Epratucyn (epratuzumab) / Gilead - LARVOL DELTA

TRANSPLANT RELATED HEPATIC DYSFUNCTION AND MORTALITY AFTER MATCHED RELATED DONOR STEM CELL TRANSPLANT IN CHILDREN WITH ACUTE LEUKEMIA PREVIOUSLY TREATED WITH IMMUNOTHERAPY (EBMT 2025) - "Twenty-six patients (29%) received one or more immunotherapies prior to SCT: blinatumomab (16), gemtuzumab (3), inotuzumab (3), epratuzumab (2), daratumumab (1), and CAR-T (6). Immunotherapy may be associated with increased risk of hepatic dysfunction following SCT, which is independently associated with NRM. This may result from liver injury related to receipt of immunotherapy or more lines of therapy prior to transplant than in the pre-immunotherapy era. This association requires validation from independent studies."

Clinical • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • CNS Disorders • Graft versus Host Disease • Hematological Malignancies • Hepatology • Immunology • Leukemia • Liver Failure • Oncology • Pediatrics • Transplantation

TRANSPLANT RELATED HEPATIC DYSFUNCTION AND MORTALITY AFTER MATCHED RELATED DONOR STEM CELL TRANSPLANT IN CHILDREN WITH ACUTE LEUKEMIA PREVIOUSLY TREATED WITH IMMUNOTHERAPY (EBMT 2025) - "Twenty-six patients (29%) received one or more immunotherapies prior to SCT: blinatumomab (16), gemtuzumab (3), inotuzumab (3), epratuzumab (2), daratumumab (1), and CAR-T (6). Immunotherapy may be associated with increased risk of hepatic dysfunction following SCT, which is independently associated with NRM. This may result from liver injury related to receipt of immunotherapy or more lines of therapy prior to transplant than in the pre-immunotherapy era. This association requires validation from independent studies."

Clinical • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • CNS Disorders • Graft versus Host Disease • Hematological Malignancies • Hepatology • Immunology • Leukemia • Liver Failure • Oncology • Pediatrics • Transplantation

Asciminib Maintains Antibody-Dependent Cellular Cytotoxicity against Leukemic Blasts. (PubMed, Cancers (Basel)) - P1/2, P2 | "The introduction of rituximab has improved the outcomes in CD20 positive cases. Other monoclonal antibodies, such as tafasitamab (anti-CD19), obinutuzumab (anti-CD20) and epratuzumab (anti-CD22) have been tested in trials (NCT05366218, NCT04920968, NCT00098839)...In contrast to ATP site inhibitors such as dasatinib and ponatinib, the novel first-in-class selective allosteric ABL myristoyl pocket (STAMP) inhibitor asciminib did not significantly impact ADCC in our settings. Our results suggest that asciminib should be considered in clinical trials."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • ABL1 • BCR

Pipeline Moves: Approval prospects for ALL candidate rise after Phase III completion (Clinical Trials Arena) - "This week on Pipeline Moves, we kick off by looking at the completion of a Phase III investigator-led trial of Gilead Sciences’s epratuzumab in acute lymphocytic leukaemia....Gilead Sciences’s saw its likelihood of approval (LoA) in acute lymphocytic leukaemia (ALL) increase after an investigator-led Phase III trial was completed....The Phase III trial’s (NCT01802814) status was updated from ongoing to completed on ClinicalTrials.gov on 12 February with GlobalData evaluating the product on the same day."

Trial completion • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

IntReALL SR 2010: International Study for Treatment of Standard Risk Childhood Relapsed ALL 2010 (clinicaltrials.gov) - P3 | N=700 | Completed | Sponsor: Charite University, Berlin, Germany | Active, not recruiting ➔ Completed

Trial completion • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD22

Model-based meta-analysis using latent variable modeling to set benchmarks for new treatments of systemic lupus erythematosus. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Continuous dose-effect relationships using a maximum effect model were included for anifrolumab, belimumab, CC-220 (iberdomide), epratuzumab, lulizumab pegol, and sifalimumab, whereas the remaining treatments were modeled as discrete dose effects. The final MBMA model was then used to benchmark these compounds with respect to the maximal efficacy on the latent variable compared to the placebo. This MBMA illustrates the application of latent variable models in understanding the trajectories of composite end points in chronic diseases and should enable model-informed development of new investigational agents in SLE."

