blisibimod (A-623) / Anthera Pharma - LARVOL DELTA

Anti-B-Cell-Activating Factor (BAFF) Therapy: A Novel Addition to Autoimmune Disease Management and Potential for Immunomodulatory Therapy in Warm Autoimmune Hemolytic Anemia. (PubMed, Biomedicines) - "Although rituximab is not specifically approved for the treatment of warm autoimmune hemolytic anemia (WAIHA), the First International Consensus Group recommends considering its use as part of the initial therapy for patients with severe disease and as a second-line therapy for primary WAIHA...This article reviews the role of BAFF in autoimmune disorders and the currently available literature on the use of BAFF-directed therapies in various immunologic disorders, including WAIHA. Collectively, the clinical data thus far shows robust potential for targeting BAFF in WAIHA therapy."

Immunomodulating • Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immunology

A narrative review of potential drug treatments for nephritis in children with IgA vasculitis (HSP). (PubMed, Clin Rheumatol) - "Novel drugs that may be considered for use in early nephritis include TRF-budesonide; B-cell inhibiting agents including belimumab, telitacicept, blisibimod, VIS649, and BION-1301; B-cell depleting agents such as rituximab, ofatumumab, and bortezomib; sparsentan; angiotensin converting enzyme inhibitors (ACE-Is); and complement pathway inhibitors including avacopan, iptacopan, and narsoplimab. • Novel treatments currently being trialled in IgA nephropathy may have benefit in IgA vasculitis due to the similarities in the underlying pathophysiology, such as TRF-budesonide, B-cell modulators, and complement inhibitors. • Further studies, including clinical trials of novel drugs, are urgently needed to improve the long-term outcomes for children with IgA vasculitis nephritis."

Journal • Review • Glomerulonephritis • IgA Nephropathy • Inflammation • Nephrology • Renal Disease • Vasculitis

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

Fine mapping of BnDM1-the gene regulating indeterminate inflorescence in Brassica napus. (PubMed, Theor Appl Genet) - "We found a 623-bp deletion in a region upstream of the KNU promoter in the mutant...This study presents as a new material for optimizing plant architecture and breeding novel canola varieties suitable for mechanized production. Moreover, our findings provide a theoretical basis for analyzing the molecular mechanisms underlying the formation of determinate inflorescence in B. napus."

Journal

Neutrophil-derived B-cell activating factor supports B/plasma-cell persistence and function in skin lesions in Hidradenitis suppurativa/Acne inversa (EHSF 2023) - "Medicamentous treatment options for HS remain very limited, with the anti-tumor necrosis factor-alpha antibody adalimumab as the only approved systemic treatment so far. In summary, neutrophil-derived BAFF seems to support B/plasma-cell persistence and function in HS lesions and might represent a new promising therapeutic target for HS. Since biological drugs that inhibit the BAFF activity are already approved (belimumab) or under clinical development for other medical indications (ianalumab, blisibimod), there is hope of a timely evaluation of these drugs in view of the reduction of the profound medical need that exists for HS."

IO biomarker • Acne Vulgaris • Dermatology • Hidradenitis Suppurativa • Inflammation • Oncology • Pain • BST2 • CD53 • CD8 • CXCR4 • PRKCB • TNFA • TNFRSF13B • TNFRSF13C • TNFRSF17 • TNFRSF1B

A heat shock protein protects against oxidative stress induced by lambda-cyhalothrin in the green peach aphid Myzus persicae. (PubMed, Pestic Biochem Physiol) - "MpHsp70 encoded a 623 amino acid protein putatively localized in the cytosol...Furthermore, knockdown of MpHsp70 by RNA interference resulted in increased susceptibility in apterous adults of M. persicae to LCT. These findings indicate that MpHsp70 plays an important role in defense against LCT-induced oxidative stress and insecticide susceptibility in M. persicae."

Journal

[VIRTUAL] Effects of B Cell Activating Factors/B Lymphocyte Stimulator Inhibitors Added to Standard of Care on Infection in Patients with Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (ACR-CONVERGENCE 2021) - " A systematic literature review was performed in PubMed, Embase, Cochrane Library databases from inception to Feb 2021 to identify randomized controlled trials (RCTs) of BAFFi/BLySi, including belimumab, tabalumab, blisibimod and atacicept. Adding BAFFi/BLySi to SoC in patients with SLE was not associated with increased risk of infection, serious infection, nor fatal infection."

