- |||||||||| Review, Journal, IO biomarker: Current status of BAFF targeting immunotherapy in B-cell neoplasm. (Pubmed Central) - Oct 26, 2024
Belimumab, an anti-BAFF monoclonal antibody, is being investigated in combination with rituximab/venetoclax for CLL...The review emphasizes the importance of understanding the roles of BAFF and its receptors in the microenvironment of hematologic malignancies. Targeting BAFF and its receptors presents potential therapeutic avenues, and ongoing clinical trials provide valuable insights.
- |||||||||| tabalumab (LY2127399) / Eli Lilly
Journal: Analysis of transcriptomic features reveals molecular endotypes of SLE with clinical implications. (Pubmed Central) - Oct 22, 2023 Transcriptomic profiling and ML reproducibly separated lupus patients into molecular endotypes with significant differences in clinical features, outcomes, and responsiveness to therapy. Our classification approach using a composite scoring system based on underlying molecular abnormalities has both staging and prognostic relevance.
- |||||||||| tabalumab (LY2127399) / Eli Lilly
Validation of a Transcriptomic-Based Machine Learning Model to Establish the Endotype of SLE Patients (Poster Hall; in person) - Sep 23, 2023 - Abstract #ACRConvergence2023ACR_Convergence_2150; P=N/A Patients in the endotypes with the least immunologic activity did not have proliferative nephritis and also experienced no lupus flares during the subsequent six months. Endotyping SLE patients based on gene expression profiles can provide important prognostic information and provide novel molecular insights in support of personalized management.
- |||||||||| Review, Journal: Advances in natural products and antibody drugs for SLE: new therapeutic ideas. (Pubmed Central) - Jul 26, 2023
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.
- |||||||||| Benlysta (belimumab) / GSK, tabalumab (LY2127399) / Eli Lilly
Journal: Distinct binding mode of BAFF antagonist antibodies belimumab and tabalumab, analyzed by computer simulation. (Pubmed Central) - Sep 7, 2022 More importantly, belimumab could bind to L83 of BAFF and produce steric hindrance with the adjacent BAFF trimers, while tabalumab could not. Therefore, our results indicated that belimumab has a better clinical outcome compared with tabalumab mainly because belimumab could bind to L83 of BAFF and interfere the formation of a BAFF 60-mer, besides mediating inhibition of the interaction of BAFF with its receptors.
- |||||||||| Zinbryta (daclizumab) / Biogen, AbbVie, tabalumab (LY2127399) / Eli Lilly
Review, Journal: What Have Failed, Interrupted, and Withdrawn Antibody Therapies in Multiple Sclerosis Taught Us? (Pubmed Central) - Jul 23, 2022 mAbs that have been proven to be safe in other autoimmune conditions, will not have the same safety profile in MS due to immunopathogenetic differences in these diseases (e.g., daclizumab)...Memory B cells are central players in MS immunopathogenesis (e.g., tabalumab)...The success of trials on remyelination-promoting therapies mainly depends on the sufficient high dose of mAb, the optimal readout for 'proof of concept', time of treatment initiation, and appropriate selection of patients. Failed strategies are highly important to better understand assumed immunopathophysiological mechanisms and optimizing future trial designs.
- |||||||||| Benlysta (belimumab) / GSK, atacicept (VT-001) / Vera Therap, tabalumab (LY2127399) / Eli Lilly
Journal: Advances of using antibody against B cell activating factor for treatment of autoimmune diseases (Pubmed Central) - Apr 7, 2022 In connection to the treatment of the above three diseases, this review discusses the clinical trials and application status of three BAFF-targeting antibody drugs, including Belimumab, Tabalumab and Atacicept. Finally, this review proposes new strategies that targeting the BAFF pathway to provide a new treatment for autoimmune diseases.
- |||||||||| Orencia (abatacept) / BMS, Arzerra (ofatumumab) / Novartis, Genmab
Journal: Current understanding and unknown aspects of the treatment of granulomatosis with polyangiitis (Wegener's granulomatosis): Opportunities for future studies. (Pubmed Central) - Oct 8, 2021 Renal involvement, older age, the presence of baseline organ damage, delayed-diagnosis of disease, rising in creatinine level, and higher neutrophil/lymphocyte ratio is associated with poor outcomes. Optimum doses of medications, prediction of treatment response and disease relapse, explaining lack of response in some patients, treating children with GPA, and management of GPA during the pregnancy are controversial issues, which need further studies.
