SEL-212 Demonstrates Clinical Safety, Efficacy in Gout

Herbert Baraf, MD

Credit: National Institutute of Arthritis and Musculoskeletal and Skin Diseases

Both SEL-110 high dose (HD, 0.15 mg/kg) or low dose (LD, 0.1 mg/kg) with concomitant SEL-037 (0.2 mg/kg), known as SEL-212, demonstrated clinical efficacy and safety among a cohort of patients with gout refractory to standard treatment, according to data presented at the 2024 European Congress of Rheumatology (EULAR).¹ As a lower proportion of patients in the HD group met the stopping rule compared with the LD group, results indicated the higher dose may be more effective.

“In gout refractory to conventional uric acid lowering therapy (ULT), sustained hyperuricemia increases the risk of painful flares, chronic gouty arthropathy, and tophi,” wrote a team of investigators led by Herbert Baraf, MD, clinical professor of Medicine at George Washington University. “Uricase-based therapy can effectively reverse these outcomes but is limited by immunogenicity, which impairs efficacy and compounds the risk of infusion reactions.”

The novel, once-monthly therapy, SEL-212, consists of infusions of immune-tolerizing nanoparticles that contain sirolimus (SEL-110), given in either HD or LD formulations, followed by a dose of pegylated uricase (SEL-037) for 6 treatment periods (TP).

Data from the 6-month, placebo-controlled, double-blind, randomized DISSOLVE I and DISSOLVE II clinical trials were used to analyze the safety and efficacy of SEL-212 among this patient population. Refractory gout was defined as failure to normalize serum uric acid (sUA) coupled with inadequate control of symptoms despite receiving medically appropriate doses of an oral ULT. The primary endpoint was response rate, defined as sUA levels < 6 mg/dL for ≥ 80% of the time during TP6.

The stopping rule was defined as sUA < 2.0 mg/dL (1-hour post-treatment in TP1) and sUA > 1.0 mg/dL (Day 21, TP1), or sUA > 6.0 mg/dL (Day 21, TP2, 3, 4, or 5). Analyses of outcomes included sUA reduction, sUA responses, and safety.

Within the intent-to-treat population, 87 patients were placed in the HD arm, 88 in the LD arm, and 90 patients received placebo. Forty, 60, and 70 patients, respectively, completed the treatment phase. Approximately half (46%, n = 122/265) of pooled analysis patients discontinued treatment during the trial, with 43.2% (n = 38/88) in the LD cohort and 23.0% (n = 20/87) in the HD cohort meeting the stopping rule. Additional reasons for discontinuing treatment across all arms were withdrawal of consent and adverse events. Baseline characteristics were comparable across treatment groups.

The primary endpoint was met by 51% of patients in the HD group and 43% of patients in the LD group, compared with only 8% of those receiving placebo (P <.0001). Among patients with tophi at baseline, SEL-212’s risk ratio (RR) was significantly higher in the treatment groups (HD: 41%; LD: 43%) compared with placebo (9%; P = .0003 and .0002, respectively). Mean absolute sUA reductions from baseline were 5.3 mg/dL (60.8%) in the HD group, 4.5 mg/dL (52.2%) in the LD group, compared with only .3 mg/dL (2.1%) in the placebo group (P <.001).

Although most patients (72.4%, 70.5%, and 63.3% in the HD, LD, and placebo cohorts, respectively) reported at least 1 treatment-emergent adverse event (TEAE), most were categorized as mild or moderate in severity. The only TEAEs to affect ≥ 5% in both treatment arms were gout flares, COVID-19 infections, infusion-related reactions, and rash.

The most common TEAE was gout flare with 42.5% (n = 37) in the HD group, 44.3% (n = 39) in the LD group, and 43.3% (n = 39) in the placebo arm reporting a flare. Infusion-related adverse events were reported in 4.5% (n = 4) in the LD group, 3.4% (n = 3) in the HD group and 0% in the placebo group. No TEAEs resulted in the death of a patient. Other mild to moderate combined adverse events were stomatitis, oral ulcer, and aphthous ulcers; however, these did not lead to any withdrawals.

“Investigational once-monthly SEL-212 could be a well-tolerated and effective uricase-based urate-lowering therapy in patients with refractory gout,” concluded investigators.

References

1. ^{Baraf HSB, Khanna P, Patel A, Singhal A, et al. Once-Monthly SEL-212 Demonstrates Efficacy and Safety for up to 6-Months in Gout Refractory to Conventional Therapy: Combined Data From the DISSOLVE I & II Phase 3, Double-Blind, Placebo-Controlled Clinical Trials. Presented at: EULAR. Vienna, Austria. June 12 – 15, 2024.}