Early RUBY-3 Data Shows Promise for Povetacicept in Glomerulonephritis


Preliminary data from the open-label RUBY-3 trial were presented at the American Society of Nephrology Kidney Week 2023.

James Tumlin, MD | Credit: Georgia Nephrology

James Tumlin, MD
Credit: Georgia Nephrology

Data from the RUBY-3 trial suggests use of povetacicept, an enhanced dual BAFF/APRIL antagonist, could prove useful in the management of adult patients with autoantibody-associated glomerulonephritis.

Presented at the American Society of Nephrology Kidney Week 2023, results of the phase 1a/2b trial, which included patients with IgA nephropathy, primary membranous nephropathy, and lupus nephritis, indicate use of povetacicept was well-tolerated, with investigators pointing out reductions in urinary protein-to-creatinine ratio and no serious adverse events observed in the trial.1

“In this initial experience, low-dose povetacicept at 80 mg has been well tolerated and demonstrates highly encouraging improvements in UPCR and disease biomarkers in IgA nephropathy, with early evidence suggesting remission," said James Tumlin, MD, professor of medicine at Emory University School of Medicine as well as the founder and chief executive officer of NephroNet Clinical Trials Consortium.2 “These findings suggest a highly compelling development profile for povetacicept based upon a rapid reduction in the key pathogenic biomarker Gd-IgA1, marked and clinically meaningful reductions in UPCR, and a once-a-month dosing regimen.”

RUBY-3 was an open-label study launched in March 2023 with the intent of exploring the safety and efficacy of povetacicept 80 mg or 240 mg every 4 weeks for 24 weeks, with an optional 24-week extension period. Sponsored by Alpine Immune Sciences, the trial enrolled patients aged 18 years or older with biopsy-confirmed IgA nephropathy, primary membranous nephropathy, and lupus nephritis. Additional inclusion criteria for the trial required patients to be on maximally tolerated ACEi/ARB therapy, have well-controlled blood pressure, and be receiving disease-specific immunosuppressive therapy where applicable.1

The primary objective for the trial was safety assessment. Secondary outcomes of interest included pharmacokinetics, pharmacodynamics, immunogenicity, biomarkers, and efficacy of the agent.1

At Kidney Week 2023, data presented by Tumlin indicated 20 participants with IgA nephropathy had been enrolled, with 12 having received povetacicept, including 5 with available UPCR at 24 weeks. Among this group, use of povetacicept was associated with clinically meaningful improvements in proteinuria, with a 53.5% reduction from baseline in UPCR observed at 24 weeks.1

A release from Alpine Immune Sciences also pointed 80% had achieved remission, which was defined as UPCR less than 0.5 g/g and 50% or greater reduction in UPCR from baseline with stable renal function. Additionally, results indicated treatment with povetacicept 80 mg was also associated with more than a 60%reduction in Gd-IgA1 as well as stable eGFR) (+7.1% from baseline at 24 weeks). Alpine Immune Sciences also noted a single patient with primary membranous nephropathy has also been enrolled and treated with povetacicept 80 mg. This patient had achieved immunological remission.1

Initial safety analyses from RUBY-3 indicate povetacicept was well tolerated, with no reported administration-associated reactions, no instances of IgG < 3 g/L, and no severe infections. Alpine Immune Sciences detailed plans to continue enrollment for the elevated dose of povetacicept and expects initial data in the first half of 2024.1

“Based on this data, advancement of povetacicept to a pivotal trial in IgA nephropathy, where it has already accumulated a reasonably sized clinical experience, seems urgently warranted,” added Jonathan Barratt, MD, Mayer Professor of Renal Medicine at the University of Leicester.2 “The initial findings in primary membranous nephropathy, a disease with no approved therapies, are equally encouraging. Further study is clearly warranted and confirmation of the results in additional pMN patients, along with correlation with renal outcomes, may facilitate a rapid development path.”


  1. Tumlin JA, Davie RH, Enstrom AM, et al. Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist, in Autoantibody-Associated Glomerulonephritis (GN). Paper Presented at: American Society of Nephrology Kidney Week 2023. November 1-5, 2023
  2. Alpine Immune Sciences. Alpine Immune Sciences Presents Initial Clinical Data on Povetacicept in Autoimmune Glomerulonephritis in a Late-Breaking Poster Session at the American Society of Nephrology Kidney Week 2023. Alpine Immune Sciences. November 2, 2023. Accessed November 4, 2023. https://ir.alpineimmunesciences.com/news/news-details/2023/Alpine-Immune-Sciences-Presents-Initial-Clinical-Data-on-Povetacicept-in-Autoimmune-Glomerulonephritis-in-a-Late-Breaking-Poster-Session-at-the-American-Society-of-Nephrology-Kidney-Week-2023/default.aspx.
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