| الوصف: |
Background: Pegylated uricases are promising therapies for the treatment of severe chronic gout, but are limited by their immunogenicity. We have previously shown that ImmTOR tolerogenic nanoparticles (formerly known as SVP-Rapamycin) encapsulating rapamycin co-administered with pegadricase prevented the formation of anti-drug antibodies (ADAs) in a dose-dependent manner. A prior Phase 1b study of SEL-212, a novel combination product candidate consisting of pegadricase and ImmTOR, demonstrated sustained control of serum uric acid (SUA) for at least 30 days after a single dose. Here we provide data from a recently completed Phase 2 multidose clinical trial. Objectives: To assess data on the safety, tolerability, and effects on SUA, ADAs, and gout flares of five monthly doses of SEL-212 in symptomatic gout patients treated with 0.1 or 0.15 mg/kg ImmTOR in combination with 0.2 mg/kg pegadricase. Methods: Patients with symptomatic gout (≥1 tophus, gout flare within 6 months, and/or gouty arthropathy) and elevated SUA (≥6 mg/dL) were enrolled in SEL-212 treatment cohorts. Patients reported here received up to five monthly doses of SEL-212 (0.2 mg/kg pegadricase combined with 0.1 or 0.15 mg/kg ImmTOR). Safety, tolerability, SUA, and ADAs were monitored, and clinical data were collected. Results: As of 17 Dec 2018, 152 patients had been dosed in the Phase 2 study. All evaluable patients receiving 0.1 or 0.15 mg/kg ImmTOR administered with 0.2 mg/kg pegadricase who achieved three months of SUA control maintained SUA control in months four and five of combination treatment. Approximately 66% of evaluable patients maintained SUA levels below 6 mg/dL at week 20 after five 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. Only 35% of patients treated with five doses of 0.1-0.15 mg/kg ImmTOR, and 29% of all current patients in the SEL-212 Phase 2 trial, experienced gout flares after initiation during the first month of 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. SEL-212 has a favorable product profile to address the unmet need of patients with severe, chronic gout including low immunogenicity allowing continued dosing, lower reported flare rates and convenient monthly dosing. Disclosure of Interests: Stephen Smolinski Shareholder of: Selecta Biosciences, Inc., Employee of: Selecta Biosciences, Inc., Alan Kivitz Shareholder of: Novartis, Consultant for: Abbvie, Janssen, Pfizer, UCB, Genzyme, Sanofi, Regeneron, Boehringer Ingelheim, Sun Pharma Advanced Research, Flexion., Paid instructor for: Celgene, Horizon, Merck, Novartis, Pfizer, Genzyme, Sanofi, Regeneron, Speakers bureau: Celgene, Horizon, Merck and Genetech, Flexion, Wesley DeHaan Shareholder of: Selecta Biosciences, Inc., Employee of: Selecta Biosciences, Inc., Lloyd Johnston Shareholder of: Selecta Biosciences, Inc., