Felzartamab is a novel, highly targeted biological therapy used to treat immune-driven diseases involving the overproduction of harmful antibodies. It is a humanized monoclonal antibody engineered to precisely interact with specific markers on immune cells. This targeted mechanism offers a potential path for controlling conditions where the body mistakenly attacks its own tissues, providing an alternative to broader immunosuppressive treatments.
Defining Felzartamab and Its Mechanism of Action
Felzartamab is an investigational, fully human immunoglobulin G1 (IgG1) monoclonal antibody designed to selectively target and deplete specific immune cells. Its action is directed against the CD38 glycoprotein, a molecule found at high levels on the surface of mature plasma cells and plasmablasts. These cells are the primary “antibody factories” of the immune system, responsible for producing the autoantibodies that drive autoimmune diseases. By focusing on CD38, felzartamab eliminates the specific cells generating pathogenic antibodies.
The antibody works through several interconnected immune processes to destroy the targeted cells. The primary mechanism is Antibody-Dependent Cellular Cytotoxicity (ADCC), where felzartamab binding tags the plasma cell for destruction by natural killer (NK) cells. The NK cells recognize the antibody-coated target cell and release cytotoxic granules, inducing programmed cell death.
Another pathway is Antibody-Dependent Cellular Phagocytosis (ADCP), where immune cells like macrophages recognize and engulf the antibody-labeled plasma cells for removal. Both ADCC and ADCP lead to the selective depletion of CD38-expressing cells, including long-lived plasma cells often resistant to conventional therapies. This selective depletion reduces the overall pool of cells producing disease-causing autoantibodies, lowering their concentration in the body.
Primary Therapeutic Applications
Felzartamab is primarily focused on immune-mediated diseases where pathogenic autoantibodies cause organ damage. A major area of investigation is Primary Membranous Nephropathy (PMN), a rare autoimmune kidney disease where autoantibodies attack the kidney’s filtering units, leading to protein leakage and kidney failure.
Up to 80% of PMN cases involve autoantibodies directed against the phospholipase A2 receptor (PLA2R). Felzartamab targets the CD38-expressing plasma cells that produce these anti-PLA2R antibodies. Clinical trials show that felzartamab treatment leads to a rapid reduction in circulating pathogenic autoantibodies, preceding improvement in kidney function markers.
The drug is also being studied for Immunoglobulin A Nephropathy (IgAN), the most common form of primary inflammatory kidney disease worldwide. IgAN is characterized by the deposition of abnormal IgA antibodies in the kidney. Early data suggests felzartamab selectively reduces these disease-driving IgA antibody levels, while allowing other antibody types (IgG and IgM) to recover, helping preserve general immune function.
A third application is the treatment of late Antibody-Mediated Rejection (AMR) in kidney transplant recipients. AMR is a leading cause of transplanted kidney loss, driven by donor-specific antibodies produced by plasma cells. Targeting these cells, felzartamab has demonstrated the ability to promote the resolution of the rejection process, offering a novel strategy for a condition lacking effective, approved treatments.
Administration Protocols and Safety Profile
Felzartamab is administered as an intravenous infusion over a defined treatment course. A common regimen uses nine infusions over approximately six months, starting with weekly doses for the first month, followed by less frequent administration, such as every four weeks, to maintain the therapeutic effect.
The infusion is prepared by diluting the drug, often at a dosage of 16 mg/kg, in a solution like 0.9% sodium chloride. Because infusion-related reactions (IRRs) are a recognized side effect, patients often receive pre-medications, such as antihistamines or corticosteroids, beforehand. IRRs typically manifest as mild to moderate symptoms like fever, chills, or difficulty breathing, and are most common during the first administration.
The safety profile of felzartamab is acceptable, with most treatment-related adverse events being mild or moderate. Common adverse events reported in clinical trials include hypogammaglobulinemia, peripheral edema, and nausea. Hypogammaglobulinemia, a reduction in the body’s overall antibody levels, is an expected consequence of depleting antibody-producing plasma cells.
Since reduced antibody levels increase the risk of infection, careful monitoring by the healthcare team is required. Regular monitoring of immunoglobulin levels and kidney function markers is an important part of the treatment protocol to manage the drug’s effects and track disease activity.
Current Regulatory Status and Ongoing Research
Felzartamab is currently an investigational therapeutic candidate and has not yet received final approval from regulatory bodies, such as the U.S. Food and Drug Administration (FDA). However, the FDA granted it Breakthrough Therapy Designation (BTD) for both primary membranous nephropathy (PMN) and late antibody-mediated rejection (AMR). The BTD expedites the development and review of treatments for serious conditions where preliminary evidence suggests substantial improvement over existing therapies.
The drug also received Orphan Drug Designation (ODD) for PMN and AMR, providing incentives to develop treatments for rare diseases. This regulatory support reflects the significant unmet need in these patient populations, as there are currently no FDA-approved therapies specifically for PMN. This status has paved the way for multiple large-scale Phase 3 clinical trials.
Three global Phase 3 studies were initiated in 2025 to test the drug’s efficacy and safety in its primary target indications: the PROMINENT trial for PMN, the PREVAIL trial for IgA nephropathy, and the TRANSCEND trial for late AMR in kidney transplant recipients. Ongoing research is exploring a potential subcutaneous formulation, which would allow for easier administration outside of a hospital setting. Approval filings for the AMR indication are anticipated in the coming years, with PMN expected to follow.