Retrospective data • Review • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Genome assembly of a Mesoamerican derived variety of lima bean: a foundational cultivar in the Mid-Atlantic USA. (PubMed, G3 (Bethesda)) - "Our current study sought to sequence, assemble, and annotate a commercially available cultivar called Bridgeton, which could then serve as a reference genome, a basis of comparison to other Phaseolus taxa, and a resource for the identification of potential resistance genes. Combined efforts of sequencing, linkage, and comparative analysis resulted in a 623 Mb annotated assembly for lima bean, as well as a better understanding of an evolutionarily dynamic resistance locus in legumes."

Journal

[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

Modern, archaeological, and paleontological DNA analysis of a human-harvested marine gastropod (Strombus pugilis) from Caribbean Panama. (PubMed, Mol Ecol Resour) - "We first present reference assemblies for both a 623.7 Mbp nuclear genome and a 15.4 kbp mitochondrial genome for Strombus pugilis, the West Indian fighting conch...Reads also mapped to the S. pugilis mitochondrial genome for all but the paleontological shells, with consistent ratios of mitochondrial to nuclear mapped reads across sample types. Our methods can be applied to diverse archaeological sites to facilitate reconstructions of the long-term impacts of human behavior on mollusc evolutionary biology."

Journal

PHARMACOKINETICS AND CLINICAL EFFECTS OF A SINGLE ORAL DOSE OF TRAZODONE IN THE DOMESTIC GOAT (CAPRA HIRCUS) AS A MODEL FOR WILD RUMINANTS. (PubMed, J Zoo Wildl Med) - "This dose resulted in a 502% increase in time spent sleeping (P=0.0016) and a 623% increase in time spent lying down (P=0.01). Trazodone appears promising to decrease stress in exotic ruminant species. Further research is warranted to establish its efficacy in other ruminant species and clinical situations."

Clinical • Journal • PK/PD data • Mood Disorders • Psychiatry

Physiologic vasomotor symptoms are associated with verbal memory dysfunction in breast cancer survivors. (PubMed, Menopause) - "Independent of their effect on sleep, VMS may be a modifiable contributor to memory difficulties in women with breast cancer. These findings underscore the importance of objective measurement of VMS in cognitive studies. : Video Summary:http://links.lww.com/MENO/A623."

Journal • Breast Cancer • CNS Disorders • Oncology • Sleep Disorder • Solid Tumor

Physiologic vasomotor symptoms are associated with verbal memory dysfunction in breast cancer survivors. (PubMed, Menopause) - "Independent of their effect on sleep, VMS may be a modifiable contributor to memory difficulties in women with breast cancer. These findings underscore the importance of objective measurement of VMS in cognitive studies. : Video Summary:http://links.lww.com/MENO/A623."

Journal • Breast Cancer • CNS Disorders • Oncology • Solid Tumor

Anthera Pharmaceuticals reports 2013 fourth quarter and fiscal year financial results and operational update (PRNewswire) - Anticipated interim P3 data for CHABLIS-SC1 trial in mid 2014; "...the Company intends to submit a second lupus pivotal study (CHABLIS-SC2) to the US FDA in the first quarter of 2014."

Anticipated new P3 trial • Anticipated P3 data • Lupus

CHABLIS-SC1: A study of the efficacy and safety of subcutaneous blisibimod in subjects with systemic lupus erythematosus (clinicaltrials.gov) - P3, N=400; Sponsor: Anthera Pharmaceuticals; Not yet recruiting; Start date: Nov 2012 -> Feb 2013; N=700 -> 400

Enrollment change • Trial initiation date • Immunology • Lupus

Anthera Pharmaceuticals reports 2013 fourth quarter and fiscal year financial results and operational update (Anthera Pharmaceuticals Press Release) - P2/3, N=200; Sponsor: Anthera Pharmaceuticals; BRIGHT-SC (NCT02062684); "The Company anticipates the first 48 patients will complete eight weeks of treatment in the second half of 2014 upon which the Company plans to conduct an interim analysis to determine the effect of blisibimod on proteinuria. The Company anticipates feedback regarding its IgA development from the US FDA in the first quarter of 2014. Further discussions with the Japanese PMDA regarding development of blisibimod in Japan are planned for the second quarter of 2014."

