Background/Purpose:  Pegylated uricases are promising therapies for the treatment of severe chronic gout, but are limited by their immunogenicity.  We have previously shown that synthetic vaccine particles encapsulating rapamycin (SVP-R) co-administered with pegadricase (also known as pegsiticase) prevented the formation of ADAs in a dose-dependent manner.  A Phase 1 study of SEL-212, a novel combination product consisting of pegadricase and SVP-R, demonstrated sustained control of serum uric acid (sUA) for at least 30 days after a single dose. Here we report data on the safety, tolerability, and effects on sUA, ADAs, and gout flares of repeated monthly doses of SEL-212 in symptomatic gout patients treated with 0.125 or 0.15 mg/kg SVP-R in combination with 0.2 or 0.4 mg/kg pegadricase.

Methods:  Patients with symptomatic gout (≥1 tophus, gout flare within 6 months, and/or gouty arthropathy) and elevated sUA (sUA ≥6 mg/dL) were enrolled in SEL-212 treatment cohorts.  Patients reported here received three monthly doses of SEL-212 (0.2mg/kg or 0.4mg/kg pegadricase combined with 0.125 or 0.15 mg/kg SVP-R) followed by two monthly doses of pegadricase alone. Safety, tolerability, sUA, and ADAs were monitored, and clinical data were collected.

Results:  As of 1 June 2018, 143 patients had been dosed in the Phase 2 study. Approximately 81% of evaluable patients receiving 0.125 or 0.15 mg/kg SVP-R administered with either 0.2 or 0.4 mg/kg pegadricase maintained serum uric acid levels substantially below 6 mg/dl at week 12 after three monthly doses of SEL-212.  The sustained reduction of sUA correlated with low or no ADAs. SEL-212 was generally well tolerated and associated with a low rate of gout flare rates.  Thirty-three percent of evaluable patients treated with 0.125-0.15 mg/kg SVP-R, and only 27% of all current patients in the SEL-212 Phase 2 trial, experienced gout flares after initiation of first treatment with continued reduction of gout flare rates over months two through five. This low rate of gout flares appears to be in contrast with higher incidence of gout flares reported in clinical trials involving other urate lowering therapies.

Conclusion:  SEL-212 has been well-tolerated, showing substantially reduced immunogenicity, sustained control of sUA, and low rate of gout flares with repeated monthly dosing.