What Is Felzartamab?

Felzartamab is a therapeutic human monoclonal antibody derived from MorphoSys’ HuCAL antibody library and directed against CD38. Felzartamab is an investigational drug that has not yet been approved by any regulatory authorities. The safety and efficacy of felzartamab are currently evaluated in patients with glomerulonephritis including anti-PLA2R antibody-positive membranous nephropathy (MN) and IgA nephropathy (IgAN), both autoimmune renal diseases. In the future, felzartamab might potentially be evaluated as targeting therapy in additional autoimmune mediated diseases.

In June 2022, MorphoSys and Human Immunology Biosciences, Inc. (HIBio), a South San Francisco-based biotechnology company focused on discovering and developing precision medicines for autoimmune and inflammatory diseases, entered into an equity participation agreement and license agreements under which HIBio obtained exclusive rights to develop and commercialize felzartamab across all indications worldwide, with the exception of Greater China. Prior to this, in November 2017, MorphoSys entered into an exclusive regional licensing agreement with I-Mab Biopharma to develop and commercialize felzartamab in Greater China.

Therapeutic fields and proposed mode of action

Glomerulonephritis (GN) is a group of renal disorders that cause damage to the glomeruli, the filtration units of the kidney, hindering their ability to carry out their essential functions. Membranous nephropathy (MN) and IgA Nephropathy (IgAN) account for 40-45% of all GN (Cattran et al., 2017) and are a common cause of end stage renal disease (Sim et al. 2019). Patients living with end stage renal disease are burdened by the need for lifelong dialysis and/or transplantation. Dialysis is typically required three times weekly for 4 hours per session (National Kidney Foundation, 2020); it carries an increased risk of infection (Wakasugi, 2012), and is associated with 44% mortality at 5 years (Nordio, 2012). Moreover, autoimmunity is unequivocally regarded as the predominant pathogenic process underlying most forms of Glomerulonephritis (Couser, 2014). The ongoing presence of autoantibodies can precipitate recurrence of disease after transplantation, increasing the risk of graft failure (Passerini, 2019; Ponticelli, 2010). Although some patients do not progress to end stage renal disease, they are at an increased risk for life-threatening thrombotic events including deep venous thrombosis, renal vein thrombosis, and pulmonary embolism (Mirrakhimov, 2014).


The manifestations of glomerular diseases  are also associated with significantly impaired Quality of life including physical and mental health, fatigue, sleep impairment and anxiety (Canetta, 2019; Murphy, 2020).


Membranous Nephropathy (MN)

Membranous Nephropathy (MN) is a leading cause of nephrotic syndrome in adults worldwide (Couser, 2017). Nephrotic syndrome refers mainly to the presence of heavy proteinuria (loss of protein greater than 3.5 g/day), low serum albumin and marked edema (Couser 2017; Trujillo, 2019). The natural course of MN is variable and unpredictable. Although 30-40% of patients may experience spontaneous remission, 30% of patients experience persistent proteinuria with long-term preservation of renal function, and another 30%–50% progress to renal failure within 10-15 years (Trujillo, 2019; Heaf, 1999, Troyanov, 2004). Even if patients with nephrotic syndrome do not progress to renal failure, they have an increased risk of life-threatening thromboembolic and cardiovascular events, and are subject to infections (Wagoner, 1983; Heaf, 1999; Lee, 2016).


In the United States, the incidence of MN is estimated at 1.2 per 100,000; about 3,000 adults newly diagnosed every year (Mc Gorgan, 2011). Around 80% of MN cases are primary and mediated by autoantibodies, while 20% are secondary to other diseases. The age of onset is typically 50-60 years old (Couser, 2017).


Anti-phospholipase A2 receptor (PLA2R) antibody positive MN makes up to 85% of all primary Membranous Nephropathy (Trujillo, 2019, Pozdizk, 2018, Couser 2017). PLA2R is a membrane glycoprotein expressed on epithelial cells in glomeruli. In anti-PLA2R antibody-positive MN, patients’ immune system reacts against PLA2R by producing specific autoantibodies. The immune complexes formed by the binding of these autoantibodies to PLA2R induces inflammation, which leads to thickening of the glomerular membrane and cause nephrotic syndrome in 80% of the patients with MN (Couser 2017; Trujillo, 2019; Pozdizk, 2018) (figure 1).


