The COMPARE head-to-head, randomised-controlled trial of SEL-212 (pegadricase plus rapamycin-containing nanoparticle, ImmTOR™) versus pegloticase for refractory gout

Document Type

Journal Article

Publication Date

7-14-2023

Journal

Rheumatology (Oxford, England)

DOI

10.1093/rheumatology/kead333

Keywords

SEL-212; gout; nanotechnology; pegadricase; pegloticase; rapamycin; serum urate; uricase

Abstract

OBJECTIVES: Serum urate (SU) lowering with PEGylated uricases in gout can reduce flares and tophi. However, treatment-emergent anti-drug antibodies adversely affect safety and efficacy, and the currently-approved PEGylated uricase pegloticase requires twice-monthly infusions. Investigational SEL-212 therapy aims to promote uricase-specific tolerance, via monthly sequential-infusions of a proprietary rapamycin-containing nanoparticle (ImmTOR™) and pegadricase. METHODS: COMPARE was a randomised, Phase 2, open-label trial of SEL-212 vs pegloticase in adults with refractory gout. SEL-212 (ImmTOR™ [0.15 mg/kg] and pegadricase [0.2 mg/kg]) was infused monthly or pegloticase [8 mg] twice-monthly for 6 months. Primary end point: proportion of participants with SU < 6 mg/dl for ≥80% of the time during 3 and 6 months. Secondary outcomes: mean SU, gout flares, number of tender and/or swollen joints, and safety. RESULTS: During months 3/6 combined, numerically more participants achieved and maintained SU < 6 mg/dl for ≥80% of the time with SEL-212 vs pegloticase (53.0% vs 46.0%, p= 0.181). Percentage reductions in SU levels were statistically greater during months 3 and 6 with SEL-212 vs pegloticase (-73.79% and -47.96%, p= 0.0161). Reductions in gout-flare incidence and number of tender and/or swollen joints were comparable between treatments. There were numerical differences between the most common treatment-related adverse events of interest with SEL-212 and pegloticase: gout flares (60.2% vs 50.6%), infections (25.3% vs 18.4%), and infusion-related reactions (15.7% vs 11.5%), respectively. Stomatitis (and related terms) was experienced by 8 participants (9.6%) with SEL-212 and 0 with pegloticase. Stomatitis, a known event for rapamycin, was associated with ImmTOR™ only. CONCLUSIONS: SEL-212 efficacy and tolerability were comparable to pegloticase in refractory gout. This was associated with substantial reduction in treatment burden with SEL-212, due to decreased infusion frequency vs pegloticase. CLINICAL TRIAL REGISTRATION: NCT03905512.

Department

Medicine

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