felzartamab (MOR202) / TJ Biopharma, Novartis, Biogen - LARVOL DELTA

Whole-Blood RNA Sequencing (RNAseq) Profiling Identifies Functionally Enriched Gene Expression Patterns in Felzartamab-Treated Patients with IgAN: Data from the Phase 2 IGNAZ Study (KIDNEY WEEK 2025) - P2 | "Conclusion Felzartamab treatment-related gene expression changes detected by whole blood RNAseq are functionally enriched for CD38 + cell types, including immunoglobulin and IgA-related genes, supporting targeting and reduction of plasma cells in IgAN. These results validate the use of this dataset for further analyses to understand the mechanism of action of felzartamab and to further characterize felzartamab treatment response in patients with IgAN."

Clinical • IO biomarker • P2 data • Glomerulonephritis • IgA Nephropathy • Renal Disease

PROMINENT: An Open-Label, Randomized Phase 3 Trial of Felzartamab in Primary Membranous Nephropathy (KIDNEY WEEK 2025) - P3 | "PROMINENT (NCT06962800) is an open-label, multicenter, randomized Phase 3 study in which 180 adults with newly diagnosed or relapsed biopsy-confirmed PMN in need of immunosuppressive therapy will be randomized to IV felzartamab or oral tacrolimus in protocol-specified dosing regimens. Participants who experience worsening kidney function or proteinuria, relapse, or do not improve on assigned treatment can receive rescue treatment. PROMINENT is the first Phase 3 trial evaluating the targeting of CD38 + plasma cells and plasmablasts in PMN to reduce proteinuria and preserve kidney function, which may address an unmet need in a disease with no approved therapies."

Clinical • P3 data • Glomerulonephritis • Immunology • Nephrology • Renal Disease

PREVAIL: A Phase 3 Trial of Felzartamab in Adults with IgAN (KIDNEY WEEK 2025) - P3 | "PREVAIL is the first Phase 3 trial investigating CD38 + targeting in IgAN. The results will further inform on the safety and efficacy of this novel therapy with the potential to specifically target the pathogenic cellular drivers of IgAN and disease relevant antibody production."

Clinical • P3 data • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease

Preservation of Humoral Immunity and Response to Vaccination and Infection in Felzartamab-Treated Patients with IgAN: Data from the Phase 2 IGNAZ Study (KIDNEY WEEK 2025) - P2 | "Conclusion Patients with IgAN receiving felzartamab demonstrated preservation of humoral immunity, which may contribute to a favorable safety profile versus other B-cell targeting therapies. These findings are consistent with those previously observed in PMN."

Clinical • P2 data • Glomerulonephritis • IgA Nephropathy • Infectious Disease • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases • Tetanus

TRANSPIRE: A Phase 2 Trial Evaluating the Efficacy and Safety of Felzartamab in Kidney Transplant Recipients with Late Isolated Microvascular Inflammation (KIDNEY WEEK 2025) - "Safety will be assessed throughout the study. TRANSPIRE is the first clinical trial designed to investigate a targeted therapy in kidney transplant recipients with late isolated MVI."

Clinical • P2 data • Antibody-mediated Rejection • Inflammation • Transplantation

TRANSCEND: A Phase 3 Trial of the Anti-CD38 Antibody Felzartamab in Kidney Transplant Recipients with Late Antibody-Mediated Rejection (KIDNEY WEEK 2025) - P3 | "TRANSCEND is the first Phase 3 trial evaluating the concept of CD38 targeting in AMR after kidney transplant. Results from this study may provide a novel treatment option and potentially transformative therapy for this challenging condition of high unmet medical need."

Clinical • P3 data • Antibody-mediated Rejection • Inflammation • Transplantation

IMMUNOLOGICAL AND HISTOLOGICAL REVERSAL OF REFRACTORY ABMR WITH DARATUMUMAB IN PEDIATRIC KIDNEY TRANSPLANTATION (ESPN 2025) - " Two pediatric patients were included in a non-randomized pilot study assessing the safety and efficacy of daratumumab as rescue therapy for refractory ABMR to conventional therapy (SOC: immunoadsorption, IGIV and rituximab). Our preliminary data suggest that daratumumab is a safe treatment with a promising response for refractory ABMR and chronic active ABMR, associated with a significant recovery of active microvascular inflammatory lesions and downregulating circulating DSA. Further studies may help to determine whether maintenance therapy or repeated courses are required, and to assess the long-term impact on graft function and survival. References 1 Mayer KA, Schrezenmeier E, Diebold M, et al, A Randomized Phase 2 Trial of Felzartamab in Antibody-Mediated Rejection."

