atacicept (VT-001) / EMD Serono, Vera Therap - LARVOL DELTA

ORIGIN Extend: A Long-Term Extension Study of Atacicept in IgA Nephropathy (ERA 2025) - No abstract available

Glomerulonephritis • IgA Nephropathy • Renal Disease

ORIGIN 3 Study Design: A Global, Randomized, Controlled, Phase 3 Study of Atacicept in IgA Nephropathy (ERA 2025) - No abstract available

Clinical • P3 data • Glomerulonephritis • IgA Nephropathy • Renal Disease

ORIGIN 2b: Changes in Gd-IgA1 and eGFR After Discontinuation of Atacicept Treatment in IgA Nephropathy (ERA 2025) - No abstract available

Glomerulonephritis • IgA Nephropathy • Renal Disease

ORIGIN: Atacicept in Subjects With IgA Nephropathy (clinicaltrials.gov) - P3 | N=376 | Active, not recruiting | Sponsor: Vera Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Glomerulonephritis • IgA Nephropathy • Renal Disease

ORIGIN EXTEND: A Rollover Study to Evaluate the Long-Term Safety and Efficacy of Atacicept (clinicaltrials.gov) - P2 | N=476 | Enrolling by invitation | Sponsor: Vera Therapeutics, Inc. | Recruiting ➔ Enrolling by invitation

Enrollment status • Glomerulonephritis • IgA Nephropathy • Renal Disease • CST3

Vera Therapeutics Completes Full Enrollment in Pivotal ORIGIN Phase 3 Trial for Atacicept in IgAN (GlobeNewswire) - "Vera Therapeutics, Inc...announced that it has completed full enrollment in the pivotal ORIGIN Phase 3 trial of atacicept in patients with IgA Nephropathy (IgAN)....The ORIGIN 3 trial (NCT04716231) is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 trial evaluating the safety and efficacy of atacicept in patients with IgAN who have persistent proteinuria and remain at high risk of disease progression. Participants are randomized 1:1 to at-home self-administered once-weekly subcutaneous injections of atacicept 150 mg or placebo for a 104-week double-blind period, followed by a 52-week open-label extension."

Enrollment closed • IgA Nephropathy

Vera Therapeutics Provides Business Update and Reports Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "Planned updates from the ongoing pivotal ORIGIN 3 trial: Anticipate full enrollment in 2Q 2025; On track to announce the primary endpoint result in 2Q 2025; Plan to submit a BLA to the U.S. FDA in 2H 2025 for atacicept in IgAN for accelerated approval assuming supportive data; and would expect a PDUFA date and commercial launch in 2026; QM dose finding study initiating in 2025 to evaluate extended dosing; Plan to initiate the PIONEER trial in 2025, which would evaluate atacicept in expanded IgAN populations and anti-PLA2R positive PMN and anti-nephrin positive FSGS and MCD."

Enrollment status • FDA approval • FDA filing • Launch US • New trial • P3 data: top line • IgA Nephropathy

Long-term Results from the ORIGIN Phase 2b Study of Atacicept for the Treatment of IgAN (ISN-WCN 2025) - "Baba M. PLoS One 2015. This abstract was also submitted for the ASN Kidney Week 2024 congress."

P2b data • Glomerulonephritis • IgA Nephropathy

ORIGIN Extend: A Long-Term Extension Study of Atacicept in IgAN (ISN-WCN 2025) - "Conclusions The ORIGIN Extend study will enable continued access to atacicept for participants of a parent study and provide extended long-term data on the disease-modifying potential of atacicept in IgAN. This abstract was also presented at the ASN Kidney Week 2024 congress."

Glomerulonephritis • IgA Nephropathy

TACI Ig Fusion Protein Inhibits TLR4/MyD88/NF-κB Pathway Alleviates Renal Injury in IgA Nephropathy Rats. (PubMed, Iran J Kidney Dis) - "TACI-Ig mitigates renal injury in IgAN rats by reducing inflammatory infiltration and IgA deposition and suppressing the pathway of TLR4/MyD88/NF-κB, offering data for developing effective treatments for IgAN."

