Nephrology Month in Review: May 2024
A field that has undergone a revolution in pharmacological therapy and understanding of optimized management in recent years, nephrology has been given many reasons to celebrate in recent years. However, the month of May 2024, which hosted the National Kidney Foundation ’s (NKF) Spring Clinical Meetings and the 61st European Renal Association (ERA) Congress, stands out as a turning point for the field in many ways.
In our nephrology month in review for May 2024, we spotlight the biggest news from these meetings, including the latest updates in IgA nephropathy (IgAN), C3 glomerulopathy(C3G), chronic kidney disease, and more!
IgA Nephropathy
After stealing the spotlight at ASN Kidney Week 2023, a new 2-year analysis of data from the PROTECT trial headlined NKF Spring Clincial Meetings. The 110-week data, which Brad Rovin , MD, presented, suggest patients with IgAN receiving sparsentan (Filspari; Travere Therapeutics ) were nearly 3-fold more likely to achieve complete remission (31%) compared to patients receiving irbesartan (11%) by week 110 (relative risk, 2.5; 95% CI, 1.6 to 4.1).
Data from the phase 3 ALIGN trial suggests use of atrasentan ( Chinook Therapeutics ) was associated with a 36.1% reduction in proteinuria relative to placebo therapy among patients with?IgAN.
Presented at ERA 24 by hiddo lambers heerspink , results of the trial analysis, which included the first 270 patients from the 340-patient trial, indicate use of atrasentan was associated with significant reductions in proteinuria. If approved, the endothelin A receptor agonist could provide an additional option for patients with IgAN. According to a release from Novartis, the company expects to file a submission for atrasentan in IgAN during the first half of 2024.
Data from the phase 1/2 ADU-CL-19 trial suggests zigakibart ( Chinook Therapeutics ) was well-tolerated through 52 weeks, with results also pointing to potential efficacy benefits in patients with IgA nephropathy. The ongoing phase 1/2 trial was launched in 2019 with parts 1 and 2 of the trial designed to assess single and multiple ascending doses of zigakibart in healthy adults. According to data from ERA 24, a total of 40 patients were included in cohorts 1 and 2 for the trial and completed 52 weeks of treatment.
Results, which were presented by Jonathan Barratt , MD, indicate zigakibart was well-tolerated among patients included in the trial. Assessments of treatment-emergent adverse events revealed such events occurred among 85% of patients, but none of these events were considered serious or led to study drug discontinuation. Further analysis indicated use of zigakibart was associated with durable reductions in serum levels of IgA, IgM, and IgG of 67%, 78%, 35%, respectively, at 52 weeks among patients with IgA nephropathy. Additionally, assessments of proteinuria revealed zigakibart was associated with a 53% clinically meaningful reduction in proteinuria in the healthy adults from cohorts 1 and 2.
C3 Glomerulopathy
A multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 trial launched in 2021, results of the APPEAR-C3G?were presented at ERA 24 and concluded use of iptacopan (Fabhalta; 诺华 ) was associated with a 35.1% reduction in proteinuria among patients with?C3 glomerulopathy. Analysis of secondary endpoints of interest revealed a 7-fold increase in likelihood of meeting the composite kidney outcome with iptacopan relative to placebo therapy (OR, 7.145; 95% CI, 1.429 to 35.723; nominal 1-sided?P?= .0083).
Although the trial is set to continue with a 6-month, open-label period, results of the 6-month double-blind portion of the study provide hope to a community of nephrologists and patients that is currently without any approved therapies. According to Novartis, regulatory submissions for iptacopan in C3G are expected in the second half of 2024.
A phase 2 trial suggests use of pegcetacoplan ( Apellis Pharmaceuticals ) in patients with post-transplant recurrence of?C3 glomerulopathy and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) has returned positive results.
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The 1-year results of the NOBLE trial build on previous 12-week data from the trial and indicate the benefits observed with pegcetacoplan among this patient population persisted through the 40-week double blind portion of the trial. Presented at ERA 24, results of the trial demonstrate use of pegcetacoplan was associated with reduction disease activity in post-transplant C3G and IC-MPGN, with benefits persisting through the 40-week double-blind period.
Other Nephrotic Diseases
At ERA 24, Glenn Chertow , MD, of Stanford Medicine, presented data from a phase 2b trial of clazakizumab, an Il-6 inhibitor from CSL , in patients receiving maintenance dialysis. Named the POSIBIL6ESKD trial, the trial assessed use of the agent for reducing cardiovascular risk in the aforemntioned patient population.
Results of the phase 2b portion of the indicate use of clazakizumab was associated with clinically significant reductions in serum hs-CRP of 86%, 90%, and 92% at 12 weeks among those receiving the 2.5 mg, 5 mg, and 10 mg doses, respectively, with no unexpected safety outcomes based on previous research of the agent.
Although not a randomized controlled trial assessing pharmacologic interventions, a study on antinephrin autoantibodies suggests presence or lack thereof could aid in the prediction of disease activity. The study, presented at ERA 24 by @Nicola M. Tomas, MD, concluded the presence of circulating antinephrin autoantibodies were common and appeared to be markers of disease activity in patients with minimal change disease and primary focal segmental glomerulosclerosis.
Chronic Kidney Disease
Although news from across the spectrum of nephrotic disease was spotlighted during ERA 24, the hype and attention the meeting received from communities beyond nephrology was driven primarily by a single agent: semaglutide (Ozempic, Wegovy; 诺和诺德 ). At the meeting, the long-awaited FLOW trial was debuted in a special session by 8 trial investigators providing a comprehensive overview of the study’s results and intricacies.
This is not the only way semaglutide made waves during the meeting—a kidney specific outcomes analysis of the landmark SELECT trial further evidenced the renoprotective benefits of GLP-1 receptor agonist use. As part of our coverage of the meeting and results readout, the editorial team of HCPLive Endocrinology detailed the latest data through a pair of articles, on-site interviews with principal investigators, and a pair of expert-led podcasts. Check out all of our associated coverage, including preview clips, below:
Lead Investigator Interview:?Vlado Perkovic, MBBS, PhD: Semaglutide's Role in CKD Based on FLOW Results
Lead Investigator Interview: Helen Colhoun, MD: Semaglutide 2.4 mg (Wegovy) Reduces Kidney Outcomes in SELECT
Diabetes Dialogue:?FLOW Trial and Semaglutide's Benefit in Chronic Kidney Disease
Don’t Miss a Beat: Semaglutide and the Future of Kidney Disease, with Brendon Neuen, MBBS, PhD