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Kidney Week

Abstract: TH-PO589

Updated Results with Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist, in Primary Membranous Nephropathy (RUBY-3 Study)

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Madan, Arvind, Central Florida Kidney Specialists, Orlando, Florida, United States
  • Yalavarthy, Rajesh, Western Nephrology, Arvada, Colorado, United States
  • Kim, Dong Ki, Seoul National University Hospital, Seoul, Korea (the Republic of)
  • Moon, Ju young, Kyung Hee University Hospital at Gangdong, Seoul, Korea (the Republic of)
  • Park, Inwhee, Ajou University School of Medicine, Suwon-Si, Gyeonggi-do, Korea (the Republic of)
  • Mandayam, Sreedhar A., The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
  • Cortazar, Frank B., New York Nephrology Vasculitis and Glomerular Center, Albany, New York, United States
  • Kim, Sung Gyun, Hallym University Sacred Heart Hospital, Anyang-Si, Gyeonggi-do, Korea (the Republic of)
  • Davies, Rupert Hugo, Alpine Immune Sciences, Inc., Seattle, Washington, United States
  • Enstrom, Amanda M., 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
  • Peng, Stanford L., Alpine Immune Sciences, Inc., Seattle, Washington, United States
  • Tumlin, James A., NephroNet Clinical Trials Consortium, Atlanta, Georgia, United States
Background

Inhibition of BAFF and/or APRIL has shown promise in IgA nephropathy (IgAN), lupus, lupus nephritis (LN), and primary membranous nephropathy (pMN), and has the potential to exert a disease-modifying effect. Povetacicept (ALPN-303) is an Fc fusion protein of a variant TACI domain engineered for more potent dual BAFF/APRIL inhibition vs WT TACI or anti-BAFF/-APRIL antibodies. Povetacicept has been associated with on-target reductions in Ig levels and antibody-secreting cells in healthy volunteers. In an initial case report of pMN from the ongoing RUBY-3 study of povetacicept (NCT05732402), immunological remission was achieved at 22 wk, with anti-PLA2R1 levels reduced to below the limit of detection (Tumlin J, et al. Poster TH-PO1125 presented at ASN 2023).

Methods

RUBY-3 is an open-label, multiple ascending dose, ph 1b/2a study of povetacicept 80 or 240 mg SC Q4W for 24 wk, followed by a 28-wk extension; participants meeting prespecified criteria at 48 wk may enter an optional 52-wk extension. Eligible participants are aged ≥18 y with IgAN, pMN, LN, or ANCA-associated vasculitis (biopsy-confirmed diagnosis required for IgAN, pMN, and LN). Participants must be 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 1 Mar 2024, 3 participants with pMN have enrolled at the povetacicept dose level of 80 mg SC Q4W; 1 has completed ≥40 wk and 2 have completed <4 wk. Povetacicept has been well tolerated with multiple dosing, with no serious or severe adverse events. In the participant with the longest follow-up, significant reduction in anti-PLA2R1 has continued to be observed following achievement of immunological remission at 22 wk, with levels remaining below the limit of detection. Updated safety, efficacy, PK, and PD findings will be reported at the time of presentation.

Conclusion

In these initial findings, povetacicept demonstrates promising activity in pMN, strongly supporting its further development in autoantibody-associated glomerulonephritis.

Funding

  • Commercial Support – Alpine Immune Sciences, Inc.