The currently pegylated uricase treatment for refractory gout is compromised by the development of anti-drug antibodies (ADAs) for most patients, adversely affecting efficacy and safety. We have developed synthetic nanoparticles encapsulating rapamycin (SVP-R) that are capable of inducing antigen-specific immunological tolerance to biologic drugs (Kishimoto et al., Nature Nanotech 2016). We report on initial data from a Phase 2 open label multidose clinical study of SEL-212, the combination of SVP-R and the pegylated uricase enzyme pegsiticase, in symptomatic gout patients with hyperuricemia. The primary and secondary endpoints for this trial include the safety, tolerability and pharmacokinetics of repeated monthly doses of SEL-212; sustained reduction of serum uric acid levels (sUA); and prevention of ADAs. As of March 23, 2017, a total of 38 patients had been dosed at 10 U.S. clinical sites. Five of six control patients administered 0.2 mg/kg or 0.4 mg/kg of pegsiticase alone were unable to maintain control of sUA for more than 14-21 days, as expected. In contrast, 11 of 13 patients administered 0.08 mg/kg of SVP-R + 0.2 mg/kg or 0.4 mg/kg of pegsiticase had thus far maintained control of sUA levels for up to 56 days and continue to be dosed. One patient in these cohorts was lost to a protocol deviation and the other reached the trial’s stopping rules for failure to control sUA levels. These data suggest that SVP-R can significantly enhance the activity of pegsiticase. Additional data will be updated at the time of presentation.
Chief Scientific Officer