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Why Autoimmune Diseases Are Taking Center Stage: Rising Prevalence, Breakthroughs, and Market Opportunities

Why Autoimmune Diseases Are Taking Center Stage: Rising Prevalence, Breakthroughs, and Market Opportunities

Dec 11, 2024PAO-12-24-CL-2

The increasing prevalence of autoimmune diseases presents challenges and opportunities for the biopharmaceutical industry. Conditions like rheumatoid arthritis, lupus, and inflammatory bowel disease (IBD) are becoming more common, with factors like genetic predisposition, environmental triggers, and lifestyle changes contributing to this rise. The growing demand for effective treatments has driven significant advancements in biologic therapies, especially bispecific antibodies and other novel modalities. This article explores the dynamics driving the autoimmune disease market, recent breakthroughs in treatments, and how companies like Fab Biopharma are at the forefront of this promising sector.  

Rising Prevalence of Autoimmune Diseases

The rising prevalence of autoimmune diseases globally has become a prominent public health concern. Studies indicate marked increases in conditions like rheumatoid arthritis, lupus, multiple sclerosis, and type 1 diabetes, with distinct patterns emerging across various demographics. Both age and gender play substantial roles in these trends. Autoimmune diseases such as type 1 diabetes and lupus have shown increased incidence among adolescents and young adults (ages 15-39), whereas diseases like rheumatoid arthritis are more prevalent in older adults. Gender disparities are also notable; women, for instance, have higher rates of systemic lupus erythematosus (SLE) and Sjogren's syndrome, potentially due to hormonal influences and genetic predispositions.1,2  

Environmental and genetic factors further shape susceptibility to autoimmune disease. Ethnicity and geographic location play crucial roles, with specific populations displaying unique vulnerability profiles. For example, individuals of African descent exhibit higher rates of idiopathic inflammatory myopathies, while environmental contaminants, such as mercury exposure in Mediterranean regions, are associated with elevated autoimmune disease risks.3 Additionally, Sjögren's syndrome shows a higher incidence and earlier onset in Asian and Southeast Asian populations compared with Caucasians, reflecting the influence of both genetic and environmental factors. Similarly, a recent study in Elbasan, Albania, underscores that rheumatoid arthritis primarily impacts aging populations, showing variations in prevalence across different demographic strata.4

Decoding the Drivers of Autoimmune Diseases

The global surge in autoimmune diseases has been linked to a complex interplay of environmental, lifestyle, and genetic factors that impact immune function. One prominent environmental contributor is exposure to certain chemicals and pollutants. For instance, a study on multiple sclerosis (MS) found that exposure to air pollutants and industrial chemicals may lead to immune dysregulation, contributing to the global rise in autoimmune cases.5 Additionally, infectious agents are associated with triggering autoimmune responses in genetically susceptible individuals. The presence of specific viral and bacterial pathogens — such as Epstein-Barr virus and Helicobacter pylori — can trigger autoimmune responses in genetically predisposed individuals by altering immune pathways and fostering inflammation.6  

Another critical contributor to autoimmune disease development is the Western diet, high in processed foods and low in fiber. Research suggests that dietary factors contribute to gut dysbiosis — a disruption in the gut microbiome — that can influence immune responses. For example, dietary changes may reduce beneficial microbial diversity, impairing gut barrier function and potentially triggering autoimmunity.7 Furthermore, obesity is an established risk factor, as excess adipose tissue produces pro-inflammatory cytokines, which may exacerbate immune responses and increase susceptibility to autoimmune diseases like rheumatoid arthritis and lupus.8  

Certain medications can also prompt autoimmune responses. Immunosuppressive therapies, while necessary for managing some conditions, have been associated with secondary autoimmune disorders. For example, patients treated with alemtuzumab for multiple sclerosis have demonstrated immune dysregulation, illustrating the potential side effects of these treatments.9  

Genetic predispositions further amplify autoimmune risk when combined with environmental and lifestyle factors. Studies on genetic markers have shown that individuals with specific HLA genotypes are more likely to develop autoimmune conditions when exposed to certain triggers, such as infections or environmental pollutants.10  This intricate interplay of genetic and external factors is now recognized as a foundational element in understanding the global rise in autoimmune diseases.  