- |||||||||| Review, Journal: Emerging B-Cell Therapies in Systemic Lupus Erythematosus. (Pubmed Central) - Jan 26, 2021
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.
- |||||||||| atacicept (TACI-Ig) / EMD Serono, tabalumab (LY2127399) / Eli Lilly
Journal: Failed B cell survival factor trials support the importance of memory B cells in multiple sclerosis. (Pubmed Central) - Dec 18, 2020 P2 Although other interpretations are possible, this data further supports the hypothesis that memory B cells may be of central importance in relapsing MS, as they are the major CD20+ B cell subset expressing APRIL receptors. It also suggests that quantitative and/or qualitative differences in B cell responses or other factors, such as immune-regulatory effects-associated with APRIL, may be important in determining whether MS reactivates following neutralization of peripheral B cell maturation and survival factors.
- |||||||||| Retrospective data, Review, Journal: Late-Stage Failures of Monoclonal Antibody Drugs: A Retrospective Case Study Analysis. (Pubmed Central) - Oct 30, 2020
It also suggests that quantitative and/or qualitative differences in B cell responses or other factors, such as immune-regulatory effects-associated with APRIL, may be important in determining whether MS reactivates following neutralization of peripheral B cell maturation and survival factors. By learning from previous mistakes and adhering to the principles and recommendations provided, it is possible to avoid these common pitfalls, increasing the likelihood of success in phase III clinical trials, and thus securing regulatory approval.
- |||||||||| Actemra IV (tocilizumab) / Roche, JW Pharma, Darzalex IV (daratumumab) / J&J
[VIRTUAL] Peak DSA Levels Pre-Transplant but Not at Transplant Predict Graft Survival (Virtual) - May 29, 2020 - Abstract #ATC2020ATC_509; Under pharmacologic influence, the magnitude and change in DSA levels between sensitization and KTx may be a better prognostic tool than DSA levels at KTx. Given differences in regimens and timelines in this cohort, these findings deserve further investigation.
- |||||||||| tabalumab (LY2127399) / Eli Lilly
Journal: A Bayesian gene network reveals insight into the JAK-STAT pathway in systemic lupus erythematosus. (Pubmed Central) - Mar 29, 2020 In order to further advance our understanding of the pathogenesis of SLE, we used a novel Bayesian network algorithm to hybridize knowledge- and data-driven methods, and then applied the algorithm to build an SLE gene network using transcriptomic data from 1,760 SLE patients' RNA from the two tabalumab Phase III trials (ILLUMINATE-I & -II), the largest SLE RNA dataset to date...Additionally, we showed that other genes, such as IRF1, IRF7, PDIA4, FAM72C, TNFSF10, DHX58, SIGLEC1, and PML, may be also important in SLE and serve as potential therapeutic targets for SLE. In summary, using a hybridized network construction approach, we systematically investigated gene-gene interactions based on their transcriptomic profiles, prioritized genes based on their importance in the network structure, and revealed new insights into SLE activity.
- |||||||||| tabalumab (LY2127399) / Eli Lilly
Biomarker, Enrollment change, Trial termination, Biopsy: A Study of LY2127399 in Rheumatoid Arthritis (clinicaltrials.gov) - Jun 3, 2018 P2, N=2, Terminated, Completed --> Terminated; Insufficient efficacy observed in study BCDM(NCT01198002) and BCDV(NCT01202773) N=36 --> 2 | Completed --> Terminated; Insufficient efficacy observed in study BCDM(NCT01198002) and BCDV(NCT01202773).
- |||||||||| tabalumab (LY2127399) / Eli Lilly
Journal: The impact of tabalumab on the kidney in systemic lupus erythematosus: results from two phase 3 randomized, clinical trials. (Pubmed Central) - May 20, 2017 P3 Compared to placebo, tabalumab did not significantly affect the serum creatinine concentration, glomerular filtration rate, urine protein/creatinine ratio, or renal flare rates over 1 year in intent-to-treat or intent-to-treat plus urine protein/creatinine ratio patients. There were no significant renal safety signals.ClinicalTrials.gov identifiers: NCT01205438 and NCT01196091 Lupus (2016) 25, 1597-1601.
- |||||||||| tabalumab (LY2127399) / Eli Lilly
Trial completion, Trial primary completion date, Combination therapy: A Phase 1 Safety Study of LY2127399 in Combination With Bortezomib (clinicaltrials.gov) - May 26, 2015 P1, N=48, Completed, Trial primary completion date: May 2014 --> Jan 2013 Active, not recruiting --> Completed | Trial primary completion date: Dec 2012 --> May 2014
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