Breakthrough in patients with refractory gout: Novel 2-component infusion therapy controls serum urate levels

In the 2 similarly designed DISSOLVE I and DISSOLVE II trials, almost 50% of patients receiving infusions with a novel 2-drug combo were able to get their serum urate concentrations under control. With this agent, anti-drug antibody responses, usually limiting the use of uricase products, are hindered by nano-encapsulated rapamycin.

As Prof. Herbert SB Baraf (Center for Rheumatology and Bone Research, IL, USA) said during his presentation: “At the moment, there are hardly any options for gout patients with refractory disease.” Uricase-based therapy is recommended for gout patients who have failed to achieve uric acid-lowering targets, but anti-drug antibodies diminish their effectiveness, leading to high treatment failure rates [1].

In the phase 3 studies DISSOLVE I (NCT04513366) and DISSOLVE II (NCT04596540),  the efficacy and safety of SEL-212 as a potential new uricase-based therapy was assessed [2]. SEL-212 is a monthly 2-component infusion therapy: It consists of pegadricase that elicits a vigorous anti-drug antibody response, limiting its use as a monotherapy and SEL-110, tolerogenic nanoparticles containing rapamycin. SEL-110 is administered 30 minutes before pegadricase and has been demonstrated to inhibit anti-pegadricase antibodies. Patients with symptomatic or refractory gout were randomised to receive a high or a low dose of SEL-212 or placebo, every 28 days for a total of 6 treatments. The primary endpoint was the percentage of participants achieving serum uric acid levels <6 mg/dl for at least 80% of the sixth 28-day treatment period. “Stringent stopping rules were implemented to minimise the risk of infusion-related adverse events,” Prof. Baraf emphasised.

Included were 265 participants whose demographic characteristics were balanced for age, BMI, and sex, but racial imbalances existed in both studies. Gout severity was numerically greater in the 153 patients included in DISSOLVE II. The primary efficacy endpoint was met for both studies and doses. In the DISSOLVE I study, 58% of participants in the high-dose group (n=38) and 48% in the low-dose group (n=37) responded to treatment (P<0.0001). The corresponding numbers in the DISSOLVE II study were 46% in the high-dose group (P=0.0002 vs placebo) and 40% in the low-dose group (P=0.0008 vs placebo). Median change in serum uric acid levels indicates large reductions in at least half of the patients. Patients older than 50 years had similar response rates.

Treatment was relatively tolerable. The infusion reaction incidence was 3.4% in the combined high-dose groups.

Prof. Baraf concluded that SEL-212 may potentially provide a new once-monthly uricase-based treatment option for patients with refractory gout.

1. Fitzgerald JD, et al. Arthritis Care Res (Hoboken). 2020;72:744-60.
2. Baraf HSB, et al. Safety and efficacy of SEL-212 in patients with gout refractory to conventional treatment: outcomes from two randomised, double-blind, placebo-controlled, multicenter phase III studies. LB0002, EULAR 2023, 31 May–3 June, Milan, Italy.

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Posted on 8 June, 202317 August, 2023