The antibody-mediated rejection market is estimated to be valued at USD 126.5 Mn in 2024 and is expected to reach USD 291.1 Mn by 2031, growing at a compound annual growth rate (CAGR) of 12.64% from 2024 to 2031. The market is mainly driven by increasing solid organ transplant procedures globally along with rising investments in development of novel therapeutics for treatment of antibody-mediated rejection post-transplant.

Market Driver - Increasing Number of Organ Transplants Globally

Growing awareness about organ donation, coupled with state-of-the-art surgical techniques, have enabled doctors to successfully carry out complex transplant procedures on a regular basis now. This has significantly boosted the total number of organ transplants performed worldwide each year. For instance, data from the Organ Procurement and Transplantation Network (OPTN) in the United States shows that the volumes have steadily increased over the past decade, with over 40,000 transplants done in 2021 alone.

However, despite the donor organ coming from a well-matched donor, there is always a risk of rejection by the recipient's immune system. Herein lies the role of medications that suppress the immune system or interfere with its rejection mechanism. With the rising transplantation rates globally, demand for anti-rejection drugs is growing in tandem.

Pharmaceutical companies are investing heavily in developing more effective and targeted immunosuppressants that can help improve transplant outcomes. Some newer agents even aim to induce immunotolerance, allowing transplant patients to eventually get off immunosuppression in the long run. All these factors point towards a continuously expanding patient pool who may potentially require lifelong anti-rejection medications, thus propelling the associated market forward.

Market Driver - Advancements in Therapies Targeting the Immune System's Rejection Mechanisms

Medical science continues advancing at a rapid pace, bringing numerous beneficial changes within the field of transplant immunology. Researchers have decoded intricate details about how the immune system recognizes non-self-tissues and initiates an attack. Pharmaceutical firms are leveraging immunological insights through dedicated R&D efforts focused on developing next-gen prophylactics.

Some examples include biological drugs inhibiting specific co-stimulatory molecules on immune cells or antibodies neutralizing inflammatory cytokines released during allograft rejection. Clinical studies evaluating these biologics show effective suppression of immune activation without broad suppression, translating to improved graft function and patient survival. Another promising arena is gene therapy whereby introduction or silencing of certain genes can help generate antigen-specific non-responsiveness or operational tolerance towards transplanted organs. Such targeted strategies are anticipated to replace conventional non-specific immunosuppressants over the long run.

Additionally, technologies like transplant tolerance induction through mixed chimerism hold promise. Here, bone marrow stem cells from the donor are transfused to establish mutual hematopoietic cell populations between donor and recipient. As outcomes from these novel therapies start yielding positive results in the coming years, they could transform anti-rejection medication use post-transplantation. This further validates strong growth dynamics for the overall market against this backdrop.

Market Challenge - High treatment costs and limited access to novel therapies

One of the major challenges currently faced by the antibody-mediated rejection market is the high costs of treatments and limited access to novel and emerging therapies. Antibody-mediated rejection treatments involve the use of immunosuppressive drugs such as infliximab, rituximab and intravenous immunoglobulin, which are very expensive for patients and healthcare systems to afford. The average annual drug cost for treating antibody-mediated rejection has been estimated to range from $20,000 to over $100,000 per patient. Additionally, many novel therapies that are still in development or have recently been approved are not widely accessible or affordable for all patients yet due to various factors. Partial coverage by insurance plans and health systems makes these newer treatment options out of reach for some patients. The high economic burden of antibody-mediated rejection treatments poses difficulties for broader patient access globally and threatens the sustainability of healthcare budgets. Wider adoption of novel and emerging therapies also depends on demonstrating superior clinical benefits over existing options as well as successful negotiations on drug pricing with payers. These access challenges must be addressed to improve treatment outcomes for more antibody-mediated rejection patients worldwide.

Market Opportunity - Development of Novel Drugs that Target Key Inflammatory Pathways

A major opportunity in the antibody-mediated rejection market lies in the development of novel drugs that target key inflammatory pathways associated with the condition. For instance, Clazakizumab is a monoclonal antibody against IL-6 that has shown promise in reducing acute rejection episodes in clinical trials. IL-6 is a major pro-inflammatory cytokine implicated in antibody-mediated injury to transplanted organs.

Similarly, Imlifidase is an enzyme therapy designed to enzymatically degrade IgGs which play a central role in triggering antibody-mediated rejection. In phase 2 trials, Imlifidase has demonstrated efficacy in desensitizing highly sensitized patients prior to kidney transplants.

As novel mechanisms of action, Clazakizumab and Imlifidase have potential to deliver superior clinical outcomes compared to existing therapies. Their approval in the coming years could help address unmet needs in patient subgroups with high antibody levels.

Furthermore, targeting new inflammatory pathways may yield options for synergistic combination therapies with immunomodulators. This represents a significant opportunity to improve patient prognoses and quality of life.

Antibody-mediated rejection (AMR) is commonly treated through a step-wise approach based on severity and stage of rejection. For mild AMR early after transplantation, prescribers typically start with increased immunosuppression using medications like tacrolimus (Prograf), mycophenolate mofetil (CellCept), and corticosteroids.

