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Kidney Week

Abstract: TH-PO1092

Effect of Nanoencapsulated Sirolimus Plus Pegadricase (NASP) on Kidney Outcomes: Results from the Phase 3 DISSOLVE Studies

Session Information

Category: CKD (Non-Dialysis)

  • 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Rajpal, Minesh, Southwest Kidney Institute Central Phoenix, Phoenix, Arizona, United States
  • Strand, Vibeke, Stanford University, Palo Alto, California, United States
  • Azeem, Rehan, Sobi Inc, Waltham, Massachusetts, United States
  • Peace, Ben, Swedish Orphan Biovitrum AB publ, Stockholm, Stockholm County, Sweden
  • Desai, Bhavisha, Sobi Inc, Waltham, Massachusetts, United States
  • Johnson, Richard J., University of Colorado Denver, Aurora, Colorado, United States
Background

Patients with uncontrolled gout (UG) have higher odds of developing chronic kidney disease (CKD). NASP is a novel, investigational, every 4-week, sequential infusion therapy consisting of targeted immunomodulating, nanoencapsulated sirolimus (NAS) co-administered with pegadricase (a pegylated uricase). Efficacy and safety of NASP in patients with stage 3 CKD (CKD-3) have been presented (Khanna P, et al. ASN 2024). Here we report renal outcomes in patients with CKD-3.

Methods

This post-hoc analysis from DISSOLVE I and II (NCT04513366, NCT04596540) includes patients with CKD-3, randomized 1:1:1 to receive NASP (high-dose [HD]: sequential infusions, 0.15 mg/kg NAS and 0.2 mg/kg pegadricase; low-dose [LD]: sequential infusions, 0.10 mg/kg NAS and 0.2 mg/kg pegadricase) or placebo (PBO) every 4 weeks for a total of 6 treatment periods. Outcomes include renal function tests and CKD stage.

Results

Among 265 treated patients in DISSOLVE I and II, 61 had CKD-3. Across all treatment groups, median BUN levels remained consistent from baseline to Week 24 (Table). A slight improvement in median serum creatinine was observed in HD and LD NASP groups from baseline to Week 24, while PBO slightly worsened (Table). There was 1 case of proteinuria in each NASP arm, considered not drug-related. At Week 24, 5 (25%) patients in HD improved to stage 2 and 1 (5%) improved to stage 1. In LD, 5 (27.8%) improved to stage 2. In PBO, 2 (8.7%) improved to stage 2 (Table). Median BP stayed consistent amongst all three treatment groups from baseline to Week 24 (Table). Adverse events were similar to the intent-to-treat population.

Conclusion

These data show stable renal function over the study period in NASP-treated patients with more patients having an improvement in CKD stage compared to PBO. Findings here suggest NASP may be a uricase treatment option for patients with UG and CKD-3.

Funding

  • Commercial Support – The DISSOLVE I & II (NCT04513366 and NCT04596540) studies were jointly funded by Sobi and Selecta Biosciences, Inc. Sobi funded Medical Writing and Editorial assistance. Sobi reviewed and provided feedback on the abstract.

Digital Object Identifier (DOI)