mezagitamab (TAK-079) / Takeda, Xoma, BioInvent - LARVOL DELTA

Safety, Tolerability, and Efficacy of Mezagitamab (TAK-079) as Add-on to Standard of Care Therapy in Individuals with Primary IgA Nephropathy: Results from a Phase 1b Study (ERA 2025) - No abstract available

Clinical • P1 data • Glomerulonephritis • IgA Nephropathy • Renal Disease

BioInvent Receives Milestone Payment as Takeda moves mezagitamab into Phase 3 (ACCESSWIRE) - "BioInvent International AB...today announces that it has earned a 1 million USD milestone payment, following Takeda's...initiation of Phase 3 clinical trial of mezagitamab (TAK-079), identified from BioInvent's proprietary n-CoDeR antibody library. The study is evaluating this potential best-in-class anti-CD83 monoclonal antibody for persistent or chronic primary immune thrombocytopenia (ITP)."

Financing • Immune Thrombocytopenic Purpura

Antigen masking indirect antiglobulin test can mitigate the interference of Mezagitamab, a novel anti-CD38 antibody, in serological pre-transfusion testing. (PubMed, Transfus Med) - "All novel anti-CD38 antibodies, such as mezagitamab, have the potential to interfere in serological pre-transfusion testing. While masking only one epitope, DaraEx has so far been an effective mitigation for all clinical anti-CD38 antibodies."

Journal • CNS Disorders • Hematological Malignancies • Multiple Myeloma • Myasthenia Gravis • Oncology

TAK-079-3002: A Study of Mezagitamab in Adults With Chronic Primary Immune Thrombocytopenia (clinicaltrials.gov) - P3 | N=171 | Recruiting | Sponsor: Takeda | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Takeda Delivers Strong Third-Quarter FY2024 Results; Raises Full Year Outlook, Forecasting Revenue and Core Operating Profit Margin Growth (Businesswire) - "Among the multiple late-stage programs presented, the company expects...Phase 3 data readouts in the calendar year 2025 with filings anticipated in FY2025-FY2026 for the following programs and indications: oveporexton (TAK-861) for the treatment of narcolepsy type 1; zasocitinib for the treatment of psoriasis...Moreover, five additional indication filings for late-stage programs are on pace for FY2027-FY2029. zasocitinib for the treatment of psoriatic arthritis; mezagitamab for treatments of immune thrombocytopenia (ITP), a rare immune-mediated bleeding disorder, and immunoglobulin A nephropathy (IgAN), a chronic progressive autoimmune mediated kidney disease; fazirsiran for the treatment of alpha-1 antitrypsin deficiency-associated liver disease, and elritercept for the treatment of anemia associated with myelodysplastic syndrome."

Filing • P3 data • Alpha-1 Antitrypsin Deficiency • Anemia • IgA Nephropathy • Immune Thrombocytopenic Purpura • Narcolepsy • Psoriasis • Psoriatic Arthritis

A Study to Evaluate Subcutaneous TAK-079 Added to Standard of Care Regimens in Participants With Newly Diagnosed Multiple Myeloma (NDMM) (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: Takeda | Trial completion date: Feb 2025 ➔ Mar 2026 | Trial primary completion date: Feb 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Transplantation

Takeda Spotlights High-Value, Late-Stage Pipeline Accelerating the Development of Potential Transformative Treatments for Patients in Multiple Therapeutic Areas (Businesswire) - "Data from...Phase 3 programs is expected to read out in 2025...zasocitinib, an investigational next-generation, highly selective and potent oral allosteric tyrosine kinase 2 (TYK2) inhibitor will deliver Phase 3 results in psoriasis...Filings for these...indications are expected in fiscal years 2025 and 2026. Five additional indication filings for late-stage programs are on pace for fiscal years 2027 through 2029: zasocitinib in psoriatic arthritis; mezagitamab, an investigational anti-CD38 antibody providing rapid, selective and sustained depletion of disease-causing immune cells that could set a new standard for the treatment of immune thrombocytopenia (ITP) and immunoglobulin A neuropathy (IgAN)."

Filing • P3 data • Immune Thrombocytopenic Purpura • Psoriasis • Psoriatic Arthritis

A Study of Mezagitamab in Adults With Chronic Primary Immune Thrombocytopenia (clinicaltrials.gov) - P3 | N=171 | Not yet recruiting | Sponsor: Takeda

New P3 trial • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Safety, Tolerability, and Efficacy of Mezagitamab (TAK-079) as Add-On to Standard of Care Therapy in Individuals with Primary IgA Nephropathy: Interim Results from an Open-Label Phase 1b Study (KIDNEY WEEK 2024) - P1 | "Mezagitamab was generally well tolerated as an add-on to standard of care therapy. Rapid and sustained reductions in UPCR, serum IgA, and Gd-IgA1 levels were seen with stable eGFR."

