Kidney Week

Abstract: TH-PO1075

Efficacy and Safety of SEL-212 in Patients with Refractory Gout and CKD: A Post Hoc Analysis from the Two Phase 3 DISSOLVE Studies

Session Information

• CKD: Therapeutic Advances
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

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

Authors

• Khanna, Puja, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States

Puja Khanna, MD, MPH

• Johnson, Richard J., Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Richard J. Johnson, MD

• Azeem, Rehan, Sobi, Waltham, Massachusetts, United States

Rehan Azeem, MBBS, MPH

• Falk, Aletta, Sobi, Stockholm, Sweden

Aletta Falk, MSc

• Desai, Bhavisha, Sobi, Waltham, Massachusetts, United States

Bhavisha Desai, PharmD

• Santin-Janin, Hugues, Sobi, Basel, Switzerland

Hugues Santin-Janin, PhD

• Baraf, Herbert, The Center for Rheumatology and Bone Research, Rheumatology, Wheaton, Maryland, United States

Herbert Baraf, MD

• Kivitz, Alan J., Department of Rheumatology, Altoona Center for Clinical Research, Duncansville, Pennsylvania, United States

Alan J. Kivitz, MD

Background

Chronic kidney disease (CKD) is common in patients with gout, especially in patients with chronic refractory gout (CRG), but evidence on the management of gout in these patients is limited (Stamp LK, et al. Nat Rev Rheumatol 2021;17:633). Here, we present Phase 3 efficacy and safety data on the investigational uricase-based therapy SEL-212 in patients with CRG and CKD.

Methods

DISSOLVE I (NCT04513366) and DISSOLVE II (NCT04596540) investigated the efficacy and safety of SEL-212, a two-component infusion therapy of pegadricase (a pegylated uricase) and immune-tolerizing nanoparticles containing sirolimus in the treatment of CRG. Two doses of SEL-212 or placebo were administered every 28 days for up to 6 treatment periods (TPs) in DISSOLVE II, or up to 12 TPs in DISSOLVE I. The primary endpoint was serum uric acid reduction below 6 mg/dL for at least 80% of the time during TP6. Secondary endpoints assessed sUA reduction and related outcomes. In this post hoc analysis, efficacy and safety data from both studies were pooled and outcomes in patients with CKD stage 3 at baseline were analyzed using the Mantel-Haenszel test with randomization of tophus presence (yes/no) with a two-sided error rate of α=2.5% to account for the two comparisons of study drug against placebo.

Results

Among 265 patients in DISSOLVE I and II, 61 had CKD stage 3. The proportion of patients with CKD stage 3 who met the primary endpoint was broadly comparable to the overall population: 52% vs 51% in the high dose treatment arm, 61% vs 43% in the low dose arm, and 10% vs 8% in the placebo arm. Mean glomerular filtration rates were stable in both arms from baseline to TP6 (Fig. 1).

Conclusion

Data from DISSOLVE I and II endorsed the efficacy and safety of SEL-212 in patients with gout refractory to conventional therapy with CKD stage 3. Further studies are needed to establish the use of this novel combination product in refractory gout with end-stage kidney damage.

Funding

• Commercial Support – Sobi and Selecta Biosciences, Inc