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Kidney Week

Abstract: TH-PO1125

Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist, in Autoantibody-Associated Glomerulonephritis (GN)

Session Information

  • Late-Breaking Posters
    November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Tumlin, James A., NephroNet Clinical Trials Consortium, Atlanta, Georgia, United States
  • Singh, Harmeet, Western Nephrology, Arvada, Colorado, United States
  • Cortazar, Frank B., New York Nephrology Vasculitis and Glomerular Center, Watervliet, New York, United States
  • Madan, Arvind, Central Florida Kidney Specialists, Orlando, Florida, United States
  • Barratt, Jonathan, University of Leicester, Leicester, United Kingdom
  • Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Zhang, Hong, Peking University First Hospital, Beijing, China
  • Davies, Rupert Hugo, Alpine Immune Sciences, Inc., Seattle, Washington, United States
  • Enstrom, Amanda M., Alpine Immune Sciences, Inc., Seattle, Washington, United States
  • Chunyk, Allison G., Alpine Immune Sciences, Inc., Seattle, Washington, United States
  • Thomas, Heather, Alpine Immune Sciences, Inc., Seattle, Washington, United States
  • Li, Jiahua, Alpine Immune Sciences, Inc., Seattle, Washington, United States
  • Mandayam, Sreedhar A., UT MD Anderson Cancer Center, Bellaire, Texas, United States
Background

Inhibition of BAFF and/or APRIL has shown promise in IgA nephropathy (IgAN), primary membranous nephropathy (pMN), and lupus nephritis (LN), with the potential to exert a disease-modifying effect. Povetacicept (ALPN-303) is an Fc fusion of a variant TACI domain engineered for more potent dual BAFF/APRIL inhibition vs WT TACI or anti-BAFF or -APRIL Abs. In healthy volunteers, povetacicept was well tolerated and reduced Ig (including Gd-IgA1) levels and Ab-secreting cells. This is a report of an open-label, multiple ascending dose experience with povetacicept in GN.

Methods

RUBY-3 (NCT05732402) is a ph 1b/2a study of povetacicept 80 or 240 mg SC Q4W for 24 wk, with an optional 24-wk extension. Eligible participants (pts) are aged ≥18 y with biopsy-confirmed IgAN, pMN, or LN, and on maximally tolerated ACEi/ARB therapy, with well-controlled BP, and disease-specific immunosuppressive therapy where applicable. Primary objective is safety; secondary objectives include PK, PD, immunogenicity, biomarkers, and efficacy.

Results

As of 1Sep23, 12 pts with IgAN and 1 with pMN have enrolled at the lower povetacicept dose level of 80 mg; 6 and 1 pts, respectively, have completed ≥12 wk. The 240-mg IgAN cohort has also begun enrolling. Povetacicept has been well tolerated, with no serious or severe TEAEs, IgG <3 g/L, or administration-related reactions. In IgAN, UPCR was reduced by 30% at 12 wk (n=6) and expected decreases in Ig levels were seen (Fig). The first enrolled pt achieved a urinary protein excretion level below the threshold of detection (<0.56 g/g) by 24 wk, preceded by a 43% reduction in Gd-IgA1 at 4 wk. In pMN (n=1), a 39% UPCR reduction (Fig) and 77% reduction in anti-PLA2R were seen at 12 wk. Updated data will be presented.

Conclusion

Initial experience indicates povetacicept is well tolerated during multiple-dose administration in GN, with highly encouraging early reductions in UPCR and disease-specific biomarkers in pts with IgAN and pMN.

Funding

  • Commercial Support – Alpine Immune Sciences, Inc.