Clinical • Antibody-mediated Rejection • Inflammation • Pediatrics • Transplantation • NCOA4

TRANSPIRE: A Study to Learn About the Effects of Felzartamab Infusions on Adults With Kidney Transplants Who Have Late Isolated Microvascular Inflammation (clinicaltrials.gov) - P2 | N=81 | Not yet recruiting | Sponsor: Biogen

New P2 trial • Inflammation • Transplantation

Treatment of Plasma Cell Disorders Post Solid Organ Transplant – A Positive Single Center Experience using Immunomodulatory Drugs (IMS 2025) - "Data collected included transplant type, treatment details & patient & allograft outcomes. 7 patients met the inclusion criteria: 4 received IMiD, lenalidomide 5mg, 1 patient also received pomalidomide & 3 patients received no IMiDs, serving as a comparison group...There was no rejection documented in all patients.CaseAgeSexHLA Mismatch (DSA)Haematological DiagnosisTransplant to IMiD (Years)Time on IMiD (Years)Haematological response to IMiD IS161F3LCDD--VGPRPred 5, Tac (6-8), MPA 360mg BD264M3AL Amyloidosis--VGPRPred 5, Tac (6-7), MMF 1g BD372FUnknownMM--VGPRTac (5-6), MMF 500mg BD467M0SM54VGPRTac (1-3)569M6 (A2)MM53VGPRPred 5, Tac (6-7), MMF 1g BD682M1MM153VGPRPred 5, Tac (4-6), MMF 250mg BD757F6 (Moderate A2, A24)MM70.5No responsePred 5/25, TacTable 1: Patient characteristics, hematologic response & allograft outcomes (MMF: mycophenolate mofetil, MPA: mycophenolic acid, Pred: prednisone, SM: Smouldering myeloma, Tac: Tacrolimus (target level), VGPR:..."

Clinical • Immunomodulating • Amyloidosis • Antibody-mediated Rejection • Hematological Malignancies • Immunology • Multiple Myeloma • Solid Organ Transplantation • Transplant Rejection • Transplantation • IFNG • IL2

Histological Reversal of Refractory ABMR with Daratumumab in Kidney Transplant Patients (WTC 2025) - "Anti-CD38 therapies, targeting plasma cells, some mature B-cell subsets, and NK cells, may have a beneficial therapeutic effect in ABMR, as recently shown with Felzartamab. * We designed a non-randomized pilot study assessing the safety and efficacy of daratumumab as rescue therapy for refractory ABMR to conventional therapy (PE, IVIG and/or rituximab)... Our preliminary data strongly suggest that daratumumab treatment for refractory ABMR is associated with a significant recovery of active microvascular inflammatory lesions of ABMR and a reduction of circulating DSA. Mechanistic studies will bring deeper insight on the mechanisms of action of the drug."

Clinical • Antibody-mediated Rejection • Glomerulonephritis • Infectious Disease • Inflammation • Nephrology • Pneumonia • Respiratory Diseases • Septic Shock • Transplantation

Felzartamab: a magic bullet to treat microvascular rejection? (PubMed, Kidney Int) - No abstract available

Journal • Antibody-mediated Rejection • Inflammation • Transplant Rejection • Transplantation

TRANSCEND: A Phase 3 Trial of the Anti-CD38 Antibody Felzartamab in Kidney Transplant Recipients with Late Antibody-Mediated Rejection (WTC 2025) - P3 | "TRANSCEND is the first Phase 3 trial evaluating the concept of CD38 targeting in AMR after kidney transplantation. Results from this study may provide a novel treatment option and potentially transformative therapy for this challenging condition of high unmet medical need."

Clinical • P3 data • Antibody-mediated Rejection • Inflammation • Transplantation

Phase 2 study of felzartamab, an investigational anti-CD38 monoclonal antibody, in AMR (WTC 2025) - "Sponsored by Biogen"

P2 data

ISS 16 – AMR Pathogenesis of the Kidney: The Central Role of CD38+ Cells (WTC 2025) - "Sponsored by Biogen This symposium will review the following topics around antibody-mediated rejection of the kidney: Treatment landscape & unmet need AMR disease state, with a focus on how CD38+ cells might contribute to AMR pathogenesis Targeting of CD38+ cells in AMR Molecular impact of felzartamab, an investigational anti-CD38 monoclonal antibody, in AMR"

Antibody-mediated Rejection • CD38

Phase III PROMINENT Trial Initiated to Evaluate Felzartamab for Primary Membranous Nephropathy (Appl Clin Trials) - "The 104-week, randomized, open-label, global, multicenter Phase III PROMINENT trial will compare the efficacy and safety of felzartamab vs. tacrolimus in producing complete remission of proteinuria in patients with moderate-to-high-risk PMN, including both newly diagnosed and relapsed participants. Investigators anticipate enrolling approximately 180 patients with PMN and project readout in 2029."

P3 data • Trial status • Immunology • Nephrology • Renal Disease

Randomized, Double-Blind, Placebo-Controlled Phase 2a Study Assessing the Efficacy and Safety of Felzartamab for IgA Nephropathy. (PubMed, Kidney Int) - P2 | "Our study shows treatment with felzartamab results in sustained reduction of proteinuria, suggesting disease improvement. Further evidence is needed to understand the impact of felzartamab on preservation of kidney function in high-risk patients with IgAN."

