Highlights of ASN Kidney Week 2022

The American Society of Nephrology (ASN) Kidney Week 2022 will be held in Orlando, Florida from November 3-6. A series of conferences will be hosted in a hybrid format with more than 2,500 poster presentations and an expected attendance of over 10,000 nephrology professionals.

ASN President Dr. Susan E. Quaggin anticipates that the event will not only provide updates on the standard of care, but will also introduce new discoveries and major medical breakthroughs.

Some promising trial highlights worth tuning in for include: Sparsentan for FSGS and IgA Nephropathy, Voclosporin for lupus nephritis, anti-miR-17 oligonucleotide for ADPKD, and Telitacicept for systemic lupus erythematosus (SLE).

Sparsentan for FSGS and IgA Nephropathy

Emerging evidence indicates strong nephroprotection by dual antagonism of the endothelin type A and angiotensin type 1 receptors with sparsentan (SP). Sparsentan has been granted orphan drug status in the United States and Europe for the treatment of focal segmental glomerulosclerosis (FSGS) and immunoglobulin A nephropathy (IgAN) and is currently being evaluated in the pivotal phase III DUPLEX study for FSGS and phase III PROTECT study for IgAN. The FDA is currently reviewing both indications. If approved, sparsentan may be the first drug approved for FSGS and IgAN.

Long-term Outcome Data of Voclosporin

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus, Voclosporin is the first oral drug approved by FDA under this indication. The drug has a dual mechanism of action by inhibiting T-cell activation and cytokine production and promoting the stabilization of renal podocytes. Several trials on Voclosporin will be presented during the event, including the Phase 3 AURORA 1 and AURORA 2 studies which assess the long-term safety and efficacy over 3 years of double-blinded treatment of LN using voclosporin. Results show that voclosporin was well-tolerated over 3 years of treatment, with significant reductions in proteinuria. 

Anti-miR-17 Oligonucleotide RGLS8429 for ADPKD

Autosomal dominant polycystic kidney disease (ADPKD) is caused by PKD1 or PKD2 gene mutations, causing gradual deterioration of kidney functions, leading to end-stage renal disease. The inhibition of miR-17 family of miRNAs could attenuate cyst growth in preclinical ADPKD models. Although treatment with the first-generation anti-miR-17 oligonucleotide RGLS4326 (1mg/kg) resulted in a statistically significant benefit in ADPKD patients. However, further investigations found that RGLS4326 would lead to off-target inhibition of the neuroreceptor AMPA-R, causing dose-limiting CNS toxicity in mice and monkeys. The discovery of the next-generation anti-miR-17 oligonucleotide RGLS8429, which has a similar efficacy profile as RGLS4326 without the affinity for AMPA-R, will be discussed in this event.

NGAL Biomarker for Acute Kidney Injury (AKI) 

The biomarker neutrophil gelatinase-associated lipocalin (NGAL) is designed to assess the risk of moderate/severe AKI in critically ill patients (3 months to 22 years of age) within the first 24 hours of admission to the intensive care unit. Urine NGAL has been associated with AKI and offers a less invasive screening mechanism for AKI. During ASN Kidney Week 2022, the NGAL biomarker for AKI research, including clinical chemistry assay, ELISA kits, and antibodies for early drug development and clinical research, will be showcased. The biomarker is one of six urinary biomarkers in the kidney safety composite measure, CDER encourages safety biomarkers for monitoring drug-induced renal tubular injury in early clinical drug development.

Hope to Alleviate Metabolic Acidosis in Chronic Kidney Disease (CKD) 

The Phase 3 VALOR-CKD clinical trial for renal outcomes trial has been selected for an oral presentation in the High-Impact Clinical Trials session, reporting of top-line data from the trial, which determines if veverimer slows CKD progression in patients with metabolic acidosis associated with CKD. Veverimer is a non-absorbed, orally-administered polymer designed to slow CKD progression in patients with metabolic acidosis and CKD. This drug was once considered deficient by the FDA, leading to the rejection of filing for approval of a treatment for metabolic acidosis in patients with CKD in 2020. Revised clinical data will be presented in an oral abstract session.

Phase 2 Clinical Trial of Telitacicept

Systemic lupus erythematosus (SLE) is the principal indication of Telitacicept. The Phase 2, randomized, double-blind, placebo-controlled clinical trial evaluating the efficacy and safety of Telitacicept compared with placebo when added to standard therapy in high-risk for progression IgA nephropathy patients. 

The primary endpoint will evaluate the change of proteinuria at week 24. The secondary endpoints will assess the changes in estimated GFR from baseline over 24 weeks and levels of IgA from baseline at week 24. The incidence of adverse events will also be documented. In this trial, Telitacicept is expected to reduce proteinuria in patients with IgA nephropathy and reduce the risk of future kidney progression.

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