Targeted Therapies and the Future of Autoimmune Care

The journey of autoimmune disease treatments has advanced significantly, moving from broad immunosuppressive strategies to highly specialized biological therapies. Each stage of this evolution reflects a deeper understanding of immune mechanisms, as well as the drive toward more effective and safer treatments. This development pathway spans decades, from the initial use of broad-spectrum immunosuppressants to the latest precision therapies like CAR-T cell treatments.  

In the 1950s, corticosteroids emerged as the first major treatment for autoimmune diseases, offering rapid anti-inflammatory effects by suppressing multiple immune pathways. While effective in managing symptoms, these drugs also carry substantial risks, including increased vulnerability to infections and side effects, such as weight gain and bone density loss.11 During the 1960s and 1980s, antimetabolites and cytotoxic drugs, such as methotrexate, were introduced. Initially designed for cancer treatment, methotrexate became a staple therapy for autoimmune conditions like rheumatoid arthritis and psoriasis. However, these drugs were not without challenges; their broad action often led to liver toxicity and bone marrow suppression, limiting their long-term use.12  

By the 1980s and 1990s, selective immunosuppressants like cyclosporine and tacrolimus became available, allowing for more targeted suppression of immune cells, specifically T cells, and proved valuable for autoimmune diseases and organ transplant rejection. Despite improved targeting, these drugs had side effects, such as renal toxicity and high blood pressure, which limited their suitability for long-term management in some patients.  

The late 1990s marked a transformative period with the introduction of biologic therapies, which brought a new level of precision to immune modulation. Tumor necrosis factor (TNF) inhibitors like infliximab and adalimumab were among the first biologics, significantly improving outcomes for patients with conditions such as rheumatoid arthritis and Crohn’s disease by directly targeting pro-inflammatory cytokines.13 Biologics later expanded to include interleukin (IL) inhibitors, such as IL-6 and IL-17 blockers, which proved somewhat effective in managing diseases like ankylosing spondylitis and lupus. B cell–depleting agents such as rituximab also became essential in managing autoimmune diseases driven by autoantibodies, including multiple sclerosis and rheumatoid arthritis. The B cell–modulating antibody drug Benlysta was the first biologic approved for treatment of lupus. These biologics provided more precise immune modulation, though they required regular injections and came with a high cost, which impacted patient adherence and accessibility.14  

In the 2010s, advancements in molecular and cellular therapies broadened treatment options. Small molecule Janus kinase (JAK) inhibitors, such as tofacitinib, offered oral alternatives that interfered with cytokine signaling pathways and proved effective in diseases like rheumatoid arthritis and ulcerative colitis.14  Concurrently, immune checkpoint inhibitors — initially developed for cancer — were investigated for autoimmune applications due to their ability to regulate immune checkpoint proteins like PD-1. However, checkpoint inhibitors risk triggering new autoimmune symptoms, making them a complex addition to the autoimmune therapeutic landscape.15  

Entering the 2020s, precision therapies began to show promise. CAR-T cell therapy, while still experimental in autoimmune diseases, has the potential to selectively target autoreactive cells, as seen in recent lupus studies. This approach could represent a one-time, curative option, although it still poses challenges related to cost and risk management, including severe inflammatory responses like cytokine-release syndrome.16  Furthermore, miniproteins and nanoparticle-based drug delivery systems are emerging as novel approaches, offering potential advantages over traditional biologics. These smaller agents allow for precise targeting with fewer immune rejection issues and enhanced penetration into tissues, though further studies are necessary to validate their long-term safety and efficacy.17  

Currently, biologics — particularly TNF and IL inhibitors — remain predominant in treating chronic autoimmune diseases, with JAK inhibitors providing a convenient oral alternative. For severe or refractory cases, B cell–depleting therapies continue to be a critical option. The modern focus has shifted toward targeted immunotherapy, with ongoing research in precision approaches like CAR-T therapy and nanomedicine holding promise for improved efficacy and reduced side effects.  