Clinical • P1 data • Glomerulonephritis • IgA Nephropathy • Infectious Disease • Lupus Nephritis • Pain • Renal Disease • Respiratory Diseases

A Study of TAK-079 in Adults With Persistent/Chronic Primary Immune Thrombocytopenia (clinicaltrials.gov) - P2 | N=41 | Completed | Sponsor: Takeda | Active, not recruiting ➔ Completed | Trial completion date: Aug 2024 ➔ Apr 2024 | Trial primary completion date: Aug 2024 ➔ Apr 2024

Trial completion • Trial completion date • Trial primary completion date • Hematological Disorders • Immune Thrombocytopenic Purpura • Thrombocytopenia • Thrombocytopenic Purpura

Safety, tolerability, and efficacy of mezagitamab (TAK-079) in chronic or persistent primary immune thrombocytopenia: Interim results from a phase 2, randomized, double-blind, placebo-controlled study (ISTH 2024) - "Participants (N=41) had a mean disease duration of 10.98 (range:0.3–35.2) years and received a mean of 3.9 (range:1–13) prior ITP treatments. In the prespecified interim analysis, TEAE incidence was similar between mezagitamab-treated and placebo-treated participants. In mezagitamab-treated versus placebo groups, 14.3% versus 0%, 17.9% versus 23.1%, and 14.3% versus 7.7% of participants had TEAEs leading to discontinuation, Grade ≥3 TEAEs, and serious adverse events, respectively."

Clinical • Late-breaking abstract • P2 data • Hematological Disorders • Immunology • Thrombocytopenia • Thrombocytopenic Purpura

Takeda Presents Late-Breaking Data from Phase 2b Study of Mezagitamab, Demonstrating Potential to Transform Treatment of Primary Immune Thrombocytopenia (Businesswire) - P2b | N=41 | NCT04278924 | Sponsor: Takeda | "These data (Abstract #LB 01.1) were presented at the oral Late-Breakthrough Session at the 32nd Congress of the International Society on Thrombosis and Haemostasis (ISTH)....The Phase 2b trial results demonstrated that mezagitamab treatment improved platelet response compared to placebo, across all three dose levels of mezagitamab tested....All the different measures of platelet response evaluated were highest among patients treated with the mezagitamab 600mg dose, specifically 81.8% achieved complete platelet response, 90.9% clinically meaningful platelet response, and 100% hemostatic platelet response. Fewer mezagitamab-treated patients compared to placebo had ≥1 disease activity-related bleeding AE (17.9% vs 46.2%, respectively)....'Based on these results, we plan to initiate a Phase 3 study of mezagitamab in ITP in the second half of FY2024'."

Late-breaking abstract • New P3 trial • P2b data • Thrombocytopenia

A Study to Evaluate Subcutaneous TAK-079 Added to Standard of Care Regimens in Participants With Newly Diagnosed Multiple Myeloma (NDMM) (clinicaltrials.gov) - P1 | N=50 | Active, not recruiting | Sponsor: Takeda | Phase classification: P1b ➔ P1 | Trial completion date: Feb 2024 ➔ Feb 2025 | Trial primary completion date: Feb 2024 ➔ Feb 2025

Combination therapy • Phase classification • Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Transplantation

A Study to Evaluate the Safety, Pharmacokinetics (PK), and Pharmacodynamics (PD) of TAK-079 in Combination With Standard Background Therapy in Participants With Moderate to Severe Systemic Lupus Erythematosus (SLE) (clinicaltrials.gov) - P1 | N=23 | Completed | Sponsor: Millennium Pharmaceuticals, Inc. | N=58 ➔ 23 | Phase classification: P1b ➔ P1

Combination therapy • Enrollment change • Phase classification • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Mezagitamab in systemic lupus erythematosus: clinical and mechanistic findings of CD38 inhibition in an autoimmune disease. (PubMed, Lupus Sci Med) - "Mezagitamab had a favourable safety profile in patients with moderate to severe SLE and elicited a pharmacodynamic effect consistent with CD38+ cell depletion. These findings reveal novel insights into the drug's mechanism of action and support the continued investigation of mezagitamab in autoimmune diseases."

IO biomarker • Journal • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Study of TAK-079 in Adults With Persistent/Chronic Primary Immune Thrombocytopenia (clinicaltrials.gov) - P2 | N=41 | Active, not recruiting | Sponsor: Takeda | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura

A Study Of TAK-981 Given With Monoclonal Antibodies (mAbs) In Adults With Relapsed or Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov) - P1/2 | N=27 | Terminated | Sponsor: Takeda | Phase classification: P1b/2 ➔ P1/2 | Active, not recruiting ➔ Terminated; Enrolment Challenges

Combination therapy • Phase classification • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology

A Study of Mezagitamab in Adults With Primary Immunoglobulin A Nephropathy Receiving Stable Background Therapy (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: Takeda | Phase classification: P1b ➔ P1

Phase classification • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease

Efficacy and safety of the innovative monoclonal antibodies in adults with generalized myasthenia gravis: a Bayesian network analysis. (PubMed, Front Immunol) - "For efficacy outcomes, belimumab, efgartigimod, mezagitamab 600mg, and nipocalimab 60mg/kg were inferior to rozanolixzumab 7mg/kg (MD ranged from 2 to 3.69) and rozanolixzumab 10mg/kg (MD ranged from 2.04 to 3.72) in MG-ADL score, and rozanolixzumab had the highest rank probability (83%) according to the subjective surface under the curve ranking area (SUCRA). For QMG score, batoclimab 340mg (MD ranged from 4.32 to 8.52) and batoclimab 680mg (MD ranged from 4.11 to 9.31) were more effective than placebo and other monoclonal antibodies except for rozanolixzumab, with the highest SUCRA value (93% and 97% respectively)...Given the limitations inherent in indirect comparisons, further head-to-head and extensive observational studies are necessary to confirm our findings. https://inplasy.com/?s=202370112, identifier 202370112."

Journal • Review • CNS Disorders • Myasthenia Gravis

A Study Of TAK-981 Given With Monoclonal Antibodies (mAbs) In Adults With Relapsed or Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov) - P1b/2 | N=27 | Active, not recruiting | Sponsor: Takeda | Recruiting ➔ Active, not recruiting | N=81 ➔ 27 | Trial completion date: Aug 2026 ➔ Nov 2023 | Trial primary completion date: Feb 2025 ➔ Aug 2023

Combination therapy • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology

Novel therapeutics and future directions for refractory immune thrombocytopenia. (PubMed, Br J Haematol) - "Such agents include the neonatal Fc receptor antagonist efgartigimod, the Bruton tyrosine kinase inhibitor rilzabrutinib, the complement inhibitors sutimlimab and iptacopan and anti-CD38 monoclonal antibodies such as daratumumab and mezagitamab, among others. Each of these agents exploits therapeutic targets or other aspects of ITP pathophysiology currently not targeted by the existing approved agents (thrombopoietin receptor agonists and fostamatinib). This manuscript offers an in-depth review of the current available data for novel therapeutics in ITP presently undergoing phase 2 or 3 studies in patients with heavily pretreated or refractory ITP. It additionally highlights the future directions for drug development in refractory ITP, including discussion of innovative clinical trial designs, health-related quality of life as an indispensable clinical trial end-point and balancing potential toxicities of drugs with their potential benefits in a bleeding disorder in..."

Journal • Review • Hematological Disorders • Immunology • Thrombocytopenia • Thrombocytopenic Purpura

A Study to Evaluate Subcutaneous TAK-079 Added to Standard of Care Regimens in Participants With Newly Diagnosed Multiple Myeloma (NDMM) (clinicaltrials.gov) - P1b | N=50 | Active, not recruiting | Sponsor: Takeda | Trial completion date: Mar 2023 ➔ Feb 2024 | Trial primary completion date: Mar 2023 ➔ Feb 2024

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Solid Tumor • Transplantation

A Study of Mezagitamab in Adults With Primary Immunoglobulin A Nephropathy Receiving Stable Background Therapy (clinicaltrials.gov) - P1b | N=16 | Active, not recruiting | Sponsor: Takeda | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Nephrology • Renal Disease

A Study of TAK-079 in People With Generalized Myasthenia Gravis (clinicaltrials.gov) - P2 | N=36 | Completed | Sponsor: Takeda | Trial primary completion date: Mar 2022 ➔ Jul 2022

Trial primary completion date • CNS Disorders • Myasthenia Gravis

A Single Administration of the Cytolytic CD38 Antibody TAK-079 to Healthy Subjects: Tolerability, Pharmacokinetics and Pharmacodynamics (ASH 2018) - P1/2; "Pharmacodynamic effects included a transient, dose-dependent reduction in NK cells at doses ≥0.003 mg/kg IV, approximately 167-fold less than the lowest dose reported for NK cell reduction by daratumumab administered to RRMM patients IV (≥0.5 mg/kg1). References Blood Adv. 2017 Oct 24;1(23):2105-2114."

Clinical • PK/PD data • Biosimilar • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology