Jonathan Barratt, PhD, FRCP

future of IgAN treatment, highlighting the BlyS/APRIL axis.

The Future of IgA Nephropathy Treatment

This is a video synopsis/summary of a panel discussion involving Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD.

In this discussion, Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD anticipate the imminent release of phase three data for drugs targeting the BAFF (B-cell activating factor) and APRIL (A proliferation-inducing ligand) axis, particularly April only and April and BAFF approaches. They foresee the potential availability of these drugs on the market within the next 24 months if they prove effective and gain approval.

The conversation shifts to safety concerns, emphasizing the favorable risk profile regarding hypogammaglobulinemia and infections associated with BAFF and APRIL inhibitors. Notably, the discussion touches on the crucial issue of vaccine responsiveness, highlighting preliminary data suggesting a less pronounced negative impact on vaccine responses compared to CD20-depleting therapies, especially relevant during the COVID-19 pandemic.

Dr Barratt concludes by urging viewers to keep a close eye on developments in the BAFF/APRIL axis, predicting its integration into the daily practice of healthcare professionals specializing in kidney diseases. He highlights the excitement surrounding established drugs like sibeprenlimab and atacicept, as well as promising newcomers like povetacicept, encouraging viewers to stay informed about forthcoming clinical data in this rapidly evolving field.

Video synopsis is AI-generated and reviewed by HCPLive editorial staff.

Videos

Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD, discuss the future of IgAN treatment, highlighting the BlyS/APRIL axis.

clinical trial data regarding the use of povetacicept for the treatment of IgAN.

Use of Povetacicept in Treatment of IgA Nephropathy

Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD, discuss the latest data on drugs targeting the B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) axis in IgA nephropathy (IgAN), presented at the American Society of Nephrology (ASN) meeting. The conversation highlights the growing interest and excitement in the nephrology community about these emerging therapies.

Dr Barratt mentions recent data on sibeprenlimab and povetacicept and emphasizes the significant attention these drugs received at the ASN meeting. He specifically discusses the promising results from sibeprenlimab, showcasing consistent and effective APRIL inhibition, resulting in a reduction in galactose-deficient IgA1 (Gd-IgA1) and translation to reduced proteinuria.

Dr Rovin provides insights into the presentation of data on povetacicept, emphasizing its impressive proteinuria reduction, even at what is referred to as a "low dose." Both experts acknowledge the need for further dose-ranging studies to determine optimal dosing.

The discussion extends to the potential applications of these drugs beyond IgAN. Dr Barratt highlights a patient with membranous nephropathy treated with povetacicept, showing a significant reduction in anti-PLA2R titers, suggesting a potential broader impact on autoantibody-mediated diseases.

The experts discuss the ability of these drugs to target different cell populations, providing a unique advantage in diseases where both pathogenic antibodies and autoantibodies play a role. Dr Barratt emphasizes the potential benefits in lupus, envisioning combined approaches with BAFF and APRIL inhibition.

Dr Rovin concludes by expressing excitement about the multifaceted applications of these drugs in various diseases and suggests rethinking the use of immunosuppression, aiming for effective treatment with reduced overt immunosuppression. The conversation underscores the transformative potential of BAFF and APRIL inhibitors in reshaping the landscape of nephrology therapeutics across multiple diseases.

Drs Jonathan Barratt and Brad Rovin comment on clinical trial data regarding the use of povetacicept for the treatment of IgAN.

review clinical trials for new and emerging treatments for IgAN, highlighting atacicept and telitacicept.

Clinical Trial Results From Emerging Therapies in IgA Nephropathy

The discussion shifts to the emerging class of drugs targeting the B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) axis in IgA nephropathy (IgAN). Dr Barratt prompts Dr Rovin to share his impressions from a high-level perspective on these new therapeutics, considering the variety of drugs available, such as APRIL-only therapeutics, zigakibart, sibeprenlimab, and combinations of BAFF and APRIL inhibitors.

Dr Rovin acknowledges the challenge of assessing these drugs collectively due to variations in patient populations and study phases. However, he notes that the aggregate data suggests a beneficial effect from targeting both cytokines. His primary considerations in evaluating these drugs include efficacy, convenience, adherence, and side-effect profiles.

Dr Barratt shares his optimism about this therapeutic pathway, foreseeing its fundamental role in IgAN and its potential extension to other disease areas. He emphasizes the promising concordance in side-effect profiles and the anticipated ability to modulate these cells safely and effectively. Dr Rovin expresses agreement and expands the discussion to the broader implications of this therapeutic approach. He envisions applications beyond IgAN, including lupus and membranous nephropathy, suggesting a shift towards considering glomerular diseases as a whole rather than isolated entities. Both experts highlight the need for innovative trial designs, drawing parallels with basket trials in oncology, to explore shared pathways across various nephrological conditions, particularly in the context of rare diseases.

Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD, review clinical trials for new and emerging treatments for IgAN, highlighting atacicept and telitacicept.

Nephrology experts explore the role of dual inhibition of BlyS and APRIL in the treatment of IgAN, and how this can impact disease pathogenesis.

Dual Inhibition of BlyS and APRIL in IgA Nephropathy

Jonathan Barratt, PhD, FRCP, and Brad Rovin, MD, discuss the modulation of B cells, specifically targeting cytokines Baff and April, crucial for IgA class switch recombination. Dr Rovin draws on his experience in lupus nephritis, where the Baff inhibitor Belimumab showed efficacy in inducing renal responses and preserving kidney function. He highlights the exciting data emerging from BAFF and APRIL inhibitors, particularly in the context of IgA nephropathy (IgAN).

The discussion delves into the novel class of drugs that modulate B cells and inhibit BAFF and APRIL simultaneously. Dr Rovin expresses fascination with the data indicating a depletion of galactose-deficient IgA, a subset thought to be responsible for kidney damage. He speculates on the mechanisms by which these drugs may selectively target aberrant IgA molecules, suggesting a potential sensitivity of specific B cell clones to growth factors.

Dr Barratt emphasizes the importance of evaluating both efficacy and safety when assessing these drugs. The safety concern with B cell modulation revolves around potential effects on IgG, which is crucial for lifelong immunity and immunological memory. However, the data suggests that IgG is relatively protected, minimizing the risk of hypogammaglobulinemia associated with some B cell-depleting therapies.

The conversation touches on the autoimmune aspect of IgAN, where aberrant IgA molecules may induce IgG autoantibodies. Drawing parallels with lupus, Dr Rovin discusses the potential impact of Baff inhibition on autoantibody production and the long-term benefits of having a therapy that sticks around to manage relapsing autoimmune diseases like IgAN.

Both experts agree on the need for longer-term maintenance therapies in glomerular diseases like IgAN and emphasize the importance of biomarkers for monitoring disease activity and progression. The discussion reflects a nuanced approach to treatment, acknowledging the complexities of these autoimmune conditions and the necessity for personalized, sustained therapeutic strategies.

Jonathan Barratt, PhD, FRCP

Articles