Cold Agglutinin Disease - Market Insight, Epidemiology, and Market Forecast - 2034

Key Highlights:

• Cold agglutinin disease is a rare autoimmune disorder characterized by the premature destruction of red blood cells (hemolysis). 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 symptoms typically develop in individuals between the ages of 40 and 80 and are more common in elder individuals. Symptoms may include hemolytic anemia, profound fatigue, and shortness of breath, acrocyanosis, jaundice, and dark urine.
• The Cold Agglutinin Disease treatment depends on the severity of the clinical symptoms. 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 Cold Agglutinin Disease treatment.
• In the 7MM, the Cold Agglutinin Disease prevalence cases were approximately 13,000 in 2023.
• ENJAYMO, a complement C1s inhibitor monoclonal antibody, is the first FDA-approved drug for treating Cold Agglutinin Disease. This approval has impacted the Cold Agglutinin Disease treatment market landscape significantly, especially in patients with severe anemia.
• Other promising treatments under development for Cold Agglutinin Disease include iptacopan (Novartis), pegcetacoplan (Apellis and SOBI), SAR445088 (Sanofi), and INCB050465 (Incyte).The total Cold Agglutinin Disease drugs market of the US was ~USD 95 million in 2023.
• In 2023, the Cold Agglutinin Disease gender-specific cases were ~40% of males and ~60% cases of females, in US.
• In 2023, approximately 90% of Cold Agglutinin Disease cases in the US were classified as type-specific primary cases, while the remaining 10% were categorized as secondary Cold Agglutinin Disease.

Cold Agglutinin Disease Drugs Market: Report Summary

The Cold Agglutinin Disease Drugs Market report offers extensive knowledge regarding the epidemiology segments and predictions, presenting a deep understanding of the potential future growth in diagnosis rates, disease progression, and treatment guidelines. It provides comprehensive insights into these aspects, enabling a thorough assessment of the subject matter. Additionally, an all-inclusive account of the current management techniques and emerging therapies and the elaborative profiles of late-stage (Phase III and Phase II) and prominent therapies that would impact the current Cold Agglutinin Disease treatment market landscape and result in an overall market shift has been provided in the report.

The Cold Agglutinin Disease Drugs Market report also encompasses a comprehensive analysis of the Cold Agglutinin Disease therapeutics market, providing an in-depth examination of its historical and projected market size (2020 - 2034). It also includes the Cold Agglutinin Disease market share of therapies, detailed assumptions, and the underlying rationale for our methodology. The Cold Agglutinin Disease therapeutics market report also includes drug outreach coverage in the 7MM region.

The Cold Agglutinin Disease Drugs Market Report includes qualitative insights that provide an edge while developing business strategies, by understanding trends, through SWOT analysis and expert insights/KOL views, including experts from various hospitals and prominent universities, patient journey, and treatment preferences that help shape and drive the 7MM Cold Agglutinin Disease therapeutics market.

Cold Agglutinin Disease Recent Developments

• On October 4, 2024, Sanofi struck a deal to sell Enjaymo, its treatment for cold agglutinin disease, to Recordati for a potential $1 billion. Under the agreement, the Italian pharmaceutical company will pay Sanofi $825 million upfront for global rights to the biologic, with the possibility of an additional $250 million in milestone payments. Enjaymo, a humanized monoclonal antibody, treats the rare autoimmune disorder by reducing the risk of hemolysis in patients.

Cold Agglutinin Disease Drugs Market

• Various key Cold Agglutinin Disease Companies are leading the Cold Agglutinin Disease treatment market landscape, such as Novartis, Incyte Corporation, Sanofi and others. The details of the country-wise and therapy-wise Cold Agglutinin Disease market size have been provided below.
• In 2023, the total Cold Agglutinin Disease market size in the 7MM was ~USD 190 million.
• The United States had the largest Cold Agglutinin Disease market size in the 7MM in 2023, followed by Japan.
• ENJAYMO is expected to secure the largest Cold Agglutinin Disease market share in the US by 2034.
• In 2023, the CAD market's largest Cold Agglutinin Disease market share within the EU4 and the UK was held by Germany, amounting to around USD 18 million.
• Germany accounted for the highest total Cold Agglutinin Disease market size in EU4 and the UK, i.e., ~USD 18 million in 2023.