Journal • Retrospective data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Disease Course and Complement as Predictors of Response to Standard of Care Plus Placebo in Patients with SLE: A Post Hoc Analysis of Dapirolizumab Pegol and Epratuzumab Clinical Trial Data (ACR Convergence 2023) - P2, P3 | "In both EMBODY 1/2 and RISE, acute flare predicted SOC+PBO response. In RISE, normal complement levels also predicted SOC+PBO response; low complement has been described as a predictor of increased treatment effect in previous studies. 5 Recent medical history of pts may have to be considered when defining SLE study populations."

Clinical • Retrospective data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD40LG

Advances in natural products and antibody drugs for SLE: new therapeutic ideas. (PubMed, Front Pharmacol) - "This review discusses the current experience including B-cell targeted drugs (belimumab, tabalumab, blisibimod, atacicept, rituximab, ofatumumab, ocrelizumab, obexelimab, and epratuzumab), T-cell targeted drugs (abatacept, dapirolizumab, and inhibitor of syk and CaMKIV), cytokines targeted drugs (anifrolumab and sifalimumab), and natural products (curcumin, oleuropein, punicalagin, sulforaphane, icariin, apigenin, and resveratrol). The aim of this paper is to combine the existing in vitro and in vivo models and clinical research results to summarize the efficacy and mechanism of natural drugs and targeted drugs in SLE for the reference and consideration of researchers."

Journal • Review • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • SYK

Efficacy of Monoclonal Antibodies in Adult Acute Lymphoblastic Leukemia: A Systematic Review (TCT-ASTCT-CIBMTR 2022) - "We found clinical data on the CD 22 antibodies inotuzumab (INO) and epratuzumab (EMAB), CD 20 antibodies rituximab (RIX) and ofatumumab (OFM), CD 19 antibody blinatumomab (BLN), and CD 52 antibody alemtuzumab (ALZ). Monoclonal antibodies targeting various cell surface receptors show promising responses in the treatment of adult B-ALL. Most antibodies are well tolerated and have shown superior efficacy compared to the standard of care regimens. These antibodies have an acceptable safety profile with fewer systemic effects."

Clinical • Review • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia

[VIRTUAL] Analysis of Adct-602 Pre-Clinical Activity in B-Cell Lymphoma Models and Identification of Potential Biomarkers for Its Activity (ASH 2020) - P1/2 | "ADCT-602 is an antibody drug conjugate (ADC) composed of Emab-C220, an engineered version of the anti-CD22 humanized IgG1 antibody epratuzumab, site-specifically conjugated to SG3249, which includes the DNA minor groove crosslinking pyrrolobenzodiazepine (PBD) dimer SG3199 linked to the antibody via a protease-cleavable linker (Zammarchi et al, ASH 2016). Expression signatures and other features (MZL or DHT DLBCL histology), but not the expression levels of its target, were associated with different sensitivity to the ADC. Our data supports the clinical evaluation of ADCT-602 in patients with B-cell lymphoma in addition to B-ALL."

IO Biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukaemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Inflammation • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • BCL2 • IL2 • MYC • STAT5 • TGFB1 • TP53

ALL-REZ BFM 2002 Is Associated with Improved Outcome as Compared to ALL-R3 Strategy in Children with Standard Risk Isolated CNS Relapse of Acute Lymphoblastic Leukemia, while Maintaining Comparable Efficacy in Patients with Bone Marrow Relapse. Results of the Multi-National, Multi-Center Trial IntReALL SR 2010 (ASH 2022) - "During consolidation, patients were randomized to receive the CD22-directed monoclonal antibody epratuzumab in addition to backbone chemotherapy... Both arm A and B were effective in this large multi-national trial. EFS and OS probabilities compare favorably to results recently published by other cooperative groups. In particular, the outcome of patients with early IEM relapse or with late BM relapse and MRD poor response is encouraging confirming the benefit of allo HSCT in these subgroups."

Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • CD22

B cell depletion and inhibition in systemic lupus erythematosus. (PubMed, Expert Rev Clin Immunol) - "However, after more than two decades of research and over 40 randomized clinical trials, only one such therapy, belimumab, has been approved for use in SLE...Despite a lack of supporting phase III evidence, rituximab is used off-label in SLE...Successful phase II trials have recently been reported for obinutuzumab and telitacicept with larger confirmatory trials currently underway. Refinements in pharmaceutical mechanisms of action, trial design, and patient selection have resulted in recent preliminary successes, offering renewed optimism for B-cell targeted therapeutics in SLE management."

