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

Enhanced Prenatal and Postnatal Development Study in Marmoset Monkeys Following Administration of Felzartamab. (PubMed, Int J Toxicol) - "Among infants, there were no felzartamab-related malformations or variations in external anatomy or skeletal morphology and no felzartamab-related observations in histopathology, hematologic and immune cell development, or humoral immune response to vaccination. In conclusion, among pregnant marmoset monkeys dosed with felzartamab, the lack of reproductive toxicity and felzartamab-related effects on offspring supports the clinical evaluation of felzartamab in women of childbearing potential and further demonstrates the suitability of the marmoset monkey for ePPND studies."

IO biomarker • Journal • Hematological Disorders

TRANSCEND: A Trial of Felzartamab in Kidney Transplant Recipients With Late Antibody-Mediated Rejection (AMR) (clinicaltrials.gov) - P3 | N=120 | Not yet recruiting | Sponsor: HI-Bio, A Biogen Company

New P3 trial • Antibody-mediated Rejection • Transplantation

Felzartamab Durably Reduces Disease-Relevant Biomarkers through Targeting of CD38+ Plasma Cells and Plasmablasts, the Upstream Drivers of IgAN (KIDNEY WEEK 2024) - P2 | "Felza targets and depletes the upstream cellular drivers of IgAN resulting in rapid reduction of major disease related biomarkers. Effects are maintained off-treatment while also preserving humoral immunity. These observations are consistent with other indications, supporting the disease modifying potential of felza in immune mediated diseases."

Biomarker • IO biomarker • Glomerulonephritis • IgA Nephropathy • Immunology

Felzartamab for IgA Nephropathy: Final Results of the IGNAZ Study (KIDNEY WEEK 2024) - "Felzartamab was generally well tolerated and led to sustained proteinuria reduction and reduced eGFR decline vs PBO, indicating potential disease modification in patients with IgAN. Investigation of felzartamab in patients at high risk for loss of kidney function is warranted."

Clinical • Late-breaking abstract • Glomerulonephritis • IgA Nephropathy • Immunology • Infectious Disease • Renal Disease

Felzartamab Selectively and Potently Targets CD38+ Antibody-Secreting Cells from Patients with Immune-Mediated Kidney Diseases (KIDNEY WEEK 2024) - "These in vitro and in vivo proof of concept studies highlight the capacity of felza to selectively deplete CD38+ ASC, suggesting the potential for clinical utility in antibody-driven IMD. Clinical trials assessing the safety and efficacy of felza in immune-mediated kidney diseases including MN, IgAN, antibody-mediated kidney rejection and lupus nephritis are currently ongoing."

Clinical • Antibody-mediated Rejection • Glomerulonephritis • IgA Nephropathy • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • CD34

Biogen Receives U.S. FDA Breakthrough Therapy Designation for Felzartamab for the Treatment of Antibody-Mediated Rejection in Kidney Transplant Recipients (GlobeNewswire) - "Biogen Inc...announced today that felzartamab, an investigational anti-CD38 monoclonal antibody, has received Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration (FDA) for the treatment of late antibody-mediated rejection (AMR) without T-cell mediated rejection in kidney transplant patients....Biogen plans to initiate Phase 3 trials for felzartamab across AMR, IgAN, and PMN in 2025."

Breakthrough therapy • New P3 trial • Antibody-mediated Rejection • IgA Nephropathy • Immunology • Nephrology • Transplant Rejection

Cancelled: Evaluation of Neutralizing Agent – DaraEx – to Combat Anti-CD38 Serologic Interference (AABB 2024) - "Another method of removing the anti-CD38 serologic interference is the imusyn DaraEx (For Research Use Only) neutralizing agent, which inhibits the agglutination effect of the anti-CD38 antibodies Daratumumab, Felzartamab, and Isatuximab in the IAT, and does not cause any red cell antigen destruction.Study Design/ Ten previously identified anti-CD38 patients referred to the IRL for antibody consultation were tested in parallel with the current procedure of DTT treatment of the red cells and with the new DaraEx neutralizing reagent. Both methods, 0.2M DTT and DaraEx, proved to be effective at removing the anti-CD38 serologic interference. DaraEx appears to be the more favorable option in situations when a patient phenotypes cellano or Kpb negative, or when using the Gel column technique to accommodate smaller sample volumes. Taking cost into consideration, the use of DaraEx over 0.2M DTT treatment as the primary method, to routinely remove the anti-CD38 interference in..."

Hematological Disorders • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

Felzartamab in Antibody-Mediated Rejection. (PubMed, N Engl J Med) - No abstract available

Journal • Antibody-mediated Rejection

Felzartamab in Antibody-Mediated Rejection. (PubMed, N Engl J Med) - No abstract available

Journal • Antibody-mediated Rejection

Felzartamab in Antibody-Mediated Rejection. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Antibody-mediated Rejection

A Study of Felzartamab in Participants With Lupus Nephritis (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: HI-Bio | Trial completion date: May 2025 ➔ Jun 2026 | Trial primary completion date: May 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody-Positive Primary Membranous Nephropathy. (PubMed, Kidney Int Rep) - P1/2 | "Serum albumin increased from baseline to EOS in 20 of 26 patients (76.9%) (C1, 12/15 [80.0%]; C2, 8/11 [72.7%]). In this population with high-risk anti-PLA2R+ PMN, felzartamab was tolerated and resulted in rapid partial and complete immunologic responses and partial improvements in proteinuria and serum albumin in some patients."

Journal • P1/2 data • Glomerulonephritis • Renal Disease

Study of Felzartamab in Healthy Adult Subjects (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: TJ Biopharma Co., Ltd. | Recruiting ➔ Completed | N=60 ➔ 24 | Trial completion date: Dec 2024 ➔ Aug 2024 | Trial primary completion date: Dec 2024 ➔ Aug 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date

Chronic Rejection After Kidney Transplantation. (PubMed, Transplantation) - "However, several promising therapies are currently under investigation, including felzartamab, a monoclonal antibody targeting the surface molecule CD38, which is highly expressed in NK cells and antibody-producing plasma cells. In an exploratory phase 2 trial in late AMR, this compound has demonstrated potential in resolving molecular and morphologic rejection activity and injury, predominantly by targeting NK cell effector function. These findings inspire hope for effective treatments and emphasize the necessity of further pivotal trials focusing on chronic transplant rejection."

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

Donor-Derived Cell-Free DNA as a Companion Biomarker for AMR Treatment With Daratumumab: Case Series. (PubMed, Transpl Int) - "While there are no approved therapies, several case reports with daratumumab and the very recent phase 2 trial of felzartamab in AMR have indicated the potential efficacy of therapeutic interventions targeting CD38. In both patients, daratumumab treatment led to stabilization of kidney function parameters, a strong decline of dd-cfDNA below the previously established threshold for rejection, and partial or complete histologic resolution of AMR activity. Our case series suggests that dd-cfDNA may be a useful companion biomarker for longitudinal monitoring of anti-CD38 treatment in patients with AMR."

Biomarker • IO biomarker • Journal • Antibody-mediated Rejection • Transplantation

TJ202, Lenalidomide and Dexamethasone vs. Lenalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P3 | N=289 | Completed | Sponsor: TJ Biopharma Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Hematological Malignancies • Multiple Myeloma • Oncology

Randomized phase trial of felzartamab in humoral transplant rejection (TTS 2024) - "Felzartamab exhibited favorable safety and efficacy, underscoring its potential as a novel therapeutic option in ABMR."

Clinical • IO biomarker • Antibody-mediated Rejection • Immunology • Inflammation • Transplant Rejection • Transplantation

Felzartamab and Antibody-Mediated Rejection in Kidney Transplants - Hope at Last? (PubMed, N Engl J Med) - No abstract available

Journal • Antibody-mediated Rejection • Transplantation

IGNAZ: Clinical Trial to Assess Efficacy and Safety of the Human Anti-CD38 Antibody Felzartamab (MOR202) in IgA Nephropathy (clinicaltrials.gov) - P2 | N=54 | Completed | Sponsor: HI-Bio | Active, not recruiting ➔ Completed

Trial completion • Glomerulonephritis • IgA Nephropathy • Renal Disease

A Randomized Phase 2 Trial of Felzartamab in Antibody-Mediated Rejection. (PubMed, N Engl J Med) - P2 | "Felzartamab had acceptable safety and side-effect profiles in patients with antibody-mediated rejection. (Funded by MorphoSys and Human Immunology Biosciences; ClinicalTrials.gov number, NCT05021484; and EUDRACT number, 2021-000545-40.)."

IO biomarker • Journal • P2 data • Antibody-mediated Rejection • Inflammation • Transplantation

Randomized Phase 2 Trial of Felzartamab in Humoral Transplant Rejection (ERA-EDTA 2024) - "Felzartamab exhibited a favorable safety and efficacy profile, underscoring its potential as a novel therapeutic option in ABMR."

Clinical • IO biomarker • Late-breaking abstract • P2 data • Antibody-mediated Rejection • Immunology • Inflammation • Transplant Rejection • Transplantation

Felzartamab (anti-CD38) in Patients with IgA Nephropathy - Interim Results from the IGNAZ Study (ERA-EDTA 2024) - "This proof-of-concept study highlights the potential for disease modification in IgAN with the anti-CD38 mAb felza and supports continued research as a potential treatment for high-risk IgAN patients. Felza treatment resulted in clinically meaningful, prolonged UPCR reductions and eGFR stabilization sustained ≥10 months after dosing was completed. Felza was generally well tolerated with rapid recovery of IgG with durable reductions in IgA and pathogenic Gd-IgA1 levels."

Clinical • IO biomarker • Antibody-mediated Rejection • Chronic Kidney Disease • Glomerulonephritis • IgA Nephropathy • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Renal Disease

HI-Bio Presents Positive Interim Results from Phase 2 IGNAZ Study of Felzartamab in IgA Nephropathy at 61st European Renal Association (ERA) Congress (PRNewswire) - P2 | N=54 | IGNAZ (NCT05065970) | Sponsor: HI-Bio | "Human Immunology Biosciences...today announced positive interim results from the randomized, placebo-controlled Phase 2 IGNAZ study of the investigational CD38 antibody felzartamab in the treatment of IgA nephropathy (IgAN)....Patients receiving a nine-dose regimen over five months experienced a deep and durable decrease in proteinuria levels, reaching up to ~50% mean reduction in UPCR at month 24, which was more than 18 months after the last dose....Patients were enrolled with proteinuria (UPCR) of at least 1.0 g/d and eGFR of at least 30 ml/min/1.73 m2 and were assigned to one of four groups receiving either placebo, two doses, five doses or nine doses over a 24-week treatment phase of 16 mg/kg of felzartamab provided by intravenous infusion."

P2 data • IgA Nephropathy

Biogen Bolsters Late-Stage Pipeline, Expands Immunology Portfolio with Agreement to Acquire Human Immunology Biosciences (Biogen Press Release) - "Biogen Inc...and Human Immunology Biosciences...today announced the companies have entered into a definitive agreement under which Biogen has agreed to acquire HI-Bio for $1.15 billion upfront and up to $650 million in potential milestone payments....Biogen seeks to retain expertise and talent from HI-Bio and establish a San Francisco Bay Area team focused on expanding our efforts in immune-mediated diseases....In addition to lead program felzartamab, the HI-Bio pipeline includes izastobart/HIB210, an anti-C5aR1 antibody currently in a Phase 1 trial and with potential for continued development in a range of complement-mediated diseases. HI-Bio also has discovery stage mast cell programs with potential in a range of immune-mediated diseases."

M&A • IgA Nephropathy • Immunology

Felzartamab in Late Antibody-Mediated Renal Allograft Rejection (ATC 2024) - P2 | "Based on the hypothesis that felzartamab can counteract ABMR by targeting antibody-producing cells and NK cells, this trial could have the potential to offer the first proof of concept for an effective new anti-rejection therapy."

Late-breaking abstract • Antibody-mediated Rejection • Transplant Rejection • Transplantation