Currently, there is no approved standard treatment for Membranous Nephropathy. The KDIGO guidelines – a global nonprofit organization developing and implementing evidence-based clinical practice guidelines in kidney disease - recommend using criteria such as anti-PLA2R antibody titer and proteinuria to stratify patients by risk and determine course of treatment. The current treatment regimen mainly comprises various non-immunosuppressive drugs (eg ACE inhibitors or Angiotensin receptor blockers, statins, and diuretics), conventional immunosuppressive drugs (e.g. cyclophosphamide combined with steroids, calcineurin inhibitors, mycophenolat-Mofetil) and off-label use of B-cell depleting agents (e.g. anti-CD20 antibodies) (KDIGO 2020; Ronco, 2021).





IgAN, also known as Berger’s disease, is the most prevalent chronic glomerular disease worldwide; it accounts for 27% of renal biopsy (Yim T, 2020, Schena 2018). The clinical and pathological manifestations are highly variable and may include asymptomatic hematuria, massive proteinuria, hypertension, interstitial fibrosis, glomerulosclerosis and a slow progression to chronic kidney disease (Hass, 1997, Rodrigues, 2017, Moriyama, 2014). Although spontaneous remission of IgAN occurs in 10–20% of patients, a minority of cases are considered ‘rapidly progressing IgAN’, defined as an increase in serum creatinine to >1.5 mg/dL; the 5-year renal survival rate in these patients is approximately 30% (Suzuki, 2014; Lv, 2013). Within 20 years of diagnosis, about 40% of patients with IgAN progress to ESRD (Schena et al. 2018). Major risk factors for progression to ESRD are persistent proteinuria, hypertension, and reduced glomerular filtration rate (Fellstroem 2017, Wyatt 2013). Worldwide IgAN incidence is estimated at 2.5 per 100,000 (McGrogan, 2011). IgA nephropathy can affect all ages but is most common in the second and third decades of life.(Wen, 2010).


IgAN is an autoimmune disease of the glomeruli, in which a combination of genetic and environmental factors cause patients to produce galactose-deficient IgA1 (Gd-IgA1; Rodrigues, 2017; Knoppova, 2016). Patients’ immune system reacts against Gd-IgA1 by producing specific autoantibodies. The binding of these IgG autoantibodies to Gd-IgA1 form immune complexes in the circulation, then accumulates in the glomerular mesengium where they induce local inflammation, mesangial proliferation, glomerulosclerosis and loss of renal function (Figure 2; Knoppova, 2016; Rodrigues, 2017).


Management of IgAN is initially focused on non-immunosuppressive strategies, so-called supportive care, to slow the rate of progression of the disease: rigorous blood pressure control, optimal inhibition of the renin angiotensin system, and lifestyle modification, including weight reduction, exercise, smoking cessation, and dietary sodium restriction (KDIGO 2020). If not well-managed, they move on to immunosuppressive treatment.




B-cells provide immunity, and have a key role in autoimmunity, by differentiating into antibody-secreting plasma cells. This differentiation is associated with a change of cell markers. Earlier B-cell stages expressed CD20 marker at their cell surface, while CD38 molecule is highly expressed on differentiated B-cells called plasmablasts and short/long lived-plasma cells. CD38-positive plasma cells are the main source of autoantibodies in autoimmune diseases as they produce quantitatively more autoantibodies than CD20-positive B cells (Bayles, 2014; Jackson, 2015, Halliley, 2016)



Felzartamab specifically binds to the cell surface antigen CD38. Binding of felzartamab to CD38-positive plasma cells facilitates the depletion of such cells via two modes of action: i) antibody-dependent cell-mediated cytotoxicity (ADCC) in which the plasma cells are lysed by Natural killer (NK) cells, and ii) antibody-dependent cell-mediated phagocytosis (ADCP) in which the macrophages clear away the plasma cells  (Endell, 2012; Boxhammer, 2015; Raab, 2020). Since the depletion of antibody producing cells should subsequently lead to a decrease in antibody titers, treatment with felzartamab may be potentially beneficial in autoimmune diseases with a causal relationship between autoantibodies and the disease (Figure 3).



