SEL-212, a novel monthly infusion therapy, has shown promising results in improving patient-reported outcomes (PROs) for adults with refractory gout. Data presented at the American College of Rheumatology (ACR) Convergence 2024 from dual Phase 3 trials, DISSOLVE I and DISSOLVE II, indicate clinically meaningful improvements after just three doses, with further enhancements observed after six doses. These findings suggest a significant advancement in managing refractory gout, a condition where conventional urate-lowering therapies fail to normalize serum uric acid (sUA) levels and control symptoms.
The global prevalence of gout is estimated between 1% and 2%, with increasing rates potentially linked to aging populations, drug utilization, and lifestyle factors. Gout significantly reduces patients' quality of life due to elevated sUA levels, leading to acute and chronic inflammation. Current treatments often fall short in providing adequate relief for those with refractory gout, highlighting the need for more effective therapeutic options.
Study Design and Results
The DISSOLVE I and DISSOLVE II trials were randomized, double-blind, placebo-controlled Phase 3 studies. Patients enrolled had refractory gout, defined by the inability of oral urate-lowering therapies to normalize sUA levels and control symptoms. Participants received either high- or low-dose SEL-212 plus SEL-037 or placebo on Day 0 for six 28-day treatment periods. Patient-reported outcomes were assessed using the 36-item Short Form survey (SF-36), Health Assessment Questionnaire-Disability Index (HAQ-DI), and pain visual analog scale (VAS) at baseline, Day 0 of treatment period 4, and Day 28 of treatment period 6.
SEL-212, comprised of nanoparticles containing sirolimus (SEL-110) and pegadricase (SEL-037), is designed to lower sUA levels. The trials demonstrated significant improvements in response rates (sUA <6 mg/dL for ≥80% of treatment period 6) and mean sUA levels with SEL-212 compared to placebo in chronic refractory gout. A post hoc analysis evaluated the impact of the first three doses (F3D) or six doses (F6D) of SEL-212 on physical and mental ability, daily activities, and reported pain.
Impact on Quality of Life
Results showed a greater change from baseline in the SF-36 physical component summary score with low-dose SEL-212 (5.6) versus placebo in the F3D subgroup. Further improvement in SF-36 physical component scores was observed with low-dose SEL-212 (9.0) and high-dose SEL-212 (6.8) versus placebo in the F6D subgroup. The SF-36 mental component summary score also improved to a greater extent with low-dose (4.7) and high-dose (2.9) SEL-212 versus placebo (1.6) in the F3D subgroup. An improvement was also observed in the low-dose SEL-212 (4.2) versus placebo (2.9) in the F6D subgroup.
For the F3D subgroup, baseline change in HAQ-DI was refined with low-dose SEL-212 (–0.4) versus placebo (–0.1). In the F6D subgroup, baseline change in HAQ-DI was improved with low-dose SEL-212 (–0.4) and high-dose SEL-212 (–0.3) versus placebo (–0.2). Similar trends were observed for the pain VAS score, with improved outcomes in the F6D and FD3 subgroups.
Expert Commentary
According to the investigative team led by Vibeke Strand, MD, division of immunology and rheumatology, Stanford University, “SEL-212 improved clinical and health-related quality of life outcomes, including functional ability, mental health, and pain, in adults with refractory gout, which is likely reflective of improved urate lowering with this novel agent.” The study authors concluded that clinically meaningful changes in PROs were reported after three doses of SEL-212, with further improvements after three additional doses, indicating an incremental health-related quality of life benefit with prolonged treatment duration.
