SEL-212 Significantly Reduces Serum Uric Acid Levels in Patients With Gout

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Response rates in the DISSOLVE I and DISSOLVE II high-dose and low-dose groups receiving SEL-212 were significantly different from the placebo group.

Once-monthly treatment with SEL-212 exhibited statistically significant response rates and reductions in serum uric acid (sUA) levels compared with placebo in patients with refractory gout, according to data from the DISSOLVE I and DISSOLVE II trials presented at the European Congress of Rheumatology (EULAR) 2023.1 The safety profile of the drug was also consistent with uricase therapies.

Investigators believe these findings indicate the potential to provide a new uricase-based treatment option for patients with gout refractory to conventional therapies without the need for traditional immunosuppressants.

“Despite availability of effective therapies for gout, a small proportion of patients suffer from refractory gout and/or are intolerant to standard therapies,” wrote Herbert S B Baraf, MD, associated with The Center for Rheumatology and Bone Research, Rheumatology, Wheaton, MA, and colleagues. “In these patients, the inability to maintain sUA levels < 6 mg/dL may lead to severe clinical manifestations for which uricase-based therapies can be highly effective, though also immunogenic.”

SEL-212 is a once-monthly, novel 2-component, sequential uricase-based infusion therapy consisting of a combination infusion of tolerogenic nanoparticles containing rapamycin (SEL-110) and subsequential pegadricase (SEL-037). The combination is designed to inhibit the formation of anti-uricase antibodies without the need for other immunosuppressant therapies.2

The DISSOLVE I (United States-based, 12 months) and DISSOLVE II (global study, 6 months) studies were placebo-controlled, double-blind, randomized clinical trials that assessed 2 dose levels of SEL-110 (0.15 mg/kg [high-dose] or 0.1 mg/kg [low-dose]) before the SEL-037 (0.2 mg/kg) infusion in adult patients, aged 19 to 80 years. Eligible patients had a history of symptomatic gout and experienced ≥3 gout flares within 18 months prior to screening or ≥1 tophus or a current diagnosis of gouty arthritis, had failed to normalize sUA and control symptoms with any xanthine oxidase inhibitor, and did not have previous exposure to a uricase-based therapy.

Patients were randomized to receive either the 2 doses of SEL-212 or placebo, administered intravenously every 28 days for 6 treatments, or placebo. Patients in DISSOLVE I were enrolled in a 6-month blinded extension phase using the initial treatment conditions.

The primary endpoint was the percentage of participants who were able to achieve and maintain sUA <6 mg/dL for ≥ 80% during the sixth 28-day treatment period in the active treatment group compared with placebo (response rate). Adverse events and laboratory testing evaluated safety and tolerability.

In total, 265 participants (DISSOLVE I: n = 112; DISSOLVE II: n = 153) were randomized 1:1:1 into the treatment arms. Most patients were male (96% and 97%, respectively) and aged ≥50 years (66% and 72%, respectively).

Response rates in the DISSOLVE I and DISSOLVE II high-dose group were 56% and 47%, respectively. The low-dose group response rates were 48% and 41%, respectively. These rates were significantly different from the placebo group (P ≤.0015).

Response rates in patients ≥50 years were 65% and 48% in the high-dose groups and 47% and 45% in the low-dose groups for DISSOLVE I and DISSOLVE II, respectively (P ≤.0044 vs placebo). Median sUA levels were reduced by ~96% and ~75% from baseline in both trials, respectively (P <.001 vs placebo). Additionally, the safety profile was favorable, with 3.4% and 4.5% of participants reporting infusion reactions in the high- and low-dose groups, respectively.

Gout flares were similar among both treatment groups and placebo and 6 (n = 3.4%) of participants in the pooled treated groups reported treatment-related serious adverse events, including anaphylaxis (n = 4) and gout flares (n = 2).


  1. H S B Baraf, A Kivitz, S Rhodes, S Leung, et al. Safety & Effiicacy of SEL-212 in Patients With Gout Refractory to Conventional Treatment: Outcomes From Two Randomized, Double Blind, Placebo-Controlled, Multicenter Phase III Studies. Paper presented at: European Congress of Rheumatology (EULAR) 2023. Milan, Italy. May 31 – June 3, 2023.
  2. Sands, E., Kivitz, A., DeHaan, W. et al. Tolerogenic nanoparticles mitigate the formation of anti-drug antibodies against pegylated uricase in patients with hyperuricemia. Nat Commun 13, 272 (2022).