In both MN and IgAN, long-lived plasma cells drive pathogenic antibody production, contributing to functional damage to the glomeruli (Rodrigues, 2017; Ruggenenti, 2015). In IgAN, plasma cells are also the main source of the disease trigger, ie Gd-IgA1 (Rodrigues, 2017).


  • In Membranous Nephropathy, a tight correlation has been described between the clinical course of the disease and PLA2R pathogenic autoantibody titer. Patients with a higher anti-PLA2R autoantibody titer have more severe disease and a longer time to disease remission (Pozdzik, 2018; van de Logt, 2019). High titers and sustained or recurrent positivity for anti-PLA2R antibody titers during therapy emerge as negative predictors for outcome (Bomback 2018; Ruggenenti, 2015). By contrast, a reduction in anti-PLA2R autoantibody levels is predictive of future likelihood of remission of proteinuria (Dahan, 2017; Ruggenenti, 2015). It precedes a reduction in proteinuria and increase in serum albumin (Beck, 2011; Ruggenenti, 2015). Patients presenting with high autoantibody titers are treated with anti-CD20 antibodies (Ruggenent, 2015; Fervenza et al., 2019). However, anti-CD20 therapeutic approaches target only activated B-cells that produce less autoantibodies, and leave C20-negative/CD38-positive long-lived plasma cells, which maintains the autoimmunity. As a result, up to 40% of patients failed to respond to anti-CD20 therapies (Bomback, 2018, Couser 2017). 


In this context, a felzartamab-induced depletion of the main source of pathogenic antibodies, ie the plasma cells, may potentially provide a viable emerging therapeutic option sparing patients of significant toxicity by conventional immunosuppressive agents and possibly improve outcomes for patients with limited benefit of an anti-CD20 directed therapy.


  • In IgAN, high immunological activity is correlated with worse clinical outcomes in patients with IgAN. Serum levels of Gd-IgA1 are associated with risk of decline in renal function and serum levels of anti-Gd-IgA1 antibodies at the time of biopsy are associated with progression to dialysis and death (Berthoux, 2012; Zhao, 2012). High serum levels of Gd-IgA1, anti-Gd-IgA1 and circulating immune complexes are all associated with severity of proteinuria and/or hematuria (Suzuki, 2009; Suzuki, 2019). Current therapeutic options are limited to supportive care or broad-acting immunosuppressive therapies (KDIGO, 2020). As Gd-IgA1-containing immune complexes play a critical role in the pathogenesis of IgAN, a therapeutic intervention that targets the production of Gd-IgA1 and/or the autoantibodies specific to Gd-IgA1 could be an effective disease-specific treatment for IgAN (Knoppova, 2016).

In this context, felzartamab may have a dual action through the depletion of the plasma cells. It may remove both components of the immune complexes, the antigen Gd-IgA1 and the IgG autoantibodies to Gd-IgA1. Hence, felzartamab may potentially be an emerging disease-modifying therapeutic option for patients with IgAN.

Ongoing Clinical Studies in Glomerular Diseases

Phase 2a study: Felzartamab in patients with Anti-PLA2R Antibody-Positive Membranous Nephropathy (aMN) – NewPLACE study (MorphoSys)

Felzartamab is currently under investigation in a Phase 2a, open-label, 2-arm multi-center clinical trial to assess PK/PD, safety and efficacy of the therapeutic antibody in patients with aMN. The clinical trial is conducted at multiple sites in Europe and Asia-Pacific countries. For further details please refer to the following site:

Phase 2a study: Felzartamab in patients with IgA nephropathy (IgAN) – IGNAZ study (MorphoSys)

Felzartamab is currently being evaluated in a Phase 2a, randomized, placebo-controlled, multi-center, double-blind parallel-group clinical trial that assesses the efficacy, safety and pharmacokinetic (PK)/pharmacodynamic (PD) relationship of felzartamab in patients with IgAN. The clinical trial is conducted in Europe, North America and Asia-Pacific countries (including Japan). For further details please refer to the following site: https://clinicaltrials.goc/ct2/show/NCT05065970