Breakthroughs in Treatment and the Rise of Bispecific Antibodies

Bispecific antibody (BsAb) therapies are rapidly advancing, capturing attention across various medical fields, especially in autoimmune diseases. Unlike traditional monoclonal antibodies (mAbs), which typically target a single antigen, BsAbs are engineered to bind two distinct targets at once, allowing them to interact with multiple elements of the immune system simultaneously. This dual-target capability offers a unique advantage, especially in complex conditions like autoimmune diseases, where multiple pathways drive inflammation and disease progression.  

Initially, BsAb development faced challenges in achieving stable, manufacturable, and safe designs. However, recent strides in antibody engineering have led to innovative formats, including single-chain variable fragments (scFvs) and dual-variable domain antibodies (DVD-Igs). IgG-like BsAbs, which retain the Fc region for longer half-life and stability, have also emerged as promising formats.18  These structural innovations allow BsAbs to act with greater therapeutic precision while effectively targeting two distinct molecules.  

Currently, monoclonal antibodies dominate the frontline treatment landscape for autoimmune diseases. These therapies work by inhibiting a single cytokine or immune cell marker to suppress inflammation. For instance, anti-TNF-α therapies like infliximab and adalimumab are staples in treating rheumatoid arthritis and Crohn's disease, while secukinumab, which targets IL-17A, is commonly used for psoriasis. Yet, for many patients, single-target approaches can fall short, especially when multiple inflammatory pathways contribute to disease persistence. BsAbs have the potential to bridge this gap by simultaneously inhibiting two disease-relevant targets, enhancing efficacy and potentially yielding more durable responses.19

One of the primary advantages of BsAbs in autoimmune diseases is their ability to extend therapeutic impact beyond what single-target therapies can achieve. For example, targeting both TNF-α and IL-17A simultaneously could improve outcomes in diseases like psoriasis, where these cytokines play essential roles in inflammation. By addressing two inflammatory mediators, BsAbs could provide more comprehensive control over disease progression, especially in patients who do not respond well to single-target therapies.20  

Moreover, BsAbs hold potential to mitigate immune escape — a phenomenon where disease pathways adapt in response to treatment, allowing the disease to persist. Traditional mAbs often inhibit a single pathway, leaving others to potentially compensate. In contrast, BsAbs could mitigate this risk by blocking multiple pathways, making immune escape more challenging for the disease to achieve. For instance, a BsAb that binds to both IL-6 and its receptor IL-6R could offer enhanced modulation of this inflammatory pathway in rheumatoid arthritis compared to mAbs that target only one component.21  

Beyond immune modulation, BsAbs provide the additional benefit of selective immune cell targeting. In some autoimmune conditions, specific cells contribute to disease progression. BsAbs can be designed to selectively target these pathogenic cells while sparing healthy cells, minimizing unwanted side effects. For instance, a BsAb targeting CD3 on T cells and a specific autoimmune antigen could guide T cells precisely toward harmful cells without broadly suppressing the immune system, a strategy that could prove revolutionary in autoimmune therapies.22  

Interestingly, as blockbuster mAbs approach patent expiration, interest in combining BsAbs with these established therapies is growing. This strategy has two main advantages: it enhances the therapeutic impact of both agents and extends the life cycle of the existing mAb. Combining BsAbs with a well-known mAb like adalimumab, for example, could open new avenues for disease management, providing additional or complementary mechanisms of action. Such combinations not only maximize the therapeutic potential but also offer pharmaceutical companies a way to prolong the commercial viability of their mAb investments.18  

Market Opportunities and Investment Trends

The autoimmune therapies market and the BsAb therapies market are experiencing substantial growth. While the autoimmune therapies market benefits from increasing awareness and diagnoses of autoimmune conditions, the BsAb market is driven by its unique multi-target potential, originally demonstrated in oncology and now expanding strategically into autoimmune diseases. Below is an exploration of each market, as well as a discussion on the shift within BsAb therapies from a predominant focus on oncology to growing applications in autoimmune diseases.  

