protocol for its KB408 Phase I SERPENTINE-1 study to include mandatory bronchoscopies in this cohort to measure alpha-1 antitrypsin expression.
• In July 2024, Beam Therapeutics entered into a settlement agreement with a research institution pursuant to which, in exchange for a release of claims in its favor, the company agreed, among other things, to pay the research institution an upfront payment of USD 15 million and to make additional payments contingent upon the development and commercialization of BEAM-302.
• In February 2024, Grifols announced that it had introduced 4 and 5 g vials of PROLASTIN used for long-term AAT augmentation therapy in patients with severe AATD who show evidence of progressive lung disease.
• In January 2024, the US FDA approved the supplement Biologics License Application (sBLA) for Alpha-1-Proteinase Inhibitor ZEMAIRA.

To be continued in the report….

AATD Drugs Uptake

This section focuses on the uptake rate of potential drugs expected to be launched in the market during 2020-2034. The landscape of AATD treatment has experienced a profound transformation with the uptake of novel drugs. These innovative therapies are redefining standards of care. Furthermore, the increased uptake of these transformative drugs is a testament to the unwavering dedication of physicians, oncology professionals, and the entire healthcare community in their tireless pursuit of advancing cancer care. This momentous shift in treatment paradigms is a testament to the power of research, collaboration, and human resilience.

Given the promising efficacy results of siRNA-based approaches in early phase II clinical trials in liver-associated AATD, fazirsiran is expected to have a fast uptake.

AATD Pipeline Development Activities

The report provides insights into different therapeutic candidates in Phase III, Phase II, PhaseI/II, Phase I, and preclinical developement. 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 AATD 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, Professor and Vice Chair Department of Critical Care Medicine and Director, PhD, and others. Their opinion helps to understand and validate current and emerging therapies and treatment patterns or AATD market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

The analysts connected with 20+ KOLs to gather insights; however, interviews were conducted with 10+ KOLs in the 7MM. Centers such as the RWTH Aachen University Hospital, University of Valencia, Vall d'Hebron University Hospital, Drexel University, Saint Louis University, University of Birmingham, Juntendo University, Kyoto University, etc., were contacted. Their opinion helps understand and validate AATD epidemiology and market trends.

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.

The analyst analyzes multiple emerging therapies based on relevant attributes such as safety, efficacy, frequency of administration, route of administration, and order of entry.

In efficacy, the trial’s primary and secondary outcome measures are evaluated.

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.

Market Access and Reimbursement

The PROLASTIN DIRECT Program

PROLASTIN-C LIQUID (Grifols)

• It is a comprehensive program that uses experts exclusively dedicated to Alpha1 to provide personalized support for patients receiving PROLASTIN-C LIQUID. The PROLASTIN DIRECT program is managed by EVERSANA, the only specialty pharmacy that fills prescriptions for PROLASTIN-C LIQUID. The program provides the patient with a team dedicated to alpha-1 care that will assist with securing insurance coverage, coordinating infusions, and managing one's health with their physician's guidance. The program's patient service coordinator is the primary point of contact the patient can rely on for everything related to the treatment.
• It assists Alpha1 expert nurses and pharmacists 24 h a day, 7 days a week. One can take comfort in knowing that the PROLASTIN DIRECT program handles every detail of the patient's infusion, from shipping medicine, scheduling infusion, and administering infusion everything is handled.
• The PROLASTIN DIRECT program works with health insurance to determine if the patient has received an infusion at home, at work, infusion center, or even while traveling. Additionally, it also covers disease management through AlphaNet.
• Moreover, an individual's insurance is reviewed every year to ensure effective coverage.

GLASSIA

Takeda Patient Support Copay Assistance Program

Takeda Patient Support assists the patient in the following ways:

• Enroll in the Takeda Patient Support Copay Assistance Program if the patient qualifies*
• Work with specialty pharmacy (or site of care) to help the patient receive GLASSIA
• Arrange for a trained nursing professional to teach the patient or a caregiver how to infuse the treatment at home, if requested by the healthcare provider
• Navigate the health insurance process
• Direct the patient to community support resources and education
• Provide the patient with tips and timely information throughout GLASSIA treatment

*To be eligible, the patient must be enrolled in Takeda Patient Support and have commercial insurance.
The Takeda Patient Support Copay Assistance Program may help the patient save on the prescribed Takeda treatment.†

The program can cover up to 100% of the patient’s out-of-pocket copay costs if the patient is eligible. To be eligible for this program, the patient must:

• Be prescribed a Takeda treatment for a condition that the FDA approves to treat
• Have commercial insurance.
• Be enrolled in Takeda Patient Support.

Scope of the Report

• The report covers a descriptive overview of AATD, explaining its causes, signs and symptoms, pathogenesis, and currently available therapies.
• Comprehensive insight has been provided into AATD epidemiology and treatment.
• Additionally, an all-inclusive account of both the current and emerging therapies for AATD is provided, along with the assessment of new therapies, which will have an impact on the current treatment landscape.
• A detailed review of the AATD market; historical and forecasted 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 AATD market.

AATD Report Insights

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

AATD Report Key Strengths

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

AATD Report Assessment

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

FAQs

• What was the AATD market share (%) distribution in 2020 and what it would look like in 2034?
• What would be the AATD total market size as well as market size by therapies across the 7MM during the study period (2020-2034)?
• Which country will have the largest AATD market size during the study period (2020-2034)?
• What are the disease risks, burdens, and unmet needs of AATD?
• What is the historical AATD 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 AATD?
• How many emerging therapies are in the mid-stage and late stage of development for the treatment of AATD?
• What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, and licensing activities related to AATD therapies?
• What are the recent novel therapies, targets, mechanisms of action, and technologies developed to overcome the limitations of existing therapies?
• What are the clinical studies going on for AATD and their status?
• What are the key designations that have been granted for the emerging therapies for AATD?

Reasons to buy

• The report will help in developing business strategies by understanding trends shaping and driving AATD.
• To understand the future market competition in the AATD market and Insightful review of the SWOT analysis of AATD.
• Organize sales and marketing efforts by identifying the best opportunities for AATD 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 AATD market.
• To understand the future market competition in the AATD market.