POS0033 HEALTH-RELATED QUALITY OF LIFE (HRQOL) AND OTHER SECONDARY CLINICAL OUTCOMES IN ADULTS WITH GOUT REFRACTORY TO CONVENTIONAL THERAPY TREATED WITH SEL-212: POOLED 6-MONTH DATA FROM THE PHASE 3 DISSOLVE I &amp; II CLINICAL TRIALS
Authors: P. Khanna, A. Patel, A. Singhal, A. Kivitz, J. Sobierska, H. Santin-Janin, N. Kragh, R. Azeem, W. Dehaan, P. Traber, H. S. B. Baraf
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Sustained hyperuricaemia (serum uric acid [sUA] ≥6.8 mg/dL) can lead to the systemic deposition of monosodium urate (MSU) crystals in the body (including cartilage, joints and soft tissues) and results in tophus formation, painful gout flares, tender/swollen joints, and poor health-related quality of life (HRQoL).[1] Uricase-based therapies effectively lower sUA in patients with clinical manifestations of gout refractory to conventional sUA-lowering therapies; however their use is limited by immunogenicity-related efficacy reductions and infusion reactions. SEL-212 is a novel, once-monthly uricase-based therapy comprising sequential infusions of tolerogenic nanoparticles containing sirolimus (SEL-110) followed by a pegylated uricase (pegadricase; SEL-037). Co-administration of SEL-110 with SEL-037 provides targeted immunomodulation that mitigates uricase immunogenicity, thereby enabling sustained sUA control without the need for broader immunosuppression.[2] Six-month efficacy and safety data for SEL-212 have previously been reported in the phase 3 US and global DISSOLVE I &amp; II clinical trials.[3,4] <h3>Objectives:</h3> To report aggregated 6-month secondary clinical outcomes (including HRQoL) for SEL-212 in DISSOLVE I &amp; II. <h3>Methods:</h3> DISSOLVE I &amp; II are placebo-controlled, double-blind, randomised, replicate-design phase 3 clinical trials evaluating the safety/efficacy of once-monthly SEL-212 (SEL-110 0.15 mg/kg [high-dose, HD] or 0.1 mg/kg [low-dose, LD] with SEL-037 [0.2 mg/kg]) in adults with sUA ≥7 mg/dL and inadequate symptom control despite medically appropriate doses of conventional gout therapies. Prespecified pooled analyses of data from DISSOLVE I &amp; II evaluated secondary clinical outcomes, including changes<b></b>from baseline to treatment period (TP) 6 in health assessment scores (SF-36v2 physical component summary score and total HAQ-DI score), and tender joints. Changes in gout flare incidence were analysed for TP 1-3 and TP 4-6. <h3>Results:</h3> Overall, 87, 88, and 90 patients in the pooled intent-to-treat (ITT) set received HD, LD and placebo, respectively. Of these, 60, 60 and 70, respectively, (40, 39, and 68 on treatment) completed TP 6. Patients were predominantly white, male, had at least one tophus and an impaired HRQoL at baseline; characteristics were similar across treatment arms (<b>Table 1</b>). Least squares mean changes in SF-36 physical component summary score and total HAQ-DI score from baseline to TP 6 and differences in both outcomes for SEL-212 HD/LD versus placebo at TP 6 are shown in the <b>Figure 1</b>. The reduction in mean number of tender joints from baseline to TP 6 was numerically greater with HD and LD (5.3 and 6.7, respectively) versus placebo (2.7). Mean gout flare incidence was 0.3 for all three treatment arms during TP 1-3 and 0.1, 0.0, and 0.2 for HD, LD, and placebo, respectively, during TP 4-6. <h3>Conclusion:</h3> Aggregated data from DISSOLVE I &amp; II demonstrate improvements in HRQoL and tender joint count in patients with gout refractory to standard therapy treated with both doses of SEL-212. Similar gout flare incidence during the first three months and subsequent reductions in flare frequency by the end of the study indicate a decline in the body's burden of urate over time. <h3>REFERENCES:</h3> [1] Khanna P, et al. Journal of Clinical Medicine. 2020;9(10):3204. [2] Kivitz A, et al. Rheumatology and Therapy. 2023;10(4):825-847. [3] Baraf HSB, et al. Annals of the Rheumatic Diseases. 2023;82(suppl 1):200-201 (Abstract LB0002). [4] Baraf HSB, et al. Arthritis and Rheumatology. 2023;75(suppl 9): Abstract 0246. <h3>Acknowledgements:</h3> The DISSOLVE I (NCT04513366) and II (NCT04596540) trials were jointly funded by Sobi and Selecta BioSciences, Inc. This publication was funded by Sobi. <h3>Disclosure of Interests:</h3> Puja Khanna Horizon Pharmaceuticals, Sobi, Arthrosi, Olatec, Selecta BioSciences, Dyve Biosciences, Anand Patel Lexicon Pharmaceuticals, Atul Singhal: None declared, Alan Kivitz Eli Lilly, Flexion, AbbVie, Amgen, Sanofi-Regeneron, GSK, Prizer, GSK, Gilead, Novartis, Amgen, Janssen, AbbVie, Gilead, Grunenthal, Chemocentryx, Coval, Fresenius Kabi, Genzyme, GSK, Horizon Pharmaceuticals, Prime, Prometheus, Selecta, Synact, TAkeda-Nimbus, UCB, XBiotech, ECOR1, Joanna Sobierska Sobi, Hugues Santin-Janin Sobi, Nana Kragh Sobi, Rehan Azeem Selecta Biosciences, Sobi, Wesley DeHaan Selecta Biosciences, Sobi, Peter Traber Selecta Biosciences, Sobi, Herbert S.B. Baraf Horizon Pharmaceuticals, Sobi, Horizon Pharmaceuticals, Selecta BioSciences, Grunenthal, Fresenius Kabi, Olatec, Horizon Pharmaceuticals, Sobi.