Clinical • Journal • P2a data • Glomerulonephritis • IgA Nephropathy • Renal Disease

TREATMENT OF PLASMA CELL DISORDERS POST SOLID ORGAN TRANSPLANT - A POSITIVE SINGLE CENTER EXPERIENCE USING IMMUNOMODULATORY DRUGS (EHA 2025) - "Seven patients met the inclusion criteria, of which four patients were treated with IMiD, low dose lenalidomide 5mg; one patient also received pomalidomide for two months...Most patients had a very good partial response (VGPR); a complete response was suspected in 5 patients but could not be confirmed due lack of confirmatory bone marrow biopsy.(Table 1: Patient characteristics, hematologic response and allograft outcomes (MMF: mycophenolate mofetil, MPA: mycophenolic acid, Pred: prednisone, SM: Smouldering myeloma, Tac: Tacrolimus (target level), VGPR: Very Good Partial Response) Summary/ In this limited case series with long-term follow up, IMiD use in SOT recipients was not associated with SOTr and resulted in hematologic VGPR in three out of four patients.This contrasts with the majority of existing literature, which suggests a plausible risk of SOTr as IMIDs induce T-cell proliferation, enhance interleukin-2 and interferon-gamma production and inhibit regulatory..."

Clinical • Immunomodulating • Amyloidosis • Antibody-mediated Rejection • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology • Solid Organ Transplantation • Transplant Rejection • Transplantation • IFNG • IL2

Monitoring Anti-CD38 Treatment with Felzartamab in Antibody-Mediated Kidney Allograft Rejection (ERA 2025) - "These results suggest that dd-cfDNA, may serve as a useful biomarker for monitoring early response to felzartamab treatment. More importantly, dd-cfDNA could indicate the recurrence of rejection after treatment cessation in a timely none-invasive manner, which is subject to ongoing investigations"

IO biomarker • Antibody-mediated Rejection • Inflammation • Transplant Rejection • CXCL10 • CXCL9

Felzartamab in humoral rejection: an update (ERA 2025) - No abstract available

Antibody-mediated Rejection

Effect of felzartamab anti-CD38 treatment on the molecular phenotype of antibody-mediated rejection in kidney transplant biopsies (ERA 2025) - "Felzartamab selectively suppressed IFNG-inducible and NK cell transcripts, offering parenchymal benefits and potentially slowing progression to kidney failure despite near-universal molecular recurrence by week 52."

Biopsy • Antibody-mediated Rejection • Renal Disease • Transplantation • IFNG

PROMINENT: A Study to Learn More About the Effects and Safety of Felzartamab Infusions in Adults With Primary Membranous Nephropathy (PMN) (clinicaltrials.gov) - P3 | N=180 | Recruiting | Sponsor: Biogen | Not yet recruiting ➔ Recruiting

Enrollment open • Glomerulonephritis • Renal Disease

Targeting CD38 in Antibody-Mediated Rejection. (PubMed, Transpl Int) - "This review focuses on recent results from CD38-targeted therapies, with felzartamab emerging as a promising option. Previous case reports and series suggested that off-label daratumumab treatment could effectively reverse AMR...The potential benefits of prolonged therapy are currently being investigated in a recently launched phase III trial. Future studies may expand the applications of CD38 targeting to early AMR or broader indications, such as DSA-negative microvascular inflammation."

Journal • Review • Antibody-mediated Rejection • Inflammation • Transplantation

Antibody-mediated Rejection - Treatment Standard. (PubMed, Nephrol Dial Transplant) - "We conclude that steroids, rituximab, bortezomib, and interleukin-6 (IL-6) antagonists lack sufficiently robust evidence to support their use in AMR. Along these lines, in severe early AMR, complement inhibition may also be an option. Ongoing phase 2 trials evaluating prolonged courses of high dose IVIG, the neonatal Fc receptor blocker efgartigimod, the tyrosine kinase inhibitor fostamatinib, and the complement inhibitor BIVV020, along with phase 3 trials of the anti-IL-6 receptor antibody tocilizumab and the CD38 antibody felzartamab, offer hope for effective, approved therapies targeting different aspects of AMR pathobiology."

Journal • Antibody-mediated Rejection • Inflammation • Transplantation

PREVAIL: A Study to Learn About the Effects of Felzartamab Infusions on Adults With Immunoglobulin A Nephropathy (IgAN) (clinicaltrials.gov) - P3 | N=454 | Recruiting | Sponsor: Biogen | Not yet recruiting ➔ Recruiting

Enrollment open • Glomerulonephritis • IgA Nephropathy • Renal Disease

PROMINENT: A Study to Learn More About the Effects and Safety of Felzartamab Infusions in Adults With Primary Membranous Nephropathy (PMN) (clinicaltrials.gov) - P3 | N=180 | Not yet recruiting | Sponsor: Biogen

New P3 trial • Glomerulonephritis • Renal Disease