Anticipated enrollment status • Anticipated FDA event • Anticipated Japanese regulatory • Anticipated P3 data: top line • Renal Disease

Anthera Pharmaceuticals announces completion of interim analysis from phase 3 trial with blisibimod for systemic lupus erythematosus (PRNewswire) - "Anthera Pharmaceuticals...today announced the successful completion of an interim analysis of its Phase 3 trial (CHABLIS-SC1) of blisibimod in patients with Systemic Lupus Erythematosus and that the study should continue to completion as planned...Enrollment in the trial is projected to conclude in mid-2015...Company modified the primary endpoint of CHABLIS-SC1 from SRI-8 response to SRI-6 response, which was previously a secondary endpoint of the study.  SRI-8 will remain a key secondary endpoint of the study."

Anticipated enrollment status • P3 data • Lupus

Effects of chronic treatment with subcutaneous blisibimod on renal and inflammation biomarkers in subjects with systemic lupus erythematosus in phase 2 PEARL-SC and open-label extension studies (EULAR 2014) - Presentation time: 13.06.2014, 11:45; Abstract #FRI0389; P2; N=547; PEARL-SC (NCT01162681); P2; N=600; OLE study (NCT01305746); Sponsor: Anthera Pharmaceuticals; "When compared with response in the patients randomized to placebo in PEARL-SC, there was a tendency toward increases in mean GFR in the patients receiving blisibimod at Week 24 in both renal subgroups with mean ΔGFR =1.4 and -3.0 mL/min [N=36,37], for blisibimod and placebo respectively, in the subgroup with baseline Pr/Cr ≥0.5."

Biomarker • P2 data • Lupus

Anthera Pharmaceuticals completes interim analysis of PEARL-SC clinical trial with blisibimod (Anthera Pharmaceuticals) - Anthera Pharmaceuticals announced the continuation of the P2b PEARL-SC clinical study following an interim analysis of all safety and efficacy data; The DSMB (Data Safety Monitoring Board) recommended the study proceed as planned without modification; Anticipated top-line efficacy data in Q2 2012

Anticipated P2b data • DSMB approval • Immunology • Lupus

Anthera Pharma: Q1 2015 Results (Anthera Pharmaceuticals) - Anticipated completion of enrollment in P3 CHABLIS-SC1 trial for systemic lupus erythematosus in 2015; Anticipated topline data from P3 CHABLIS-SC1 trial for systemic lupus erythematosus in H2 2016 

Anticipated enrollment status • Anticipated P3 data: top line • Lupus

Anthera Pharmaceuticals: Corporate Update (Anthera Pharmaceuticals) - Anticipated enrollment completion of P3 Chablis 7.5 trial (NCT02514967) for systemic lupus erythematosus in Q4 2017; Anticipated topline data from P3 Chablis 7.5 trial for systemic lupus erythematosus in Q1 2019 

Anticipated enrollment status • Anticipated P3 data: top line • Lupus

Blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus (ACR/ARHP 2012) - Presentation time: Tuesday, November 13; 9:00 AM - 6:00 PM; P2, N=547; NCT01162681; "The primary endpoint of this study was not met primarily due to the lack of efficacy in the two lowest dose groups. However, SRI-5 responder rates were higher in subjects receiving blisibimod 200mg QW compared with pooled placebo, from Week 16 (DSRI‑5 for blisibimod-placebo=8%, p= 0.14), through Week 24 (DSRI‑5=8.2%, p=0.15), reaching statistical significance at Week 20 (DSRI‑5=13.4%, p = 0.02)"

P2 data • Immunology • Lupus

CHABLIS7.5: A Study of the Efficacy and Safety of Subcutaneous Blisibimod in Subjects With Systemic Lupus Erythematosus With or Without Nephritis (clinicaltrials.gov) - P3; N=350; Recruiting; Sponsor: Anthera Pharmaceuticals; Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar • Lupus

Blisibimod: Anticipated expiry of patents in US in May 2022, March 2023 and November 2023 (Anthera Pharmaceuticals) - Annual Report 2016: Anticipated term extension of patents in US until May 2027, March 2028 or November 2028; Anticipated expiry of patents in Europe in May 2022; Anticipated patent term extension in EU until May 2027; Anticipated expiry of new chemical entity patent in US in 2027/2028; Anticipated expiry of new chemical entity patents in EU in 2027

Patent expiry • Lupus