Clinical • Journal • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

Clinical trials in systemic lupus erythematosus: the dilemma-Why have phase III trials failed to confirm the promising results of phase II trials? (PubMed, Ann Rheum Dis) - "Thus, trials with many drugs against different targets, such as CD22, IL-12 and IL-23 or tyrosine kinases, have been carried out in recent years.A frustrating feature of some of the biologic drugs used to treat SLE has been the reporting of successful phase II trials followed by failures of the phase III trials.In this review, we will focus on phase II and III trials carried out with epratuzumab (anti CD22), baricitinib (Janus kinases inhibitor), rigerimod (P140 peptide) and ustekinumab (IL-12 and IL-23 inhibitor) and consider the reasons for their ultimate failure to 'make the grade'. Likewise, we will try to explain the possible reasons that can influence why good results may be obtained in phase II trials and lead to undue optimism."

Journal • P2 data • P3 data • Review • Glomerulonephritis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Rheumatology • Systemic Lupus Erythematosus • IL12A • IL23A

Immunotherapy in indolent Non-Hodgkin's Lymphoma. (PubMed, Leuk Res Rep) - "Other than that, a resistance mechanism to rituximab emerged by inducing a failure in the apoptosis mechanism...Here came the development of 90Y-ibritumomab tiuxetan and 131I-tositumomab. After it, humanized anti-CD20 emerged ofatumumab, IMMU106 (veltuzumab) in 2005, and ocrelizumab which are considered as second generation anti-CD20 and 3 generation anti-CD20 include AME-133v (ocaratuzumab), PRO131921 and GA101 (obinutuzumab). Also multiple other agents emerged targeting different surface cell antigens like CD52 (alemtuzumab), CD22 (unconjugated epratuzumab and calicheamicin conjugated CMC-544 [inotuzumab ozogamicin]), CD80 (galiximab), CD2 (MEDI-507 [siplizumab]), CD30 (SGN-30 and MDX-060 [iratumumab], Brentuximab vedotin), CD40 (SGN-40), and CD79b (Polatuzumab). Other agents include MAB targeting T-Cells like mogamulizumab, Denileukin Diftitox and BiTEs or bispecific T cell engagers like Mosunetuzumab, Glofitamab, and Epcoritamab...Another important aspect in..."

Journal • Allergy • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Immune Modulation • Indolent Lymphoma • Inflammation • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • CD22 • CD40 • CD52 • CD79B • TNFRSF8

Direct CNS administration of rituximab and epratuzumab in a pediatric patient with relapsed refractory CNS B-cell acute lymphoblastic leukemia. (PubMed, Pediatr Blood Cancer) - "Systemic monoclonal antibody therapy has shown recent promise in patients with relapsed acute lymphoblastic leukemia, however its effect on CNS disease in this population is not well established. We describe a case of multiply relapsed and refractory CNS leukemia in an adolescent patient who responded to the intra-CNS delivery of rituximab (anti-CD20) and epratuzumab (anti-CD22) therapy, demonstrating the practical use and potential efficacy of a novel route of monoclonal antibody administration in difficult-to-treat CNS leukemia."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics

[VIRTUAL] Efficacy of Anifrolumab in Patients with SLE Previously Treated with Biologics: Post Hoc Analysis of Data from 2 Phase 3 Trials (ACR-CONVERGENCE 2021) - P3 | "Efficacy measures included BILAG–based Combined Lupus Assessment (BICLA) response at Week (W) 52; SLE Responder Index of ≥4 (SRI[4]) response at W52; sustained oral glucocorticoid (GC) taper (≤7.5 mg/day prednisone equivalent, W40−52, if ≥10 mg/day at baseline); and annualized flare rate through W52...Most previous biologic use was with belimumab (n=70), epratuzumab (n=49), tabalumab (n=18), or rituximab (n=14)... Regardless of whether patients with SLE had previously received biologics, anifrolumab 300 mg provided clinically meaningful benefit over placebo across efficacy endpoints and was generally well tolerated. 1. Furie RA."

Clinical • P3 data • Retrospective data • Herpes Zoster • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Varicella Zoster

Distinct patterns of disease activity over time in patients with active SLE revealed using latent class trajectory models. (PubMed, Arthritis Res Ther) - "Longitudinal nBILAG scores reveal different trajectories of disease activity and may offer advantages over fixed endpoints. Corticosteroid use however remains an important confounder in lupus trials and can influence early response. Changes in disease activity and steroid dose early in the trial were associated with the overall disease activity trajectory, supporting the feasibility of performing adaptive trial designs in SLE."

Clinical • Journal • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD22

Targeting CD22 for the Treatment of B-Cell Malignancies. (PubMed, Immunotargets Ther) - "A variety of therapies targeting CD22 have been developed, including monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, chimeric antigen receptor T cells, and bispecific antibodies. Here, we review the biology of CD22 and key therapies targeting CD22 in lymphoid malignancies."