Autoimmune Therapies Market

The market for autoimmune disease therapies is vast and dynamic, encompassing a broad array of biologic and non-biologic drugs aimed at treating conditions such as rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease (IBD), and lupus. Fueled by rising diagnosis rates and the efficacy of targeted biologics, the market was valued at around $109 billion in 2021 and is projected to exceed $153 billion by 2028, growing at a compound annual growth rate (CAGR) of approximately 4.5%.23  

Biologic drugs, particularly monoclonal antibodies (mAbs), dominate this space due to their targeted approach to modulating immune responses. Key examples include anti-TNF agents, such as adalimumab (Humira) and infliximab (Remicade), which have set the standard for treating autoimmune diseases. Meanwhile, small molecule drugs, especially JAK inhibitors like tofacitinib (Xeljanz), are gaining attention as alternatives to biologics for patients with mAb resistance or intolerance. Recently, BsAbs have emerged as a novel biologic option, though they currently occupy a smaller segment in the market. BsAbs are expected to grow in influence as they gain regulatory approvals and demonstrate therapeutic efficacy in autoimmune settings.18  

Several trends are shaping this market. First, there has been a notable increase in approvals for biologics that target specific cytokines and receptors, allowing for more precise treatment options (Song, 2024). Additionally, as patents on popular biologics such as Humira expire, biosimilars are anticipated to increase access to biologics by reducing costs, particularly in developing regions. The market is also witnessing a shift toward personalized medicine, where treatments are increasingly guided by individual biomarkers, ensuring more effective outcomes for patients with unique immune profiles.19

Combination therapies are also gaining traction as researchers recognize the complexity of immune pathways in autoimmune diseases. Combining biologics with small molecules or BsAbs offers enhanced efficacy by targeting multiple immune pathways and reducing the potential for resistance.21 However, the high cost of biologics remains a barrier to their widespread adoption, and potential side effects, such as increased risk of infection due to immunosuppression, continue to be a challenge for patient adherence.  

Key players in the autoimmune market include AbbVie, with Humira; Johnson & Johnson’s Remicade; Amgen’s Enbrel; Roche’s Actemra; and Pfizer’s Xeljanz. These companies dominate the market due to their extensive biologics portfolios and substantial R&D investments.  

BsAb Therapies Market and Strategic Shift from Oncology to Autoimmune Applications

Initially, the development of BsAbs focused almost exclusively on oncology, where they have demonstrated considerable promise. Oncology-focused BsAbs like blinatumomab (Blincyto) for acute lymphoblastic leukemia (ALL) have paved the way for the broader therapeutic potential of BsAbs. Blincyto’s ability to simultaneously bind to CD19 on cancer cells and CD3 on T cells provided proof-of-concept for BsAbs’ dual-targeting power. While oncology still dominates the BsAb market, a strategic shift toward autoimmune applications is underway, driven by the demand for multi-target approaches in treating complex autoimmune diseases.  

The global BsAb market was valued at approximately $3 billion in 2021, with projections to expand at a CAGR of over 30%, reaching an estimated $13 billion by 2028.23 This rapid growth is not only due to ongoing developments in oncology but also the recognition of BsAbs’ potential in addressing autoimmune diseases, where simultaneous modulation of multiple immune pathways can be particularly advantageous.  

