P084 Gout symptom improvements and patient outcomes with SEL-212 in gout refractory to conventional therapy: DISSOLVE I & II phase 3, double-blind, placebo-controlled clinical trials
Authors: Baraf Herbert S B , Khanna Puja , Patel Anand , Sobierska Joanna , Christie Jacquie , DeHaan Wesley , Azeem Rehan , Traber Peter G , Kivitz Alan 
Published: April 2024

Abstract

Background/Aims
Serum uric acid (sUA) ≥6.8 mg/dL often leads to severe clinical manifestations in gout refractory to conventional therapy. Uricase-based therapies can be effective, although immunogenicity can reduce efficacy and increase infusion-reaction risk. SEL-212 is a novel, once-monthly treatment of sequential infusions of tolerogenic nanoparticles containing sirolimus (SEL-110) followed by a pegylated uricase (pegadricase, SEL-037). DISSOLVE I and II (DI and DII) evaluated the safety/efficacy of SEL-212 in adults with refractory gout. Here we report secondary and key safety endpoints.

Methods
DI (US) and DII (Global) were placebo-controlled, double-blind, randomised clinical trials that evaluated a combination of SEL-110 at either 0.15 mg/kg [high-dose] or 0.1 mg/kg [low-dose] with SEL-037 (0.2 mg/kg) in refractory gout. Six-month outcomes included sUA reduction, number of tender/swollen joints, tophus burden, health-related quality-of-life, and safety.

Results
112 participants (96% male, 66% aged ≥50 years, DI) and 153 participants (97% male, 72% ≥50 years, DII) were dosed (Table 1). Mean age was 55 years, 57% (DI) and 67% (DII) had tophi at baseline, and time since gout diagnosis was 12.9 (DI) and 11.0 years (DII). Both SEL-212 doses significantly reduced mean sUA levels versus placebo over 6-months (5.2-5.6 mg/dL in DI and 3.3-4.5 mg/dL in DII, p &lt; 0.001 for all), with marked reductions during the first-treatment period. In DII, tender joints declined significantly between baseline and six-months in the high- and low-dose groups (8.1 joints, p = 0.003; 9.2 joints, p &lt; 0.001, respectively) versus placebo (4.4 joints). Swollen joints were also significantly reduced with high-dose SEL-212 (5.7 joints, p = 0.013) versus placebo (3.4 joints). There were significant improvements in SF-36 physical component score with both SEL-212 doses versus placebo (p ≤ 0.01), while HAQ-DI was significantly improved with low-dose versus placebo (p = 0.018) in DII. In DI non-statistically significant trends favouring SEL-212 across all secondary endpoints were observed. This may reflect the smaller sample size and milder baseline symptom burden of patients in DI versus DII. Infusion reactions occurred in 3.4% of the combined high-dose groups.

Conclusion
SEL-212 was well tolerated and provided significant reductions in mean sUA over time, improvement in SF-36 physical and HAQ-DI measures and reduced the number of tender/swollen joints.

Disclosure
H.S.B. Baraf: Corporate appointments; Sobi, Selecta BioScience, Grünenthal, Fresenius Kabi and Olatec. Member of speakers’ bureau; Horizon Pharmaceuticals. Grants/research support; Horizon Pharmaceuticals, Swedish Orphan Biovitrum. P. Khanna: Consultancies; Horizon, Sobi. Other; Investigator: Selecta Bioscience, Dyve Biosciences. A. Patel: Member of speakers’ bureau; Lexicon Pharmaceuticals. J. Sobierska: Other; Employee of Sobi. J. Christie: Shareholder/stock ownership; GSK Pharma. Other; Employee of Sobi. W. DeHaan: Shareholder/stock ownership; Selecta Biosciences. Other; Employee of Selecta Biosciences. R. Azeem: Shareholder/stock ownership; Selecta Biosciences. Other; Employee of Selecta Biosciences;. P.G. Traber: Shareholder/stock ownership; Selecta Biosciences. Other; Employee of Selecta Biosciences. A. Kivitz: Consultancies; AXDEV Group, Amgen, Pfizer, Janssen, Boehringer Ingelheim, AbbVie, Flexion, Gilead, Grünenthal, Orion, Regeneron, Sun Pharma Advance Research, and ECOR1. Shareholder/stock ownership; Pfizer, GSK, Gilead, Novartis, and Amgen. Member of speakers’ bureau; Merck & Co, Eli Lilly, Novartis, Pfizer, Flexion, AbbVie, Amgen, Genentech, Regeneron, UCB, Horizon, and GSK.