P109 Clinical development of a novel strategy to mitigate biologic immunogenicity: monthly dosing of a pegylated uricase with SVP-R enables sustained reduction of serum uric acid (SUA) levels by mitigating formation of anti-drug antibodies (ADAS)
Authors: E Sands, A Kivitz, W DeHaan, L Johnston, TK Kishimoto
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Pegylated uricases are a promising but highly immunogenic therapy for severe gout. Preclinical studies have shown the ability of synthetic vaccine particles containing rapamycin (SVP-R) to inhibit the formation of ADAs against pegsiticase, a pegylated uricase.<sup>1</sup> Here we report initial data on the safety, immunogenicity and activity of an ongoing Phase 2 study of SEL-212, a novel combination therapy consisting of pegsiticase and SVP-R. <h3>Objectives</h3> Evaluate the ability of monthly doses of SEL-212 to mitigate the immunogenicity of pegsiticase and enable sustained control of sUA in gout patients. <h3>Methods</h3> Patients with symptomatic gout and elevated sUA (≥6 mg/dL) were treated with fixed doses of pegsiticase (0.2 mg/kg or 0.4 mg/kg) alone or co-administered with SVP-R (0.05, 0.08, or 0.1 mg/kg). SEL-212 was infused in 28 day cycles x3 doses followed by challenge with pegsiticase alone on 28 day cycles x2 doses. Safety, tolerability, sUA, and ADAs were monitored <h3>Results</h3> In the SEL-212 Phase 1b study, 70% of patients administered 0.4 mg/kg pegsiticase with a mid-dose of 0.1 mg/kg SVP-R showed low or no ADA formation correlating with sustained low sUA levels for at least 30 days after a single dose, compared to 20% for patients treated with pegsiticase alone. In the ongoing Phase 2 study, the majority of patients receiving 0.1 mg/kg SVP-R administered with either 0.2 or 0.4 mg/kg pegsiticase also showed low or no ADAs and maintained low sUA levels after 3 monthly doses of SEL-212, indicating sustained activity with repeated doses of SEL-212. However after 2 subsequent doses of pegsiticase alone, a drop in activity was noted. These data suggest that either a higher dose of SVP-R or the addition of SVP-R at the 4th and 5th dose may be required to sustain activity through 5 months. Currently patients are being dosed with 0.15 mg/kg SVP-R, a dose level which enabled sustained control of sUA levels in all patients in Phase 1b. SEL-212 was generally well tolerated and associated with a low rate of gout flare rates compared to those treated with pegsiticase alone. <h3>Conclusions</h3> SVP-R showed a dose-dependent reduction in ADAs and enabled sustained control of sUA with repeated dosing of SEL-212. SVP-R is a promising approach to prevent the formation of ADAs against immunogenic biologic therapies. <h3>Reference</h3> . Kishimoto TK, et al. <i>Nature Nanotechnol</i>2016;11:890–899. <h3>Acknowledgements</h3> We thank the patients that participated in these studies, the clinical study site investigators, and the entire SEL-212 project team. <h3>Disclosure of interest</h3> E. Sands Employee of: Selecta Biosciences, A. Kivitz: None declared, W. DeHaan Employee of: Selecta Biosciences, L. Johnston Employee of: Selecta Biosciences, T. Kishimoto Employee of: Selecta Biosciences