Phase 1b/2a study: Felzartamab in patients with Anti-PLA2R Antibody-Positive Membranous Nephropathy (aMN) – M-PLACE study (MorphoSys)

Felzartamab is currently under investigation in a Phase 1b/2a, open-label, multi-center clinical trial to assess the safety and efficacy of the therapeutic antibody in patients with aMN. The clinical trial is conducted at multiple sites in the U.S., Europe, and Asia-Pacific countries. For further details please refer to the following site:

Multiple Myeloma (MM)

Multiple myeloma (MM) is subtype of blood cancer that originates in plasma cells. The malignant cells accumulate in the bone marrow, where they displace and suppress healthy blood progenitor cell populations (Kyle, 2009; Rawstron, 1998). Multiple myeloma is also characterized by destructive lytic bone lesions (rounded, punched-out areas of bone), diffuse osteoporosis, bone pain, and the production of abnormal proteins, which accumulate in the urine (Dispenzieri, 2005; Kyle, 2003). Anemia is also present in most multiple myeloma patients at the time of diagnosis and during follow-up. Anemia in multiple myeloma is multifactorial and is secondary to bone marrow replacement by malignant plasma cells, chronic inflammation, relative erythropoietin deficiency, and vitamin deficiency (Baz, 2004; Bouchnita, 2016).


CD38 is one of the most strongly and uniformly expressed antigens on the surface of malignant plasma cells and is an established diagnostic marker for Multiple myeloma (Jeong, 2012; Flores-Montero, 2016). Binding of felzartamab to CD38 may result in in antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) mediated killing of cancer cells (Raab, 2020). 



Phase 2 study to evaluate the efficacy and safety of MOR202/TJ202 combined with dexamethasone in relapsed/refractory multiple myeloma (I-Mab)

The multi-center, single-arm phase 2 study to evaluate the efficacy and safety of MOR202/TJ202 combined with dexamethasone in patients with relapsed or refractory multiple myeloma is conducted by I-Mab Biopharma. The trial enrolls patients in mainland China and Taiwan who received at least 2 prior lines of treatment of which one treatment must include a proteasome inhibitor and an immunomodulator. All patients will receive MOR202/TJ202 and dexamethasone (Dex) in the study. The primary endpoint of the study is overall response rate, secondary outcome measures are amongst others duration of response, time-to-progression, and progression-free survival. The treatment will continue until endpoint events such as intolerance or progressive disease. The study has been designed as a pivotal trial, which, if successful, could lead to a biologics license application (BLA) in Greater China.

Phase 3 study to evaluate the efficacy and safety of MOR202/TJ202 combined with leanalidomide in relapsed/refractory multiple myeloma (I-Mab)

The randomized, open-label, parallel-controlled, multicenter phase 3 study will be conducted by I-Mab in mainland China and Taiwan to evaluate the efficacy and safety of the combination of MOR202/TJ202 plus lenalidomide (LEN) and dexamethasone (DEX) versus the combination of LEN and DEX in patients with relapsed or refractory multiple myeloma who received at least one prior line of treatment. The primary endpoint is to evaluate the progression-free survival (PFS) comparing the efficacy of MOR202/TJ202 plus LEN/DEX versus LEN/DEX. The study has been designed as a pivotal trial, which, if successful, could lead to a biologics license application (BLA) in Greater China.

Disclaimer: MorphoSys’ product candidates are investigational and are currently not approved for the treatment of any disease or condition anywhere in the world. They cannot be prescribed or purchased for therapy at present. The MorphoSys website may contain information on drug candidates and clinical trials sponsored by MorphoSys with the intention of increasing the transparency of the company’s clinical research. There is no guarantee any product will be approved in the sought-after indication. Information contained within this website is not intended to replace the advice of a healthcare professional and should not be considered as a recommendation. Patients should always seek medical advice before making any decisions on their treatment. All reasonable precautions have been taken to ensure the accuracy, security, and confidentiality of information available through the site. MorphoSys may amend the information at any time without notice.


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