Cold Agglutinin Disease Drugs Market Chapters

The section dedicated to drugs in the Cold Agglutinin Disease drugs market report provides an in-depth evaluation of late-stage pipeline drugs (Phase III, Phase II and Phase I) related to Cold Agglutinin Disease. The Cold Agglutinin Disease drugs market chapters section provides valuable information on various aspects related to Cold Agglutinin Disease clinical trials, such as the pharmacological mechanisms of the drugs involved, designations, approval status, patent information, and a comprehensive analysis of the pros and cons associated with each drug. Furthermore, it presents the most recent newsCold Agglutinin Disease updates and press releases on drugs targeting Cold Agglutinin Disease.

Cold Agglutinin Disease Marketed Therapies

• ENJAYMO (sutimlimab): Sanofi/Bioverativ

ENJAYMO (sutimlimab) is a humanized monoclonal IgG4 antibody directed against human complement factor C1s, a serine protease responsible for the enzymatic propagation of the classical complement pathway (CP), which is a part of the innate immune system. C1s is a part of the C1 complex, a multimeric protein assembly containing the pattern recognition receptor C1q and the C1s-activating serine protease, C1r. By binding to C1s, sutimlimab specifically inhibits the classical pathway, preventing the enzymatic action of the C1 complex on its substrates (C4 and C2), thereby blocking the formation of the pivotal enzyme, C3-convertase. Sutimlimab preserves the functions of the alternative and lectin complement pathways to mediate the humoral surveillance of pathogens. By selectively inhibiting the classical pathway upstream at C1s, sutimlimab did not alter C1q levels or inhibit the lectin and alternative complement pathways.

Cold Agglutinin Disease Emerging Therapies

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). Upon administration, iptacopan binds to FB and prevents the formation of the alternative pathway (AP) C3-convertase (C3bBb). This limits the cleavage of C3 to the active fragment C3b and may prevent C3b-mediated extravascular hemolysis in certain complement-driven disorders such as PNH and CAD.

Iptacopan is one of the most advanced assets in the Novartis nephrology pipeline and has the potential to become the first targeted therapy to delay the progression to dialysis in C3G. Discovered at the Novartis institute for biomedical research, iptacopan is currently in development for several CDRDs where significant unmet needs exist. To investigate the medication in individuals with primary CAD, Novartis Pharmaceuticals is presently doing a Phase II (NCT05086744) basket trial.

INCB050465 (parsaclisib): Incyte Corporation

Parsaclisib, a potent and selective inhibitor of the delta isoform of phosphoinositide-3 kinase (PI3K), demonstrates promising antineoplastic activity with reduced hepatotoxicity compared to first-generation inhibitors. By targeting PI3K-delta, primarily expressed in hematopoietic cells, it inhibits the PI3K/AKT pathway, decreasing proliferation and inducing cell death in PI3K-delta-overexpressing tumor cells. Parsaclisib's selective inhibition aims to spare normal cells' PI3K signaling. It directly blocks tumor cell proliferation and indirectly suppresses tumor growth by inhibiting regulatory T-cells, reducing immunosuppression. Currently, the drug is in Phase II (NCT03538041) clinical stage in patients with autoimmune hemolytic anemia. The trial is also ongoing in the EU clinical trials register (2017-003652-22) for autoimmune hemolytic anemia (AIHA) and includes patients with cold AIHA.

Cold Agglutinin Disease Market Outlook

The 'watch and wait' approach is appropriate in patients with compensated hemolysis or mild anemia, absent or tolerable cold-induced circulatory symptoms, and no unacceptable fatigue. Bendamustine plus rituximab is the preferred choice in moderately to severely affected patients. Rituximab monotherapy is used to maintain its role in frail patients and those with milder diseases. Sutimlimab, if available and affordable, should be preferred even in the first line in severely anemic patients who require a quick response, like in acute exacerbations that do not resolve spontaneously and in patients in whom chemo-immunotherapy is contraindicated.