Key Autoimmune Deals: Investment Momentum and Strategic Acquisitions

The autoimmune therapies market has seen a surge of high-value deals, highlighting investor confidence in the potential of new treatments, particularly bispecific antibodies. Over the past six months, several notable transactions have been completed, underscoring the growing focus on autoimmune solutions within both the biotech and pharmaceutical sectors.  

For instance, in May 2024, Johnson & Johnson (J&J) acquired Proteologix, a preclinical-stage biotech developing bispecific antibodies targeting IL-13 and TSLP for atopic dermatitis. This acquisition, valued at a total of $1 billion with $850 million upfront, reflects significant interest in cytokine-targeted therapies. Just weeks later, J&J made another high-profile acquisition, purchasing Yellow Jersey (also known as Numab) for $1.25 billion upfront. Yellow Jersey's lead program is a bispecific antibody targeting IL-4R and IL-31 for autoimmune applications, reinforcing the trend toward dual-target therapies in dermatology and beyond.  

Vertex's acquisition of Alpine Immune Sciences in April 2024 further exemplifies this investment trend. Vertex paid $4.9 billion upfront for Alpine's TACI fusion protein, which targets BAFF and APRIL, key factors in autoimmune conditions. Initially developed for IgA nephropathy, the technology holds potential for broader autoimmune indications, aiming to compete with established therapies like Humira.  

In addition to acquisitions, significant funding rounds reflect ongoing support for innovative autoimmune solutions. Alyx Therapeutics raised $100 million in February 2024, supported by Medicxi, to advance small molecules and biologics targeting dermatitis. Similarly, July saw LTZ Therapeutics secure major funding from Lapam for preclinical work on myeloid-engaging bispecific antibodies, with CD79 as a primary target. More recently, Navigator Therapeutics and Candid Biotherapeutics raised substantial capital, targeting cytokine modulation and T cell engagement for various autoimmune indications.  

These deals collectively illustrate a heightened level of investment and acquisition activity in autoimmune therapies, especially for bispecific antibodies that promise enhanced efficacy through multi-target mechanisms. For companies like Fab Biopharma, this investment momentum is promising, as it validates the strategic shift toward complex therapies that address unmet needs in chronic autoimmune conditions.

Strategic Shift: Why Move from Oncology to Autoimmune Diseases?

The expansion of BsAbs into autoimmune diseases is driven by several factors. Autoimmune diseases are often complex and involve multiple overlapping immune pathways, creating an unmet need for therapies that can modulate multiple targets simultaneously. Unlike cancer, where BsAbs primarily engage immune cells to directly target tumor antigens, in autoimmune diseases, BsAbs can be designed to balance immune responses by inhibiting two or more pro-inflammatory pathways, effectively reducing inflammation without overly suppressing the immune system. For example, BsAbs targeting both TNF-α and IL-17A are currently under investigation for psoriasis, aiming to provide comprehensive inflammatory control for patients who may not fully respond to single-target therapies.20  

Additionally, the regulatory success and clinical efficacy of oncology BsAbs have validated the technology, encouraging pharmaceutical companies to invest in autoimmune-focused BsAbs. There is growing interest in developing BsAbs that can simultaneously block pro-inflammatory cytokines (such as IL-6 and IL-23) or engage immune checkpoints to prevent autoimmunity while preserving immune function.19 Furthermore, many autoimmune conditions lack effective treatment options or have high rates of relapse, which makes them ideal candidates for dual-target approaches.  

Another factor contributing to the shift toward autoimmune diseases is the expiration of patents on blockbuster biologics like Humira. As companies face competition from biosimilars in the autoimmune space, there is a strong incentive to develop innovative biologics, such as BsAbs, which can serve as next-generation therapeutics. By creating BsAbs that complement or enhance the action of existing biologics, companies can differentiate their offerings and potentially extend the commercial life span of their autoimmune drug portfolios.24

