The cold agglutinin disease drugs market is estimated to be valued at USD 134 Mn in 2024 and is expected to reach USD 558 Mn by 2031, growing at a compound annual growth rate (CAGR) of 22.6% from 2024 to 2031.

Factors such as the rising prevalence of cold agglutinin disease, growing awareness about the disease, and increasing research and development activities for novel treatment options are expected to drive the demand for cold agglutinin disease drugs during the forecast period.

Market Driver - FDA Approval of ENJAYMO, the First Drug Specifically Targeting CAD

The approval of ENJAYMO by the US Food and Drug Administration (FDA) has provided a major boost to the cold agglutinin disease drugs market. ENJAYMO, developed by Apellis Pharmaceuticals, is the first drug approved for the treatment of autoimmune hemolytic anemia caused by cold agglutinin disease in adults. This represents a significant breakthrough as cold agglutinin disease was previously an area of high unmet medical need with very limited treatment options.

The approval was based on positive results from the Phase 3 PEGASUS trial which evaluated the safety and efficacy of subcutaneous pegcetacoplan compared to the standard of care, which is usually steroids, in both naïve and relapsed/refractory patients with CAD. Pegcetacoplan was also found to be generally well tolerated with a safety profile consistent with complement inhibition.

The approval of the first ever treatment specifically for CAD has filled an important void and means doctors now have an approved therapeutic option to help patients achieve stable hemoglobin levels and improve their quality of life. It is expected that ENJAYMO's superior efficacy demonstrated in the PEGASUS trial will drive rapid adoption among physicians.

Market Driver - Rising Prevalence of CAD among Aging Populations

CAD occurs more commonly in the elderly, with the average age of patients being around 70 years. As life expectancies increase worldwide, the population of elderly individuals is growing at an unprecedented rate. For example, the proportion of the world's population over 60 years is projected to nearly double from 12% to 22% between 2015 and 2050. The number of Americans aged 65 and older is also escalating rapidly and is estimated to reach over 98 million by 2060.

As the population ages, more people are at risk of developing CAD. The risk of most autoimmune diseases, including CAD, increases with age due to age-associated weakening of regulatory immune mechanisms. Moreover, elderly individuals are also more prone to develop infectious triggers which can induce CAD. With such strong synergies between advancing age and CAD etiology, the sharp rise in global elderly demographics is directly driving up the prevalence of the disease.

Doctors as well as patients are also now more educated on CAD since the approval of the first drug for the condition. All these factors tied to the aging trend are expected to significantly contribute to the growth of the cold agglutinin disease drugs market in the coming years.

Market Challenge - High Cost of Emerging Biologics and Treatments

One of the major challenges for the cold agglutinin disease drugs market is the high cost of emerging biologics and specialized treatments. Cold agglutinin disease is a rare condition with a limited patient pool worldwide. Developing therapies specifically for this rare condition requires extensive research and clinical trials. This development process is highly expensive and the costs are ultimately passed on to patients in the form of high drug prices.

Most patients find it difficult to afford such expensive therapies for long-term management of their condition. This poses significant barriers for market growth as patients may discontinue treatments or not seek medical help due to the prohibitive costs.

Pharmaceutical companies also recover their R&D investments through high drug prices. However, this makes the treatments inaccessible for a large section of patients. Governments and insurance companies struggle to provide coverage and reimbursement for such expensive orphan drugs.

Overall, the high prices of emerging targeted therapies, biologics and other specialized treatment modalities remain a major challenge for wider market adoption and growth of this therapeutic segment.

Market Opportunity - Expansion of Pipeline Therapies such as Iptacopan and Parsaclisib

One of the major opportunities for the cold agglutinin disease drugs market is the expansion of the product pipeline with promising new therapies such as Iptacopan and Parsaclisib. Iptacopan, under development by Apellis Pharmaceuticals, is an oral terminal complement inhibitor that has shown significant therapeutic potential in clinical trials for treating cold agglutinin disease.

In another development, Incyte is evaluating selective PI3Kδ inhibitor Parsaclisib for various hematological conditions including cold agglutinin disease. The successful development and approval of these pipeline therapies can provide patients with more treatment options beyond conventional therapies. It can also increase access by offering oral alternatives to expensive biologics and infusions.

A richer pipeline is likely to fuel future market growth by addressing the significant unmet needs in cold agglutinin disease management. It may also improve treatment outcomes and quality of life for patients suffering from this rare blood condition.

Cold agglutinin disease (CAD) can be classified into three stages based on severity of symptoms:

Mild CAD involves slight discomfort from cold exposure but no organ damage. Treatment focuses on avoiding triggers and maintaining warmth.

Moderate CAD presents with moderate anemia and fatigue. First-line treatment is corticosteroids such as prednisone, which reduces immune system activity and CAD symptoms. Splenectomy may also be considered to remove spleen cells producing cold agglutinins.

Severe CAD results in severe anemia requiring blood transfusions or organ damage like kidney failure. Treatment first aims to control the symptoms with high-dose corticosteroids and immunosuppressants like rituximab or cyclophosphamide. Rituximab, a monoclonal antibody, is increasingly the preferred treatment. By targeting B-cells producing CAD antibodies, it provides rapid and sustained responses with fewer side effects than chemotherapy. For severe cases non-responsive to rituximab, the combination of rituximab and cyclophosphamide gives better efficacy than monotherapy. A splenectomy may further improve the response if the spleen is a major source of agglutinin production. Bone marrow or stem cell transplant is considered for refractory cases. Close monitoring is needed to prevent complications from immunosuppression.

Strategy: Focus on developing innovative treatment options

An example is Alexion Pharmaceuticals, which has developed a first-in-class monoclonal antibody called Ultomiris (ravulizumab) for treating Cold Agglutinin Disease (CAD). Ultomiris was approved by the FDA in 2021 based on positive results from a Phase 3 clinical trial where it showed significantly reduced risk of hemolysis compared to standard of care. This made Ultomiris the first and only FDA-approved treatment for CAD.

Strategy: Pursue acquisitions to expand pipeline

For example, in 2017, Apellis Pharmaceuticals acquired Potentia Pharmaceuticals to gain its C3 inhibitor Pegcetacoplan, which was being evaluated for CAD and paroxysmal nocturnal hemoglobinuria (PNH). In a Phase 2 study, Pegcetacoplan led to a significant reduction in serum lactate dehydrogenase (LDH) levels in CAD patients, indicating reduced hemolysis. This acquisition allowed Apellis to enter the CAD treatment space with a promising mid-stage candidate, complementing its existing assets.

Strategy: Target orphan drug designations and approvals

Given the small patient populations, players seek orphan drug status to maximize commercial potential. For instance, Ultomiris secured orphan drug designation from the FDA and EMA for CAD. This conferred 7 and 10 years of market exclusivity in the US and EU respectively upon approval.

Insights, By Treatment Approach: Rising Prevalence of Cold Agglutinin Disease Drives Growth of Rituximab Monotherapy

In terms of treatment approach, rituximab monotherapy contributes the highest share of the market owning to its effectiveness against Cold Agglutinin Disease. Rituximab is a monoclonal antibody used to treat various hematological malignancies and autoimmune disorders. It works by targeting CD20, a surface marker found on pre-B and mature B lymphocytes.

Rituximab causes B cell lysis and depletion, thereby reducing pathological antibody production. For Cold Agglutinin Disease, Rituximab depletes CD20-positive plasma cells that produce the disease-causing cold agglutinins, thus providing rapid relief from hemolytic anemia symptoms. Its targeted mechanism of action enables complete remission in 70-80% patients.

Moreover, Rituximab monotherapy has a favorable safety profile with minimal adverse effects. These clinical benefits have led to its widespread adoption among physicians treating Cold Agglutinin Disease.

Insights, By Pipeline Drugs: Parsaclisib Drives Growth in the Iptacopan Segment

In terms of pipeline drugs, Iptacopan contributes the highest share of the market due to the promising clinical data of Parsaclisib. Iptacopan is an oral inhibitor of the complement C5a receptor which is under late-stage development by InflaRx for various autoimmune and inflammatory indications. Parsaclisib is a next-generation, highly selective oral inhibitor of PI3Kδ currently in Phase II clinical trials.

In a recent PI3Kδ inhibition study, Parsaclisib demonstrated a sustained reduction in serum immunoglobulins and improvement in hematologic parameters in patients with cold agglutinin disease and anderemic purpura. This encouraging efficacy combined with a favorable safety profile has increased the appeal of Iptacopan as a potential disease-modifying therapy. Positive data from ongoing trials could lead to early approval and market access for Iptacopan, making it the preferred treatment choice over conventional options.

Insights, by Type of Disease: Unmet Needs in Diagnosis and Management Drives Growth of Primary Cold Agglutinin Disease Segment

In terms of by type of disease, primary cold agglutinin disease contributes the highest share of the market owing to significant unmet needs in disease diagnosis and management. Primary cold agglutinin disease refers to cases where no underlying cause can be identified for the production of cold agglutinins.

Current diagnostic evaluation relies on screening tests with low sensitivity, while management focuses on symptomatic relief through transfusions and immunosuppression. This leaves room for improving early detection through better diagnostic markers as well as curative therapies.

Several biotechs are exploring disease-modifying targets like complement system inhibition to potentially achieve remission. As research advances treatment paradigms, the Primary Cold Agglutinin Disease segment is poised for growth to address its substantial unmet needs.

• In 2023, there were approximately 13,000 cases of Cold Agglutinin Disease in the 7MM.
• In the US, 90% of CAD cases are primary, and 10% are secondary.
• ENJAYMO Impact: Approved as the first-ever treatment for CAD, significantly changing the management of severe anemia associated with CAD.

The major players operating in the cold agglutinin disease drugs market include Sanofi, Novartis, Incyte Corporation, Apellis Pharmaceuticals, and Sobi.

• The FDA approved Enjaymo (sutimlimab-jome) in February 2022 as the first treatment specifically targeting the complement system's C1s protein for Cold Agglutinin Disease (CAD), a rare autoimmune hemolytic anemia. This drug inhibits the destruction of red blood cells by blocking C1s, a part of the classical complement pathway, which is a critical driver of hemolysis in CAD.
• Novartis is currently investigating Iptacopan (LNP023) in Phase II clinical trials as a potential treatment for primary Cold Agglutinin Disease (CAD), among other complement-driven diseases. Iptacopan is a first-in-class, oral, selective inhibitor of complement factor B, which is part of the alternative complement pathway. The drug aims to inhibit the underlying processes driving CAD, such as complement-mediated hemolysis.
• Incyte's Parsaclisib is a promising drug currently being evaluated in Phase II trials for treating autoimmune hemolytic anemia (AIHA). Parsaclisib is a highly selective inhibitor of the PI3K delta pathway, which plays a crucial role in the survival and proliferation of B cells involved in autoimmune conditions like AIHA. The drug has shown potential in improving hemoglobin levels in patients with AIHA without excessive toxicity, as presented in clinical trials in 2022​.

• By Treatment Approach
  • Rituximab monotherapy
  • Corticosteroids
  • Biologics like ENJAYMO
• By Pipeline Drugs
  • Iptacopan
  • Parsaclisib
  • Pegcetacoplan
• By Type of Disease
  • Primary Cold Agglutinin Disease
  • Secondary Cold Agglutinin Disease