Poster Session A
Crystal arthropathies
Herbert Baraf, MD, FACP, MACR
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Bethesda, MD, United States
Disclosure(s): Horizon Pharmaceuticals: Grant/Research Support (Ongoing), Speaker/Honoraria (includes speakers bureau, symposia, and expert witness) (Ongoing); Swedish Orphan Biovitrum (Sobi): Grant/Research Support (Ongoing), Speaker/Honoraria (includes speakers bureau, symposia, and expert witness) (Ongoing)
Background/Purpose: In patients with refractory gout, the inability to maintain serum uric acid (sUA) levels < 6 mg/dL leads to severe clinical manifestations for which uricase-based therapies can be highly effective, though also immunogenic.1 SEL-212 is a once-monthly, novel 2-component, uricase-based infusion therapy being investigated in patients with refractory gout. SEL-212 consists of an infusion of tolerogenic nanoparticles containing rapamycin (SEL-110) followed by pegadricase (SEL-037).2 DISSOLVE I and II (D1 and D2, respectively) evaluated the safety and efficacy of SEL-212 in adults with refractory gout.
Methods: D1 (US) and D2 (Global), were placebo-controlled, double-blind, randomized clinical trials that evaluated two dose levels of SEL-110 (0.15 mg/kg [high-dose] or 0.1 mg/kg [low-dose]) prior to SEL-037 (0.2 mg/kg) infusion. Participants were enrolled if they had ≥ 3 gout flares within 18 months prior to screening or ≥ 1 tophus or a current diagnosis of gouty arthritis, failed to normalize sUA and control symptoms with any xanthine oxidase inhibitor, and were not previously exposed to a pegylated uricase-based therapy. Participants were randomized 1:1:1 between the two doses of SEL-212 and placebo administered intravenously every 28 days for 6 treatments. D1 participants continued in a 6-month blinded extension phase under the initial treatment conditions (Fig. 1). The primary endpoint was defined as the percentage of participants who achieved and maintained sUA < 6 mg/dL for ≥ 80% of the sixth treatment period (TP6). Safety and tolerability were assessed through monitoring of adverse events (AEs).
Results: 112 participants (96% male, 66% ≥ 50 years) were enrolled in D1 and 153 (97% male, 72% ≥ 50 years) in D2. Response rates in all treatment groups were significantly different from placebo (p ≤ 0.0008), with 56% and 46% of participants responding in the high-dose group and 48% and 40% in the low-dose group for D1 and D2, respectively (Figure 2). The response rates in participants aged ≥ 50 years were 65% and 47% in the high-dose groups and 47% and 44% in the low-dose groups for D1 and D2, respectively (p ≤ 0.0026 vs placebo). Across all participants in the treatment groups, sUA levels were significantly reduced from baseline (p< 0.001 vs placebo) at TP6 (Figure 3). The safety profile of SEL-212 was favorable, with 3.4% and 4.5% of participants experiencing infusion reactions in the high and low-dose groups, respectively. Reports of gout flares were comparable between treatment groups and placebo. Six participants (3.4%) in the pooled active treatment groups experienced treatment-related serious AEs (n=4 anaphylaxis, n=2 gout flares).
Conclusion: In the DISSOLVE trials, once-monthly treatment with SEL-212 demonstrated statistically significant response rates and reductions in sUA versus placebo. The safety profile of SEL-212 was consistent with that of uricase therapies. Targeted immunomodulation with SEL-212 has the potential to provide a new uricase-based treatment option for patients with gout refractory to conventional therapies.