Key Trends and Drivers in the BsAb Market

BsAbs’ unique dual-target capabilities have spurred interest in developing therapies that can modulate two disease-relevant pathways simultaneously, addressing unmet needs in autoimmune and chronic inflammatory conditions. Pharmaceutical companies are increasingly forming strategic partnerships and investing in biotech firms specializing in BsAb technology, fueling a competitive pipeline of BsAbs for autoimmune and other indications.25 Regulatory agencies like the U.S. FDA and EMA also support this shift by facilitating expedited approval processes for BsAbs, particularly those addressing autoimmune diseases with high unmet needs. This regulatory adaptability has accelerated R&D and allowed more companies to invest in autoimmune-focused BsAb development.26  

Moreover, many BsAbs are now being developed as part of combination therapy strategies, particularly with established mAbs like adalimumab and rituximab. By pairing BsAbs with well-known therapies, pharmaceutical companies are creating a complementary mechanism of action that could extend the effectiveness of existing treatments. This approach not only has the potential to provide superior outcomes for patients but also strategically benefits pharmaceutical companies by enhancing the commercial viability of blockbuster biologics nearing patent expiry.24  

Challenges and Opportunities Ahead

The shift from oncology to autoimmune applications presents unique challenges, particularly as dual-target therapies introduce new considerations for manufacturing complexity and safety. BsAbs are structurally more intricate than traditional mAbs, requiring sophisticated biomanufacturing processes and quality control measures to ensure stability and efficacy. Additionally, the immune modulation required for autoimmune diseases is inherently different from that in oncology; here, precision and balance are crucial to minimize immune-related side effects while effectively controlling inflammation.  

Despite these challenges, the strategic move into autoimmune diseases is anticipated to accelerate the growth of the BsAb market, especially as more BsAbs enter clinical trials and receive regulatory approval. By addressing unmet needs in autoimmune diseases, BsAbs hold the potential to transform treatment options, providing new hope for patients with complex conditions that are resistant to traditional therapies.

Fab Biopharma’s Unique Position

Fab Biopharma is strategically positioned to meet the rising demand for innovative autoimmune therapies, especially as the therapeutic landscape shifts toward more complex, multi-target treatments like bispecific antibodies. The company’s proprietary platform emphasizes bispecific soluble receptors, which represent a novel approach within the broader bispecifics field. Unlike conventional bispecific antibodies, which can sometimes lead to increased immunogenicity and off-target side effects due to their immune-activating properties, Fab Biopharma’s bispecific soluble receptors are designed to modulate immune pathways with greater precision. This approach enhances target specificity and holds promise for a safer, more tolerable patient experience, addressing common concerns in autoimmune treatments where long-term safety is critical.  

By focusing on bispecific soluble receptors, Fab Biopharma taps into the flexibility of binding multiple targets simultaneously while maintaining a favorable safety profile. This platform could give Fab Biopharma a competitive advantage in the autoimmune market, where the need for effective, low-toxicity therapies continues to grow. As autoimmune diseases often involve complex, multifactorial immune responses, the ability to simultaneously address multiple pathways with a reduced risk of adverse effects could position Fab Biopharma as a leader in the field.

Vision for the Future

Fab Biopharma’s vision extends beyond developing innovative treatments; the company is committed to making these therapies accessible and affordable to a broad patient population. Aware of the financial burden chronic autoimmune diseases place on patients and healthcare systems, Fab Biopharma is focused on creating scalable solutions that ensure long-term affordability without compromising quality. This commitment to scalability is evident in the company’s product pipeline, which prioritizes production processes that can accommodate larger-scale manufacturing without excessive cost.  

By aligning its product development with goals of accessibility and sustainability, Fab Biopharma aims to set a new standard in the autoimmune therapies market. The company’s focus on affordability and long-term solutions not only enhances its competitive edge but also aligns with its mission to deliver sustainable healthcare solutions for chronic autoimmune conditions. Through these efforts, Fab Biopharma envisions a future where patients have access to advanced, life-changing treatments that address the complexities of autoimmune disease management and the practical realities of healthcare accessibility.

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