Journal • Preclinical • Fibrosis • Glomerulonephritis • IgA Nephropathy • Immunology • Renal Disease • MYD88 • TLR4

ORIGIN EXTEND: A Rollover Study to Evaluate the Long-Term Safety and Efficacy of Atacicept (clinicaltrials.gov) - P2 | N=476 | Recruiting | Sponsor: Vera Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Glomerulonephritis • IgA Nephropathy • Renal Disease

Imbalanced Expression of TACI Isoforms Regulated By TNFRSF13B Variants Promotes the Progression of Epstein-Barr Virus-Associated Lymphoproliferative Diseases (ASH 2024) - "For patients who carry the gain-of-function germline mutations of TNFRSF13B, the inhibitory TACI-Ig or the TACI ligands BAFF and APRIL may efficiently prevent the serious progression of their EBV infection. Screening for possibly pathogenic variants, especially in the TNF-TNFR superfamily genes in EBV-LPD patients is necessary and valuable for understanding the pathogenesis of EBV-LPDs and optimizing the therapeutic regimen."

Epstein-Barr Virus Infections • Infectious Disease • Oncology • TNFA • TNFRSF13B • TUSC3 • UNC13D

Comparative Efficacy and Safety of New Therapies for IgA Nephropathy: A Systematic Review and Network Meta-Analysis (KIDNEY WEEK 2024) - "This systematic review and network meta-analysis indicate Mycophenolate and Telitacicept are most effective in reducing UPCR and improving eGFR, suggesting these as preferable treatments for IgAN patients."

Retrospective data • Review • Glomerulonephritis • IgA Nephropathy • Renal Disease

ORIGIN EXTEND: A Rollover Study to Evaluate the Long-Term Safety and Efficacy of Atacicept (clinicaltrials.gov) - P2 | N=476 | Not yet recruiting | Sponsor: Vera Therapeutics, Inc.

New P2 trial • Glomerulonephritis • IgA Nephropathy • Renal Disease

Long-Term Results from the ORIGIN Phase 2b Study of Atacicept for the Treatment of IgA Nephropathy (IgAN) (KIDNEY WEEK 2024) - "Gd-IgA1, hematuria, and UPCR reductions with eGFR stabilization through 96 weeks demonstrate that atacicept offers a potentially safe, long-term, disease-modifying treatment for IgAN. Specifically, the conversion of an eGFR profile in patients with IgAN from one of steady decline to one representative of the general population without kidney disease1 supports the potential of atacicept to decrease the high lifetime risk of kidney failure in patients with IgAN."

Late-breaking abstract • P2b data • Glomerulonephritis • IgA Nephropathy • Renal Disease

ORIGIN Extend: A Rollover Extension Study to Continue to Evaluate the Long-Term Safety and Efficacy of Atacicept (KIDNEY WEEK 2024) - "The ORIGIN Extend study will enable continued access for participants of a parent study and provide extended long-term data for atacicept in IgAN.1Kwon CS. J Health Econ Outcomes Res 20212Pitcher D. Clin J Am Soc Nephrol 20233Lafayette R. Nephrol Dial Transplant 2024; abstr 812"

Clinical • Glomerulonephritis • IgA Nephropathy • Nephrology • Renal Disease

ORIGIN 3: Pivotal Ph3 Study Evaluating Effect of Atacicept vs. Placebo on Proteinuria and Kidney Function Preservation in IgAN (KIDNEY WEEK 2024) - "The key secondary endpoint is eGFR change from baseline at 104wk.This pivotal Ph3 study will further evaluate atacicept's disease-modifying potential as a treatment for IgAN.1Kwon CS. J Health Econ Outcomes Res 20212Pitcher D. Clin J Am Soc Nephrol 20233Lafayette R. Nephrol Dial Transplant 2024; abstr 812"

Clinical • P3 data • Glomerulonephritis • IgA Nephropathy • Lupus Nephritis • Renal Disease

Complement and B Cell Modifying Pipeline to Address Unmet Needs in IgA Nephropathy (IgAN) (KIDNEY WEEK 2024) - "In upcoming years, new products will likely be available that will further help physicians address IgAN at the pathogenic level. Data from 454 audited patient charts were collected in partnership with 142 US nephrologists in January 2024 and in partnership with an additional 105 US nephrologists in February 2024 via online surveys. With the approvals of delayed-release oral budesonide and sparsentan in IgAN, most nephrologists (80%) indicate that they feel better equipped to treat their IgAN patients. Nephrologists continue to see an unmet need in the IgAN space, leaving room for new market entrants to effectively treat the root cause of the disease and further enable physicians to individualize treatments."