If symptoms fail to improve with boosted baseline immunosuppression, prescribers may progress treatment to a first-line therapy of plasmapheresis and intravenous immunoglobulin (IVIg). Plasmapheresis is used to filter antibody-coated donor cells from circulation, while IVIg provides unclear benefits through immunomodulation. Brands prescribed include Fenwal Plasma Collection System for plasmapheresis and Gamunex,Octagam or Privigen for IVIg.

For cases still unresponsive to first-line treatment or those presenting with more severe acute AMR, prescribers often use rituximab (Rituxan) - a monoclonal antibody targeting B cells. This second-line therapy aims to deplete antibody-producing cells. Non-responders or those with chronic, active AMR may progress to third-line options like bortezomib (Velcade), a proteasome inhibitor with mechanistic benefits, or eculizumab (Soliris), a complement inhibitor targeting inflammation pathways.

Other factors influencing prescriber choices include side effect profiles, cost considerations, insurance coverage for branded products, and availability of generics or biosimilars where applicable. Close monitoring of renal function and antibody levels also helps determine treatment success over time.

Antibody-mediated rejection (AMR) has three main stages - subclinical, clinical, and chronic active AMR. For subclinical AMR, the preferred first-line treatment involves the use of intravenous immunoglobulin (IVIG). IVIG works by suppressing antibody production and is generally well-tolerated.

For clinical AMR, the standard first-line treatment combination includes plasma exchange + IVIG + thymoglobulin/rabbit anti-thymocyte globulin (rATG)/basiliximab. Plasma exchange is used to rapidly remove anti-donor antibodies from circulation. IVIG provides additional immunosuppression along with rATG/basiliximab which are potent T-cell depleting agents. This triple therapy aims to simultaneously eliminate antibodies and suppress immune cells.

In cases where first-line therapy fails or for chronic active AMR, second-line treatments such as bortezomib, eculizumab or rituximab are used. Bortezomib is a proteasome inhibitor that suppresses plasma cells producing antibodies. Eculizumab blocks terminal complement system to prevent tissue damage from AMR. Rituximab depletes B-cells, reducing new antibody production.

For recurrent or refractory AMR, aggressive approaches involving combinations of above drugs may be employed. These include rATG/bortezomib or eculizumab/bortezomib to achieve synergistic suppression of both humoral and cellular immunity. Early detection and prompt treatment at each stage of AMR leads to better long-term graft survival outcomes.

Focus on innovative drug development - Companies like Bristol-Myers Squibb and Alexion Pharmaceuticals have invested heavily in R&D to develop novel therapeutic antibodies targeting specific pathways involved in AMR. For example, in 2020, Bristol-Myers Squibb's belimumab (Benlysta) received FDA approval for the treatment of AMR in kidney transplant recipients.

Acquisitions and partnerships - Large players have acquired smaller biotechs working on promising AMR drug candidates to gain access to their pipelines. For instance, in 2015 Alexion acquired Synageva to obtain Synageva's clinical-stage C5 complement inhibitor (ALXN1210), which showed potential in preventing AMR in trials. This strengthened Alexion's portfolio.

Focus on real-world evidence generation - Companies provide support for large longitudinal studies and clinical registries that help generate real-world evidence on treatment patterns and outcomes. For example, data from the National Transplantation Pregnancy Registry established with Bristol-Myers Squibb's support showed belimumab was well-tolerated in transplant recipients, supporting its approval and adoption.

Awareness initiatives for clinicians - Educational programs and marketing efforts help create awareness among nephrologists, transplant surgeons and immunologists about the role of specific targets like C5a in AMR pathogenesis and utility of new drugs. This helped Bristol-Myers Squibb gain first-mover advantage with belimumab post approval.

Insights, By Treatment: Widespread Availability and Clinical Efficacy Drive Plasma Exchange Adoption

In terms of treatment, plasma exchange is expected to account for 35.3% share of the antibody-mediated rejection market in 2024, owning to its widespread availability and proven clinical efficacy. As an apheresis procedure, Plasma Exchange technology is well established in hospitals and transplantation centers globally. The equipment and disposables required for plasma exchange are standardized and produced by several major medical device companies, ensuring reliable access.

Additionally, plasma exchange has a long history of clinical use for treating acute antibody-mediated transplant rejection, with numerous studies demonstrating improved graft survival when used as a first-line treatment option. Its ability to rapidly clear pathogenic antibodies from circulation through selective replacement of plasma constitutes a logical and physiological approach.

The procedure is also generally well-tolerated with a relatively safe side effect profile. Moreover, experience with plasma exchange among clinicians performing renal transplants provides heightened familiarity and comfort prescribing it. The combined factors of broad availability, clinical evidence, supplier network, practicality of use and familiarity amongst medical professionals have made Plasma Exchange the segment leader in antibody removal therapy.

