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

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.

Herbert S B Baraf, MD

Credit: National Institute of Arthritis and Musculoskeletal and Skin Diseases

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).

References

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). https://doi.org/10.1038/s41467-021-27945-7}