Glomerulonephritis • IgA Nephropathy • Inflammation • Renal Disease • CFB

Long-Term Results from an Open-Label Extension Study of Atacicept for the Treatment of IgA Nephropathy. (PubMed, J Am Soc Nephrol) - No abstract available

Journal • Glomerulonephritis • IgA Nephropathy • Renal Disease

Current status of BAFF targeting immunotherapy in B-cell neoplasm. (PubMed, Int J Clin Oncol) - "Therefore, BAFF-targeted therapies, such as belimumab, atacicept, and tabalumab, are being explored in clinical trials for conditions like chronic lymphocytic leukemia (CLL) and multiple myeloma. 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."

IO biomarker • Journal • Review • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Multiple Myeloma • Oncology

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

NEW B CELL-TARGETED THERAPIES FOR MULTIPLE SCLEROSIS (AUTO 2024) - "The recent interest in the key role of B cells in MS has primarily been evoked by the beneficial and profound anti-inflammatory effects of rituximab, a chimeric monoclonal antibody (mAb) targeting the B cell surface marker CD20, observed in patients with relapsing-remitting (RR) MS. This has been reaffirmed by clinical trials with less immunogenic and more potent humanized and fully human B cell-depleting mAbs targeting CD20, namely ocrelizumab and ofatumumab...Ublituximab, a movel third-generation anti-CD20 chimeric glycoengineered IgG1 mAb has recently shown high efficacy and favorable safety and is currently approved for relapsing MS...Frexalimab, a novel anti-CD40 ligand antibody that reduces the activation of B and other immune cells, has recently shown significantly reduced disease activity in a phase-2 trial in relapsing MS. On the other hand, targeting B cell cytokines with the fusion protein atacicept resulted in increased MS disease activity, highlighting the..."

IO biomarker • CNS Disorders • Epstein-Barr Virus Infections • Inflammation • Multiple Sclerosis • CD40LG

Phase 2b ORIGIN Study Open Label Extension with Atacicept in Patients with IgA Nephropathy and Persistent Proteinuria: Week 72 Interim Analysis (ERA-EDTA 2024) - "At 72 weeks, treatment with atacicept 150 mg was associated with sustained eGFR stability and deepening UPCR reductions, as well as a reversal of the downward eGFR decline in the placebo switch group. Sustained reductions in hematuria were also observed. The open-label extension showed a favorable safety profile similar to the double-blind period."

Clinical • P2b data • Glomerulonephritis • IgA Nephropathy • Infectious Disease • Lupus Nephritis • Renal Disease

Impact of Atacicept on Hematuria in IgA Nephropathy: Post-Hoc Analysis of the Phase 2b ORIGIN Study (ERA-EDTA 2024) - "In a post-hoc analysis, atacicept treatment was associated with hematuria resolution at 36 weeks in a substantially greater percentage of participants as compared with placebo, with improvements seen as early as 4 weeks. These results add to the growing body of evidence supporting atacicept as a potential disease-modifying treatment for IgAN. Atacicept 150 mg is currently being evaluated in a global Phase 3 randomized placebo-controlled trial."

P2b data • Retrospective data • Glomerulonephritis • IgA Nephropathy • Renal Disease

Vera Therapeutics Receives U.S. FDA Breakthrough Therapy Designation for Atacicept in Immunoglobulin A Nephropathy (IgAN) (GlobeNewswire) - "Vera Therapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to atacicept for the treatment of IgAN. The designation reflects the FDA’s determination that, based on an assessment of data from the Phase 2b ORIGIN clinical trial of atacicept for IgAN, atacicept may demonstrate substantial improvement on a clinically significant endpoint over available therapies for patients with IgAN....As part of the Breakthrough Therapy Designation request, the FDA reviewed data from the Phase 2b ORIGIN trial..."

Breakthrough therapy • IgA Nephropathy • Immunology