Insights, By Drugs in Development: Promising Efficacy Data Positions Clazakizumab Atop Antibody-mediating Rejection Drugs in Development

In terms of drugs in development, Clazakizumab contributes the highest share of the antibody-mediated rejection market due to emerging efficacy data from clinical trials. Clazakizumab is a monoclonal antibody that inhibits the pro-inflammatory cytokine interleukin-6 (IL-6). Beyond its immunomodulatory effects, preclinical research indicates IL-6 plays a direct role in promoting antibody production. An ongoing Phase 2 clinical study is evaluating Clazakizumab for preventing antibody-mediated rejection in kidney transplant recipients.

Preliminary data presented at a recent scientific conference demonstrated reduced donor-specific antibody levels and subclinical rejection events compared to placebo. If borne out in the full trial results, this could establish Clazakizumab as the first systemic drug shown effective for antibody-mediated rejection prophylaxis in a randomized controlled study.

The promising results to date have generated substantial interest within the transplantation community and piqued investors’ attention for this first-in-class mechanism. Barring any safety concerns in subsequent trials, Clazakizumab seems well positioned to become the leading therapeutic in this segment pending regulatory approvals.

Insights, By Therapeutic Approach: Superior Target Specificity Drives Monoclonal Antibodies in Antibody-mediated Rejection Therapeutic Approaches

In terms of therapeutic approach, monoclonal antibodies contribute the highest share of the market owing to their exquisite target specificity. Unlike conventional immunosuppressive therapies, monoclonal antibodies allow selective blockade of molecules involved in antibody production and response rather than systemic immune suppression.

For example, anti-CD20 antibodies selectively deplete B cells responsible for alloantibody secretion without fully ablating humoral immunity. Complement inhibitors provide a less precise approach by broadly inhibiting multiple complement activation pathways throughout the body.

Monoclonal antibodies’ ability to pinpoint key players in the rejection cascade while sparing off-target immunity renders them particularly well-suited for antibody-mediated transplant issues. Drugs like Belimumab targeting BAFF are being assessed for preventing sensitized patients’ pre-formed donor-specific antibodies from rebounding.

Additionally, many transplantation centers employ low-dose IVIG preparations enriched for anti-CD20 to deplete long-lived plasma cells in refractory cases. The precision these targeted biological therapies afford coupled with improving recombinant antibody manufacturing techniques continue driving interest and segment share for monoclonal antibodies in Antibody-mediated Rejection treatment.

• AMR represents a spectrum of conditions coexisting with T-cell-mediated rejection, often leading to allograft loss and characterized by donor-specific antibodies.
• The US leads the antibody-mediated rejection cases in the 7MM, representing over 60% of total cases.
• Kidney, lung, and liver transplant cases were the top contributors to antibody-mediated rejection cases in the 7MM in 2023.
• France had the highest number of antibody-mediated rejection cases in the EU4.
• Antibody-mediated rejection affects approximately 5-7% of all kidney transplants, with acute AMR being particularly challenging to treat due to the variability in patient response. The lack of standardized treatment guidelines further complicates patient management, with therapies largely based on off-label use from other areas of medicine.

The major players operating in the antibody-mediated rejection market include CSL Behring, Hansa Biopharma AB, Viela Bio, Janssen Biotech, Pfizer, Sanofi, HI-Bio, and Horizon Therapeutics.

• In March 2024, Human Immunology Biosciences (HI-Bio) announced that the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to felzartamab for the treatment of antibody-mediated rejection (AMR) in kidney transplant recipients. This designation is a significant step for the development of felzartamab, a monoclonal antibody that targets CD38+ plasma cells, which play a key role in AMR. The Orphan Drug Designation helps to promote the development of treatments for rare diseases, offering incentives like tax credits and market exclusivity upon approval​.
• In January 2024, Hansa Biopharma AB published positive results from its Imlifidase trials, focusing on acute AMR cases where conventional treatments failed, marking a breakthrough in treatment options for transplant recipients. The trials demonstrated that imlifidase significantly reduced donor-specific antibodies (DSAs) within five days of treatment, marking a significant breakthrough for transplant recipients facing rejection where conventional treatments had failed. This is particularly important for patients with AMR, a leading cause of graft failure, as there are currently no approved therapies for this condition. The promising results from these phase 2 trials showed that imlifidase was more effective and faster at reducing DSAs compared to traditional plasma exchange treatments​.
• In May 2023, CSL Behring advanced Clazakizumab into Phase III clinical trials to investigate its potential in treating chronic active antibody-mediated rejection (AMR) in kidney transplant recipients. This is a critical area of research because AMR is a leading cause of late kidney graft loss, and current treatment options are limited.
• In October 2018, the U.S. Food and Drug Administration (FDA) granted Fast Track Designation to imlifidase, a drug developed by Hansa Biopharma, for investigating its use in transplantation. Specifically, imlifidase is being studied for its potential to enable kidney transplantation in highly sensitized patients by inactivating harmful antibodies that can otherwise cause organ rejection.

• By Treatment
  • Plasma Exchange
  • IVIG
  • Complement Inhibitors
  • Proteasome Inhibitors
• By Drugs in Development
  • Clazakizumab
  • Imlifidase
• By Therapeutic Approach
  • Monoclonal Antibodies
  • Complement Inhibitors
• By Patient Type
  • Pre-sensitized Transplant Recipients
  • Acute AMR Patients