Journal • Review • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Oncology • CD19 • CD20 • CD22

[VIRTUAL] Efficacy of Biological Agents for the Management of Systemic Lupus Erythematosus: A Systematic Review and Network Meta-Analysis (CRA-AHPA 2021) - "These 20 RCTs investigated the following biologics: belimumab, anifrolumab, ustekinumab, atacicept, baricitinib, blisibimod, epratuzumab, IL-2, lupuzor, PF-04236921, rontalizumab, sifalimumab, and tabalumab... The NMA identified that belimumab, anifrolumab and ustekinumab demonstrated greater response in comparison to placebo, when measured using SRI. This systematic review identified that there was heterogeneity in the outcome measures and endpoints used. In the future, the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be applied to rate the quality of the evidence, and to gain insight into methodological pitfalls that could have negatively altered the results of RCTs."

Retrospective data • Review • Complement-mediated Rare Disorders • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus • IL2

Emerging B-Cell Therapies in Systemic Lupus Erythematosus. (PubMed, Ther Clin Risk Manag) - "This review discusses the current experience with B-cell-targeted therapies, including those targeting B-cell-surface antigens (rituximab, ocrelizumab, ofatumumab, obinutuzumab, obexelimab, epratuzumab, daratumumab), B-cell survival factors (belimumab, tabalumab, atacicept, blisibimod), or B-cell intracellular functions (ibrutinib, fenebrutinib, proteasome inhibitors), for the management of SLE. It focuses on ongoing clinical trials and real-world post-marketing use, where available, including their safety profiles, and concludes with our recommendations for B-cell-centric approaches to the management of SLE."

Journal • Review • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

B cell modulation strategies in the improvement of transplantation outcomes. (PubMed, Mol Immunol) - "Nowadays, several monoclonal antibodies (mAb) are available for B cell modulation that are routinely used in transplant recipients, among which rituximab (anti-CD20 mAb) act in eliminating B cells. However, there are some other monoclonal antibodies, such as epratuzumab and Inotuzumab ozogamicin (IO), which exert anti-CD22 activity, resulting in disruption of B cell functions and induction of tolerance in autoimmune disease or B cell malignancies; that notwithstanding, these mAbs have not yet been tried in transplantation. In this review, we focus on different methods for modulating the activity of B cells as well as induction of Breg cells, aiming to prevent the allograft rejection."

Journal • Review • Antibody-mediated Rejection • Immunology • Oncology • Transplantation

International Study for Treatment of Standard Risk Childhood Relapsed ALL 2010 (clinicaltrials.gov) - P3; N=700; Active, not recruiting; Sponsor: Charite University, Berlin, Germany; Recruiting ➔ Active, not recruiting; N=1242 ➔ 700; Trial completion date: Nov 2023 ➔ Jul 2023

Enrollment change • Enrollment closed • Trial completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Therapeutic interventions of tissue specific autoimmune onset in systemic lupus erythematosus. (PubMed, Mini Rev Med Chem) - "Keeping a close eye on the mechanisms of disease onset, a comprehensive view is provided on recent therapy of systemic lupus erythematosus."

Journal • Biosimilar • Immunology • Lupus

Two year follow-up on biologics use in 13 centers- data from the international registry for biologics in systemic lupus erythematosus (ACR-ARHP 2013) - Presentation time: Monday, October 28, 2013; 8:30 am - 4:00 pm; Abstract #1607; P=NA, N=455; “At two-year follow-up (n=120), SLE disease activity (SLEDAI) and corticosteroid (CS) dose were significantly lower versus baseline (SLEDAI: 9.4±5.3 to 3.1±2.5; CS dose: 10.7±13.9 to 4.8±5.9 mg; mean±SD paired analyses, p<0.0001 for both comparisons). SLICC damage-index remained unchanged.”

Retrospective data • Biosimilar • Lupus

Novel antibody therapy in acute lymphoblastic leukemia (Curr Hematol Malig Rep) - "The anti-CD20 antibody, rituximab, anti CD22 antibody, epratuzumab, anti-CD22 antibody-drug conjugate, Inotuzumab ozogamicin, the bi-specific T-cell engager (BiTE) antibody, Blinatumomab, and chimeric receptor antigen (CAR) therapy are among the emerging agents that have demonstrated the potential to improve response rate and decrease toxicity when used alone or in combination with chemotherapy."

Review • Acute Lymphocytic Leukemia • Biosimilar • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology