POS0244 LONG-TERM IMPROVEMENTS IN SERUM URIC ACID LEVELS, GOUT SYMPTOMS, AND SAFETY UP TO 12-MONTHS WITH SEL-212 IN GOUT REFRACTORY TO CONVENTIONAL THERAPY: RESULTS FROM THE DISSOLVE I PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED CLINICAL TRIAL
Authors: A. Kivitz, A. Singhal, A. Patel, K. Ayesu, J. Sobierska, H. Santin-Janin, W. Dehaan, R. Azeem, P. Traber, H. S. B. Baraf
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> A subset of patients with gout are refractory to conventional uric-acid lowering therapy (ULT) leading to severe clinical manifestations. Uricase-based therapies can be effective, although immunogenicity may impair efficacy and increase the risk of infusion reactions. SEL-212 is a novel, once-monthly treatment of sequential infusions of immune-tolerising, sirolimus-containing nanoparticles (SEL-110) followed by a pegylated uricase (pegadricase, SEL-037). The DISSOLVE I US Study was a 6-month trial with a 6-month extension phase that evaluated the safety and efficacy of SEL-212 in adults with refractory gout (RG). Six-month data were presented previously.[1,2] <h3>Objectives:</h3> To describe the efficacy and safety of SEL-212 in DISSOLVE I, including the 6-month extension phase. <h3>Methods:</h3> DISSOLVE I was a placebo-controlled, double-blind, 1:1:1 randomised clinical trial with a 6-month double-blinded extension that evaluated once-monthly, sequential administration of SEL-110 at either 0.15 mg/kg [high-dose, HD] or 0.1 mg/kg [low-dose, LD] with SEL-037 (0.2 mg/kg) versus PLA in adults with RG. RG was defined as failure to normalise serum uric acid (sUA) and inadequate disease control despite oral ULT at medically-appropriate doses. Meeting the stopping rule: sUA &lt;2.0 mg/dL (1 h following the study treatment in treatment phase [TP]1), and sUA &gt;1.0 mg/dL (Day 21, TP1), or sUA &gt;6.0 mg/dL (Day 21, TP2, 3, 4, or 5) led to withdrawal. 12-month outcomes included sUA reduction, swollen joint count, and safety. Responders had sUA &lt;6 mg/dL for ≥80% of the time during the stated TP. <h3>Results:</h3> Of 38, 37, and 37 intent-to-treat (ITT) patients on HD, LD, and placebo, respectively, 27 in each SEL-212 arm and 26 in the placebo arm completed the first 6-months and entered the 6-month extension. Twenty-three, 19, and 22 patients in the HD, LD, and placebo arms, respectively, completed the extension phase (TP7-12). During TP1-6, 8/38 (21.1%), 15/37 (40.5%), and 1/37 (2.7%) in the HD, LD, and placebo arms, respectively, met the stopping rule. During TP7-12, 1 patient in each SEL-212 arm (3.7% in each arm) and 0 in the placebo arm met the stopping rule. Most patients were male, white and over half had tophi at baseline (<b>Table 1</b>). At TP6, 67% (97.5% CI: 0.43-0.85) and 59% (97.5% CI: 0.36-0.8) of patients in the extension evaluable set were responders in the HD and LD arms, respectively; while 48% (97.5% CI: 0.26-0.71) in both arms kept the response at TP12. Following the first SEL-212 treatment (TP1), mean sUA levels were reduced to 0.2 mg/dL in the HD and LD arms and were maintained &lt;6 mg/dL throughout the main study and extension. sUA levels remained &gt;6 mg/dL in the PLA arm. At baseline, the mean (standard deviation [SD]) number of swollen joints was 2.0 (4.3), 3.6 (7.5), and 1.0 (3.4) in the SEL-212 HD, LD, and placebo arms (ITT), respectively. Reductions from baseline in mean (SD) swollen joint count were observed at the end of the 6-month extension with reductions of −1.8 (4.1), −1.9 (4.0), and −0.5 (1.1), in the HD, LD, and placebo arms, respectively. No new safety signals were detected in the extension period; 7 patients had serious adverse events not related to study drug, including one fatal event (motor vehicle accident); there were no infusion reactions within 1 h of SEL-212 administration (serious or non-serious); and no serious gout flares. Over the whole study, 8 patients in active treatment arms had stomatitis, all were mild-to-moderate in severity. The most common adverse event of special interest across all three treatment arms was gout flare (<b>Table 2</b>). <h3>Conclusion:</h3> SEL-212 efficacy was maintained over the 12-month follow-up period and no new safety signals were observed, suggesting that investigational SEL-212 has the potential to be an effective therapy for patients with refractory gout. Once-monthly dosing, and the novel use of sirolimus-containing nanoparticles to mitigate against the development of anti-uricase immunity, differentiates SEL-212 from the currently-approved uricase therapy. <h3>REFERENCES:</h3> [1] Baraf HSB, et al. Annals of the Rheumatic Diseases 2023;82(suppl 1):200-201 (abstract LB0002). [2] Baraf HSB, et al. Arthritis Rheumatol. 2023;75(suppl 9): abstract number 0246. <h3>Acknowledgements:</h3> The DISSOLVE I (NCT04513366) study was jointly funded by Sobi and Selecta BioSciences, Inc and this publication was funded by Sobi. <h3>Disclosure of Interests:</h3> Alan Kivitz AbbVie, Amgen, Eli Lilly, Flexion, GSK, Sanofi-Regeneron, Amgen, GSK, Gilead, Novartis, Pfizer, AbbVie, Chemocentryx, Coval, ECOR1, Fresenius Kabi, Genzyme, Gilead, Grunenthal, GSK, Horizon Pharmaceuticals, Janssen, Prime, Prometheus, Selecta, Synact, Takeda-Nimbus, UCB, XBiotech, Atul Singhal: None declared, Anand Patel Lexicon Pharmaceuticals, Kwabena Ayesu: None declared, Joanna Sobierska Sobi, Hugues Santin-Janin Sobi, Wesley DeHaan Selecta Biosciences, Sobi, Rehan Azeem Selecta Biosciences, Sobi, Peter Traber Selecta Biosciences, Sobi, Herbert S.B. Baraf Horizon Pharmaceuticals, Fresenius Kabi, Grunenthal, Olatec, Selecta BioSciences, Sobi, Horizon Pharmaceuticals, Sobi.