SEL-212 Advances Refractory Gout Outcomes with Prolonged Treatment

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Results of dual randomized Phase 3 trials identified improvement in patient-reported outcomes (PROs) after treatment with SEL-212, a novel, monthly, two-component infusion therapy, in adults with refractory gout.¹

These data, presented at the American College of Rheumatology (ACR) Convergence 2024, showed a clinically meaningful change in PROs after 3 doses of SEL-212, with further improvement after 3 additional doses, among adults with ≥3 gout flares within 18 months before screening, ≥1 tophus, or a current diagnosis of gouty arthritis.

“SEL-212 improved clinical and health-related quality of life outcomes, including functional ability, mental health, and pain, in adults with refractory gout, which is likely reflective of improved urate lowering with this novel agent,” wrote the investigative team, led by Vibeke Strand, MD, division of immunology and rheumatology, Stanford University.

Gout is the most common arthritis in adults, reporting a worldwide prevalence of 1 to 2%.² Factors, including population aging, increased drug utilization, and lifestyles and dietary habits, could play a role in these increasing rates. Individuals with gout experience reductions in quality of life, including health-related quality of life, owing to increasing serum uric acid (sUA) levels causing acute or chronic inflammation.

SEL-212, a two-component infusion therapy of nanoparticles containing sirolimus (SEL-110) and pegadricase (SEL-037), is designed to reduce sUA levels.¹ The DISSOLVE I and DISSOLVE II trials were randomized, double-blind, placebo-controlled Phase 3 trials of patients wherein oral urate-lowering therapy could not normalize sUA levels and control symptoms.

Enrolled individuals received high- or low-dose SEL-212 plus SEL-037 or placebo on Day 0 for 6 28-day treatment periods. PROs were assessed at baseline, Day 0 of treatment period 4, and Day 28 of treatment period 6, using the 36-item Short Form survey (SF-36), Health Assessment Questionnaire-Disability Index (HAQ-DI), and pain visual analog scale (VAS).

Data from DISSOLVE I and DISSOLVE II showed a significant improvement in response rates (sUA <6 mg/dL for ≥80% of treatment period 6) and mean sUA levels with SEL-212 versus placebo in chronic refractory gout. A post hoc analysis evaluated the first 3 (F3D) or 6 doses (F6D) in patients who received SEL-212, to further investigate the drug’s impact on physical and mental ability, daily activities, and reported pain.

Baseline characters remained well-balanced in the intent-to-treat and F3D and F6D populations and across treatment arms for each subgroup. Analysis revealed a greater change from baseline in the SF-36 physical component summary score with low-dose SEL-212 (5.6) versus placebo in the F3D subgroup.

Further improvement in the SF-36 physical component scores was observed with low-dose SEL-212 (9.0) and high-dose SEL-212 (6.8) versus placebo in the F6D subgroup. Change from baseline in the SF-36 mental component summary score was improved to a greater extent with low-dose (4.7) and high-dose (2.9) SEL-212 versus placebo (1.6) in the F3D subgroup. An improvement was also observed in the low-dose SEL-212 (4.2) versus placebo (2.9) in the F6D subgroup.

For the F3D subgroup, baseline change in HAQ-DI was refined with low-dose SEL-212 (–0.4) versus placebo (–0.1). In the F6D subgroup, baseline change in HAQ-DI was improved with low-dose SEL-212 (–0.4) and high-dose SEL-212 (–0.3) versus placebo (–0.2). Overall, Strand and colleagues identified similar data for the pain VAS score, with a trend for improved outcomes in the F6D and FD3 subgroups.

“Clinically meaningful changes in PROs were reported after 3 doses of SEL-212, which further improved after 3 additional doses, indicating patients reported an incremental HRQoL benefit with prolonged treatment duration,” Strand and colleagues wrote.

References

1. _{Strand V, Khanna P, Kivitz A, Kragh N, Falk A, Azeem R, Santin-Janin H, Baraf H. Improvements in Patient-Reported Outcomes After Treatment with SEL-212 in Adults with Refractory Gout: Results from Two Randomized Phase 3 Trials [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/improvements-in-patient-reported-outcomes-after-treatment-with-sel-212-in-adults-with-refractory-gout-results-from-two-randomized-phase-3-trials/. Accessed November 25, 2024.}
2. _{Scire CA, Manara M, Cimmino MA, Govoni M, Salaffi F, Punzi L, Monti MC, Carrara G, Montecucco C, Matucci-Cerinic M, Minisola G; KING Study Collaborators. Gout impacts on function and health-related quality of life beyond associated risk factors and medical conditions: results from the KING observational study of the Italian Society for Rheumatology (SIR). Arthritis Res Ther. 2013 Aug 23;15(5):R101. doi: 10.1186/ar4281. PMID: 24004577; PMCID: PMC3979095.}