Herbert S.B. Baraf (1, 2), Alan Kivitz (3), Sheldon Leung (4), Olu Folarin (4), Joanna Sobierska (5), Jacquie Christie (5), Anand Patel (6), Wesley DeHaan (4), Rehan Azeem (4), Peter Traber (4)
Affiliation(s):
1. The Center for Rheumatology and Bone Research, Wheaton, Maryland, USA;
2. The George Washington University School of Medicine and Health Sciences, Washington DC, USA;
3. Altoona Center for Clinical Research, Arthritis and Osteoporosis Center, Duncansville, USA;
4. Sobi, Waltham, MA, USA;
5. Sobi, Basel, Switzerland;
6. Conquest Research, Winter Park, FL, USA
Background: Sustained hyperuricemia may lead to severe clinical manifestations in gout refractory to conventional urate lowering therapy (ULT). Uricase-based therapies can be effective, although immunogenicity can reduce efficacy. SEL-212 is a novel, once-monthly, 2-component, uricase-based infusion therapy being investigated in patients with refractory gout. SEL-212 consists of sequential infusions of nanoparticles containing sirolimus (SEL-110), which provide tolerance to the subsequent infusion of pegadricase (SEL-037), a pegylated uricase.
Objective: DISSOLVE I and II (D1 and D2, respectively) evaluated the safety and efficacy of SEL-212 in adults with refractory gout.
Methods: D1 (US Study, 12 months) and D2 (Global Study, 6 months), 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 in adults (19-80 years). Participants with a history of symptomatic gout were enrolled if they had ≥ 3 gout flares within 18 months prior to screening or/ and ≥ 1 tophus or a current diagnosis of gouty arthritis, failed to normalize sUA and inadequate control of signs and symptoms with medically appropriate doses of oral ULT or had contraindications to such treatment, and were not previously exposed to a uricase-based therapy. Participants were randomized 1:1:1 between high and low dose SEL-212 and placebo administered intravenously every 28 days for 6 treatments. D1 participants were continued in a 6-month blinded extension phase under the initial treatment conditions. The primary endpoint was defined as the percentage of participants who achieved and maintained sUA < 6 mg/dL for ≥ 80% of the sixth 28-day treatment period (TP6) in the active treatment groups (response rate). Safety and tolerability were assessed through monitoring of adverse events (AEs) and laboratory testing.
Results: A total of 265 participants (D1, n=112 (96% male, 66% ≥ 50 years); D2, n=153 (97% male, 72% ≥ 50 years) were randomized and dosed into the three treatment arms. Response rates in both active treatment groups were significantly greater versus 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. 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, median sUA levels were reduced by ~97% and ~66% from baseline at TP6 for D1 and D2, respectively. 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 without the need for traditional immunosuppressants.
Adaptation from: Baraf HSB, Arthritis Rheumatol. 2023;75(suppl 9): abstract number 0246.
Funding: The DISSOLVE I and II (NCT04513366 and NCT04596540) studies were jointly funded by Sobi and Selecta BioSciences, Inc and this publication was funded by Sobi.
Author disclosures: Herbert S.B. Baraf Consultant: Sobi, Selecta BioSciences, Grünenthal and Olatec; Speakers bureau: Horizon Pharmaceuticals, Grant/research support from: Horizon Pharmaceuticals, Sobi; Alan Kivitz Consultant: Janssen, AbbVie, Gilead, Grünenthal, Chemocentryx, Coval, Fresenius Kabi, Genzyme, GSK, Horizon, Prime, Prometheus, Selecta, Synact, Takeda-Nimbus, UCB, XBiotech, and ECOR1; Speakers bureau: Eli Lilly, Flexion, AbbVie, Amgen, Sanofi - Regeneron, and GSK; Shareholder of: Pfizer, GSK, Gilead, Novartis, and Amgen; Anand Patel Speakers bureau: Lexicon Pharmaceuticals; Sheldon Leung Shareholder of: Selecta Biosciences , Employee of: Sobi , Olu Folarin Shareholder of: Selecta Biosciences, Employee of: Sobi, Joanna Sobierska Employee of: Sobi; Jacquie Christie Employee of: Sobi; Rehan Azeem Shareholder of: Selecta Biosciences, Employee of: Sobi; Wesley DeHaan Shareholder of: Selecta Biosciences, Employee of: Sobi; Peter G. Traber Shareholder of: Selecta Biosciences, Employee of: Sobi;