Cold Agglutinin Disease Market Insight, Epidemiology And Market Forecast - 2032

Key Highlights

• Cold agglutinin disease (CAD) is a rare autoimmune disorder characterized by the premature destruction of red blood cells (hemolysis); approximately 4,500 patients are found in the United States.
• Cold Agglutinin Disease is four times more common in colder climates, and the incidence rates in these regions spike during the winter months.
• Approximately 90% of Cold Agglutinin Disease patients have immunoglobulin M (IgM)-mediated disease, while IgG and IgA-mediated cases are rarely reported.
• Cold Agglutinin Disease accounts for 15-30% of autoimmune hemolytic anemias (AIHA).
• According to reported literature, 40-50% of patients with Cold Agglutinin Disease are transfusion-dependent, and the median age of onset is around 65-67 years, with the disease having a noticeable female predominance.
• In 2022, the market of Cold Agglutinin Disease was highest in the US among the 7MM, accounting for approximately USD 55 million, which is further expected to increase by 2032.
• Until 2022, the treatment setting of Cold Agglutinin Disease was dominated by corticosteroids, followed by rituximab and its combinations, and other management therapies.
• In February 2022, the US FDA approved ENJAYMO (sutimlimab) to decrease the need for red blood cell transfusion due to hemolysis in adults with Cold Agglutinin Disease. This made it the first and only approved treatment for Cold Agglutinin Disease.
• ENJAYMO is a complement C1s inhibitor and the first FDA-approved therapy for Cold Agglutinin Disease, which physicians have readily adopted for caring for Cold Agglutinin Disease.
• Rituximab monotherapy is often used as the first-line therapy for treating Cold Agglutinin Disease. Although, neither in the United States nor Europe is Rituximab approved for treating Cold Agglutinin Disease.
• Among the emerging therapies, three promising drugs are Sobi/Apellis' ASPAVELI/EMPAVELI (pegcetacoplan), Novartis' iptacopan, and Incyte's parsaclisib, which have the potential to create a significant positive shift in the Cold Agglutinin Disease market size.

This “Cold agglutinin disease (CAD) - Market Insights, Epidemiology and Market Forecast - 2032 report delivers an in-depth understanding of the Cold agglutinin disease, historical and forecasted epidemiology as well as the Cold agglutinin disease market trends in the United States, EU4 (Germany, Spain, Italy, and France) and the United Kingdom, and Japan.

Cold agglutinin disease market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted 7MM Cold agglutinin disease (CAD) market size from 2019 to 2032. The report also covers current Cold agglutinin disease (CAD) treatment practices/algorithms and unmet medical needs to curate the best opportunities and assess the market's underlying potential.

Geography Covered

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

Study Period: 2019-2032

Cold Agglutinin Disease (CAD) Understanding and Treatment AlgorithmCold Agglutinin Disease Overview

Cold Agglutinin Disease (CAD) is a rare autoimmune disorder characterized by prematurely destroying the red blood cells (RBCs) (hemolysis). It is a subtype of autoimmune hemolytic anemia (AIHA). AIHAs are generally classified as warm, cold, or mixed type, depending on the optimum temperature at which the autoantibodies bind with surface antigens. In CAD, the red blood cells are destroyed prematurely, and the production rate of new cells in the bone marrow can no longer compensate for their loss.

Cold Agglutinin Disease Diagnosis

A Cold Agglutinin Disease diagnosis is generally made through physical exams and laboratory tests. Additional tests may be required to identify the underlying cause of the disease in the case of secondary CAD, a form of Cold Agglutinin Disease associated with other illnesses, including infections, cancers, or other autoimmune disorders. Further tests may also be required to differentiate CAD from other diseases that can lead to the premature destruction of red blood cells.

Blood samples taken at a hospital or clinic may be used to diagnose Cold Agglutinin Disease. The blood is analyzed using multiple laboratory tests, including a complete blood count, a blood smear, biochemical tests, the Coombs test, a cold agglutinin titer, or a thermal amplitude test.

Cold Agglutinin Disease TreatmentThe treatment of Cold Agglutinin Disease depends on the severity of the clinical symptoms. Currently, the therapeutic market of CAD is majorly acquired by nonpharmacological (cold avoidance) and pharmacological management, including Rituximab monotherapy and combination therapy, plasmapheresis, and transfusions. The FDA approved ENJAYMO in February 2022 as the first and only treatment indicated to decrease the need for red blood cell transfusion due to hemolysis in adults with CAD. The Japanese Ministry of Health, Labor, and Welfare approved ENJAYMO in June 2022, and in November 2022, the European Commission (EC) granted marketing authorization for ENJAYMO.

