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Kidney Week

Abstract: TH-PO1094

Nanoencapsulated Sirolimus Plus Pegadricase (NASP) Reduces Gout Clinical Manifestations in Patients with Uncontrolled Gout (UG) and Stage 3 CKD

Session Information

Category: CKD (Non-Dialysis)

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

Authors

  • Elfadawy, Nissreen, UH Geauga Medical Center, Chardon, Ohio, United States
  • Khanna, Puja, University of Michigan Division of Rheumatology, Ann Arbor, Michigan, United States
  • Azeem, Rehan, Sobi Inc, Waltham, Massachusetts, United States
  • Peace, Ben, Sobi, Stockholm, Sweden
  • Desai, Bhavisha, Sobi Inc, Waltham, Massachusetts, United States
  • Qazi, Yasir A., University of Southern California Keck School of Medicine, Los Angeles, California, United States
Background

Patients (pts) with UG often have chronic kidney disease (CKD). CKD limits urate-lowering therapy efficacy in UG, amplifying the unmet needs for pts with CKD. NASP (formerly SEL-212) is an investigational, novel, every 4-wk (Q4W), sequential 2-component infusion therapy consisting of targeted nanoencapsulated sirolimus (NAS) and pegadricase (P) that reduces serum uric acid (sUA). NASP reduced sUA levels in pts with stage 3 CKD (CKD3) in the phase 3 DISSOLVE I and II (DI/II) studies (NCT04513366, NCT04596540; Khanna et al, ASN 2024). Here, we report additional efficacy and safety outcomes.

Methods

In DI/II, pts with UG were randomized 1:1:1 to receive NASP (0.15 mg/kg [high-dose; HD] or 0.1 mg/kg [low-dose; LD] NAS plus 0.2 mg/kg P) or placebo (PBO) Q4W for six treatment periods. This post hoc analysis included pts with CKD3 (eGFR 30–59 mL/min/1.73 m2).

Results

Of 265 pts in the intent-to-treat (ITT) populations, 61 had CKD3 (HD NASP: n=20; LD NASP: n=18; PBO: n=23); baseline disease burden was high (Table). A larger proportion of NASP- vs PBO-treated pts had a complete resolution of tophi by wk 24 (HD NASP: 39%; LD NASP: 53%; PBO: 2%; Table). Compared to PBO, the least-square mean difference (standard error) in the change in number of tender/swollen joints from baseline to wk 24 was −3.1/−0.9 (1.52/0.98) for HD NASP, −3.8/−0.4 (1.53/0.98) for LD NASP. Gout flares (GFs) were similar in NASP- and PBO-treated pts during wk 1–20; NASP-treated pts had fewer GFs in wk 21–24. Safety was similar to the ITT population (Table), with only one case of proteinuria in each NASP arm (not considered drug related).

Conclusion

NASP was well tolerated and reduced disease burden in pts with UG and CKD.

Funding

  • Commercial Support – The DISSOLVE I and II (NCT04513366 and NCT04596540) studies were jointly funded by Sobi and Selecta Biosciences, Inc. Sobi funded medical writing and editorial assistance.

Digital Object Identifier (DOI)