Many new molecules with novel mechanisms, like cyclic peptide, Monoclonal antibody, Complement C3 inhibitor, Phosphatidylinositol 3 kinase delta inhibitors, among others, are being developed for the Cold Agglutinin Disease treatment by key Cold Agglutinin Disease Companies like Iptacopan (Novartis), and Parsaclisib (Incyte Corporation), among others.

In conclusion, despite the lack of appropriate treatment in the current Cold Agglutinin Disease treatment market landscape, many potential therapies with novel mechanisms are expected to enter the Cold Agglutinin Disease drugs market, resolving a dire unmet need and leading to significant improvement in the treatment outcome of CCold Agglutinin Disease patients. Hence, with the upcoming availability of new treatment options and increasing healthcare spending across the 7MM, the treatment scenario is expected to experience significant growth during the forecast period (2024-2034).

Cold Agglutinin Disease Overview

Cold Agglutinin Disease (CAD) is a rare autoimmune disorder characterized by premature destruction of red blood cells (hemolysis). Autoimmune diseases occur when one's immune system attacks healthy tissue; more specifically, CAD is a subtype of autoimmune hemolytic anemia. Autoimmune hemolytic anemia (AIHAs) are clinic-pathological entities characterized by the production of autoantibodies directed against surface antigens on red blood cells (RBCs). AIHAs are generally classified as warm, cold, or mixed type, depending on the optimum temperature at which the autoantibodies bind surface antigens. In this type of disorder, red blood cells are "tagged" by antibodies and are then destroyed by other types of immune cells. The disease is termed "cold" because the antibodies are active and cause hemolysis at cold temperatures, usually 3-4°C (37-39°F), which is not necessarily the case in other types of autoimmune hemolytic anemia.

Cold Agglutinin Disease Diagnosis

The diagnosis of hemolytic anemia may be suspected based on a thorough clinical evaluation, a detailed patient history, identification of characteristic symptoms, and a variety of tests such as blood tests that measure values of hemoglobin and the percentage of the total blood volume occupied by red blood cells (hematocrit). Blood tests May also show an elevated value of immature red blood cells (reticulocytes), which occurs when the body is forced to produce extra red blood cells to make up for those destroyed prematurely. Some individuals with hemolytic anemia have elevated bilirubin values in the blood (hyperbilirubinemia).

Hemolytic anemia also leads to increased lactate dehydrogenase values (LDH) in the blood, as it is released when red blood cells are destroyed. Haptoglobin is a hemoglobin scavenger that gets consumed when hemoglobin is released in the blood due to hemolysis; haptoglobin values are, therefore, low in hemolytic anemia. When hemolytic anemia is suspected to be autoimmune, specialized tests such as a Coombs test may be performed. This test is used to detect antibodies bound to red blood cells or other biological mediators, like complement (component 3, C3), which accompanies the binding of the immunoglobulin to their targets. A sample of blood is taken and then exposed to the Coombs reagent. A positive test is indicated when the red blood cells clump in the presence of the reagent.

Cold Agglutinin Disease Treatment

Cold Agglutinin Disease treatment involves the management of Cold Agglutinin Disease with lifestyle changes and medications, depending on the severity of symptoms, and in certain emergency cases, blood transfusions might be required. Another factor that decides treatment allocation is whether the patient has primary Cold Agglutinin Disease (CAD happens on its own) or secondary CAD (CAD caused due to another illness). Effective treatments are directed against the pathogenic B-cell clone or the classic complement pathway, and the choice of therapy should be made individually. Additional therapeutic approaches are in the pipeline, for example, BTK inhibition and further development of complement-directed therapies; therefore, patients with CAD requiring treatment should be considered for prospective trials.

Cold Agglutinin Disease Epidemiology

The Cold Agglutinin Disease epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented by Total Cold Agglutinin Disease prevalent cases, total Cold Agglutinin Disease diagnosed cases, Cold Agglutinin Disease gender-specific cases, Cold Agglutinin Disease type-specific cases, total Cold Agglutinin Disease treated cases in the United States, EU4 countries (Germany, France, Italy, Spain) and the United Kingdom, and Japan from 2020 to 2034.

• In 2023, the Cold Agglutinin Disease prevalence cases were ~5,500 in the US.
• In 2023, approximately 90% of Cold Agglutinin Disease cases in the US were classified as type-specific primary cases, while the remaining 10% were categorized as secondary CAD.
• Among EU4 and the UK, the highest number of Cold Agglutinin Disease prevalence cases were in Germany.
• The Cold Agglutinin Disease gender-specific cases were ~1,800 and ~2,660 cases of males and females in 2023, respectively, in the US.

KOL Views

To stay abreast of the latest trends in the Cold Agglutinin Disease treatment market, we conduct primary research by seeking the opinions of Key Opinion Leaders (KOLs) and Subject Matter Experts (SMEs) who work in the relevant field. This helps us fill any gaps in data and validate our secondary research. We have reached out to industry experts to gather insights on various aspects of Cold Agglutinin Disease, including the evolving Cold Agglutinin Disease treatment market landscape, patients' reliance on conventional therapies, their acceptance of therapy switching, drug uptake, and challenges related to accessibility. The experts we contacted included medical/scientific writers, professors, and researchers from prestigious universities in the US, Europe, the UK, and Japan.

Our team of analysts at Delveinsight connected with more than 15 KOLs across the 7MM. We contacted institutions such as the KOL, etc., among others. By obtaining the opinions of these experts, we gained a better understanding of the current and emerging treatment patterns in the Cold Agglutinin Disease treatment market, which will assist our clients in analyzing the overall epidemiology and market scenario.

Qualitative Analysis

We perform Qualitative and Cold Agglutinin Disease Therapeutics 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 safety, efficacy, frequency of administration, designation, 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 trials for CAD, important primary endpoints are evaluation includes assessing hemoglobin levels, C3 levels, total bilirubin levels, and Chronic Illness Therapy (FACIT)-Fatigue Scale scores.

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 route of administration, order of entry and designation, probability of success, and the addressable patient pool for each therapy. According to these parameters, a final weightage score is decided, based on which the emerging therapies are ranked.

Cold Agglutinin Disease Treatment Market Access and Reimbursement

Because newly authorized drugs are often expensive, some patients escape receiving proper treatment or use off-label, less expensive prescriptions. Reimbursement plays a critical role in how innovative treatments can enter the market. The cost of the medicine, compared to the benefit it provides to patients who are being treated, sometimes determines whether or not it will be reimbursed. Regulatory status, target population size, the setting of treatment, unmet needs, the number of incremental benefit claims, and prices can all affect market access and reimbursement possibilities.

The Cold Agglutinin Disease treatment 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.

Cold Agglutinin Disease Treatment Market Report Insights

• Patient-based Cold Agglutinin Disease Market Forecasting
• Therapeutic Approaches
• Cold Agglutinin Disease Market Size
• Cold Agglutinin Disease Market Trends
• Existing Cold Agglutinin Disease Therapeutics Market Opportunity

Cold Agglutinin Disease Treatment Market Report Key Strengths

• 11 Years- Cold Agglutinin Disease Market Forecast
• The 7MM Coverage
• Cold Agglutinin Disease Epidemiology Segmentation
• Key Cross Competition

Cold Agglutinin Disease Treatment Market Report Assessment

• Current Cold Agglutinin Disease Treatment Market Practices
• Reimbursements
• Cold Agglutinin Disease Theraeputics Market Attractiveness
• Qualitative Analysis (SWOT, Conjoint Analysis, Unmet needs)

Key Questions:

• Would there be any changes observed in the current Cold Agglutinin Disease treatment market approach?
• Will there be any improvements in Cold Agglutinin Disease management recommendations?
• Would research and development advances pave the way for future tests and Cold Agglutinin Disease therapies?
• Would the diagnostic testing space experience a significant impact and lead to a positive shift in the Cold Agglutinin Disease treatment market landscape?
• What kind of uptake will the new therapies witness in coming years in Cold Agglutinin Disease patients?