The current therapeutic market for Cold Agglutinin Disease is dominated by nonpharmacological (cold avoidance) and pharmacological management. Corticosteroids, alkylating agents, purine nucleoside analogs, and majorly biologics, such as rituximab monotherapy or combination therapy (fludarabine and rituximab, bendamustine and rituximab) and others are the major therapeutic line of treatment for CAD.

The first treatment shown to be effective in Cold agglutinin disease was rituximab monotherapy, 375 mg/m2 once a week for 4 weeks; rituximab is often used as a first-line therapy. If patients do not respond to rituximab, it can be combined with other drugs, such as bendamustine and fludarabine, administered orally has resulted in higher response rates and sustained remissions. Although rituximab alone or in combination is still the most widely used treatment, it is likely to be replaced with emerging therapies expected to launch in the future.

Over the next few years, the US Cold Agglutinin Disease Market is expected to change and experience growth substantially, as it will be dominated by one already approved product, ENJAYMO (sutimlimab). In contrast, we also anticipate the launch of a second product, Pegcetacoplan, in the US market in the coming 2-3 years. We expect the market to expand, especially as safer and more effective therapies enter the market.

Cold Agglutinin Disease Epidemiology

As the market is derived using a patient-based model, the Cold agglutinin disease epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by total prevalent cases of Cold Agglutinin Disease, total diagnosed cases of Cold Agglutinin Disease, gender-specific cases of Cold Agglutinin Disease, type-specific cases of Cold Agglutinin Disease, and total treated cases of Cold Agglutinin Disease in the 7MM covering the United States, EU4 countries (Germany, France, Italy, and Spain), United Kingdom, and Japan from 2019 to 2032. The total diagnosed prevalent cases of Cold Agglutinin Disease in the 7MM comprised approximately 10,300 cases in 2022 and are projected to increase during the forecasted period.

• The total number of diagnosed prevalent cases of Cold Agglutinin Disease in the United States was around 4,300 cases in 2022.
• The United States contributed to the largest prevalent population of Cold Agglutinin Disease, acquiring ~43% of the 7MM in 2022. Whereas EU4 and the UK, and Japan accounted for around 42% and 16% of the total population share, respectively, in 2022.
• Among the EU4 countries, Germany accounted for the largest number of diagnosed Cold Agglutinin Disease cases, followed by France, whereas Spain accounted for the lowest number of cases in 2022.
• According to the publisher's estimates, there were around 4,000 cases of primary and 500 cases of secondary Cold agglutinin disease in the United States in 2022. The prevalence is projected to increase during the forecasted period.
• In 7MM, ~40% of the patient share is attributed to males, whereas only 60% of females have Cold agglutinin disease.

Cold Agglutinin Disease Drug Chapters

The drug chapter segment of the Cold Agglutinin Disease report encloses a detailed analysis of Cold agglutinin disease marketed drugs and late-stage (Phase III and Phase II) pipeline drugs. It also helps understand the Cold Agglutinin Disease 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

ENJAYMO (sutimlimab): Sanofi/Bioverativ

ENJAYMO (sutimlimab), is a monoclonal antibody targeting the classical complement pathway (CP) specific serine protease (C1s), thereby inhibiting CP activity which is associated with a variety of immune disorders involving the presence of autoantibodies. It is the first and only approved therapeutic option approved for hemolytic anemia in adult patients with cold agglutinin disease. It was approved by the Japanese Ministry of Health, Labor, and Welfare in June 2022 and granted marketing authorization by the European Commission in November 2022. ENJAYMO'S approval in Europe was based on data from two Phase III studies, CADENZA and CARDINAL.

Sanofi estimates that the annual cost for ENJAYMO is around USD 280,000 per year before discounts or rebates, in line with other drugs used to treat rare, chronic diseases. KOLs estimate that ENJAYMO could make more than USD 500 million in sales by 2026.

Note: Detailed current therapies assessment will be provided in the full report of Cold agglutinin disease…

Emerging Drugs

ASPAVELI/EMPAVELI (pegcetacoplan): Swedish Orphan Biovitrum/Apellis Pharmaceuticals

ASPAVELI/EMPAVELI (pegcetacoplan) is a PEGlyated pentadecapeptide developed by Apellis Pharmaceuticals in collaboration with Swedish Orphan Biovitrum (Sobi) to treat complement-mediated diseases. It binds to complement component 3 (C3) and its activation fragment C3b, controlling the cleavage of C3 and resulting in the generation of the downstream effectors of complement activation and thus both C3b-mediated extravascular hemolysis and terminal complement-mediated intravascular hemolysis.

The company has recently started a Phase III (NCT05096403) clinical study to test the drug for treating Cold Agglutinin Disease. The anti-C3 cyclic peptide pegcetacoplan appears to be a promising drug in treating Cold Agglutinin Disease and may also have therapeutic potential in treating warm autoimmune hemolytic anemia.

LNP023 (iptacopan): Novartis

Iptacopan is an investigational, first-in-class, orally administered, small-molecule inhibitor of complement factor B (FB) with potential immunomodulatory activity and targeting one of the key drivers of several complement-driven renal diseases (CDRDs). Novartis pharmaceuticals are conducting a Phase II (NCT05086744) basket trial to study the drug in patients with primary Cold agglutinin disease.

Note: Detailed emerging therapies assessment will be provided in the final report.

Drug Class Insights

The existing Cold agglutinin disease treatment is mainly dominated by classes such as anti-inflammatories, antimetabolites, Immunosuppressants, antianemics, and complement inhibitors.

Complement inhibitors are grouped into two categories, soluble regulators and membrane-bound regulators. These regulators naturally protect self-cells and tissues from unwanted complement activation. Now, there are nine complement inhibitors approved by the FDA, including C1 inhibitor BERINERT, CINRYZE, RUCONEST, AND ENJAYMO (sutimlimab), C3 inhibitor EMPAVELI (pegcetacoplan), SYFOVRE (pegcetacoplan injection), and C5 inhibitor SOLIRIS (eculizumab), ULTOMIRIS (ravulizumab) and TAVNEOS (avacopan) for the treatment of various indications. As of now, only the drug ENJAYMO (sutimlimab), which the US FDA approves for the treatment of Cold Agglutinin Disease, is a complement inhibitor.

Moreover, the upcoming treatment landscape is poised to expand further after new classes such as PI3K inhibitors, emerge.

Cold Agglutinin Disease Market Outlook

Cold Agglutinin Disease treatment in the US is entering a new era with changing dynamics. Therapeutic options for Cold agglutinin disease are limited. The treatment landscape was dominated by legacy, generic therapies such as corticosteroids, rituximab, rituximab-fludarabine regimen, bendamustine, azathioprine, erythropoietin, methotrexate, cyclosporine, or vincristine, etc.

The current market has been segmented into different commonly used therapeutic classes based on the prevailing treatment pattern across the 7MM, which presents minor variations in the overall prescription pattern. corticosteroids, rituximab monotherapy, rituximab in combination, ENJAYMO (sutimlimab), and others are the major classes covered in the forecast model.

The expected launch of upcoming therapies and greater integration of early patient screening, medication in secondary care and other clinical settings, research on best methods for implementation, and an upsurge in awareness will eventually facilitate the development of effective treatment options. However, there are a few roadblocks regarding these patients' timely diagnosis and treatment; for instance, during COVID-19. These factors often become a hindrance for both physicians and patients when adopting newer therapies.

Key players such as Sobi/Apellis Pharmaceuticals (ASPAVELI/EMPAVELI), Novartis (Iptacopan; LNP023), and Incyte Corporation (Parscaclisib; INCB050465) are investigating their candidates for the management of Cold Agglutinin Disease in the 7MM.

• The total market size of Cold Agglutinin Disease in the 7MM is approximately USD 85 million in 2022 and is projected to increase during the forecast period (2023-2032).
• The market size in the 7MM will increase at a CAGR of 24% due to increasing awareness of the disease and the launch of the emerging therapy.
• Among EU4 countries, Germany accounts for the maximum market size in 2022, while Spain occupied the bottom of the ladder in 2022.
• In Japan, available medications include corticosteroids, rituximab monotherapy, rituximab in combination, ENJAYMO (sutimlimab), and others (alkylating agents, azathioprine, erythropoietin, danazol, interferon alpha, plasma exchange, intravenous immunoglobulin, methotrexate, cyclosporine, or vincristine, etc.).

Cold Agglutinin Disease Drugs Uptake

This section focuses on the uptake rate of potential drugs expected to be launched in the market during 2019-2032. For example, for pegcetacoplan, we expect the drug uptake to be medium-fast with a probability-adjusted peak share of 14%, years to the peak is expected to be 7 years from the year of launch.

Further detailed analysis of emerging therapies drug uptake in the report.

Cold Agglutinin Disease Pipeline Development Activities

The report provides insights into different therapeutic candidates in Phase III, Phase II, and Phase I stage. 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 Cold agglutinin disease emerging therapies.

KOL Views

To keep up with current market trends, we take KOLs and SME's opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry Experts contacted for insights on the Cold Agglutinin Disease evolving treatment landscape, patient reliance on conventional therapies, patient's therapy switching acceptability, and drug uptake along with challenges related to accessibility, including Medical/scientific writers, Professors, Chief Medical Officer of Coeus Consulting Group, Hematology Specialist and Others.

This analysts connected with 50+ KOLs to gather insights; however, interviews were conducted with 15+ KOLs in the 7MM. Hospitals and universities such as McGill University School of Medicine, Harvard Medical School, Boston Children's Hospital, etc., were contacted. Their opinion helps understand and validate current and emerging therapy treatment patterns or Cold agglutinin disease market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

Qualitative Analysis

The publisher performs 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 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 approved and emerging therapies based on relevant attributes such as the mechanism of action, efficacy, frequency of administration, route of administration, and order of entry. Scoring is given based on these parameters to analyze the effectiveness of therapy.

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

Reimbursement of rare disease therapies can be limited due to lack of supporting policies and funding, challenges of high prices, lack of specific approaches to evaluating rare disease drugs given limited evidence, and payers' concerns about budget impact. The high cost of rare disease drugs usually has a limited impact on the budget due to the small number of eligible patients being prescribed the drug. The US FDA has approved several rare disease therapies in recent years. From a patient perspective, health insurance and payer coverage guidelines surrounding rare disease treatments restrict broad access to these treatments, leaving only a small number of patients who can bypass insurance and pay for products independently.

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

Scope of the Report

• The report covers a segment of key events, an executive summary, descriptive overview of Cold agglutinin disease, explaining its causes, signs and symptoms, pathogenesis, and currently available therapies.
• Comprehensive insight has been provided into the epidemiology segments and forecasts, the future growth potential of diagnosis rate, disease progression, and treatment guidelines.
• Additionally, an all-inclusive account of the current and emerging therapies, along with the elaborative profiles of late-stage and prominent therapies, will impact the current treatment landscape.
• A detailed review of the Cold agglutinin disease 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 preference that help shape and drive the 7MM Cold agglutinin disease market.

Cold Agglutinin Disease Report Insights

• Patient Population
• Therapeutic Approaches
• Cold Agglutinin Disease Pipeline Analysis
• Cold Agglutinin Disease Market Size and Trends
• Existing and Future Market Opportunity

Cold Agglutinin Disease Report Key Strengths

• Ten Years Forecast
• 7MM Coverage
• Cold agglutinin disease Epidemiology Segmentation
• Key Cross Competition
• Attribute analysis
• Drugs Uptake and Key Market Forecast Assumptions

Cold Agglutinin Disease Report Assessment

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

Key Questions Answered

Market insights

• What was the Cold agglutinin disease total market size, the market size by therapies, market share (%) distribution in 2019, and what would it look like in 2032? What are the contributing factors for this growth?
• What kind of uptake complement inhibitors will ENJAYMO (sutimlimab) witness in the coming 10 years?
• How will pegcetacoplan, and iptacopan compete with ENJAYMO?
• Which class is going to be the largest contributor in 2032?
• What are the pricing variations among different geographies for approved and off-label therapies?
• How would the market drivers, barriers, and future opportunities affect the market dynamics and subsequent analysis of the associated trends?

Epidemiology insights

• What are the disease risk, burdens, and unmet needs of Cold agglutinin disease? What will be the growth opportunities across the 7MM with respect to the patient population pertaining to Cold agglutinin disease?
• What is the historical and forecasted Cold agglutinin disease patient pool in the United States, EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan?
• What factors are affecting the increase in the diagnosis of symptomatic cases?

Current treatment scenario, marketed drugs, and emerging therapies

• What are the current options for the treatment of Cold Agglutinin Disease? What are the current treatment guidelines for the treatment of Cold Agglutinin Disease in the US and Europe?
• How many companies are developing therapies for the treatment of Cold agglutinin disease?
• How many emerging therapies are in the mid-stage and late stage of development for the treatment of Cold agglutinin disease?
• What are the recent novel therapies, targets, mechanisms of action, and technologies developed to overcome the limitation of existing therapies?
• What have key designations been granted for the emerging therapies for Cold agglutinin disease?
• What is the cost burden of approved therapies on the patient?
• Patient acceptability in terms of preferred treatment options as per real-world scenarios?
• What are the country-specific accessibility issues of expensive, recently approved therapies? Focus on reimbursement policies.
• What are the 7MM historical and forecasted market of Cold Agglutinin Disease?

Reasons to Buy

• The report will help develop business strategies by understanding the latest trends and changing treatment dynamics driving the Cold agglutinin disease 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 opportunity in varying geographies and the growth potential over the coming years.
• Distribution of historical and current patient share based on real-world prescription data along with reported sales of approved products in the US, EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan.
• Identifying strong upcoming 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 of approved therapies, barriers to accessibility of expensive off-label therapies, and patient assistance programs.
• To understand Key Opinion Leaders' perspectives around the accessibility, acceptability, and compliance-related challenges of existing treatment to overcome barriers in the future.
• Detailed insights on the unmet need of the existing market so that the upcoming players can strengthen their development and launch strategy.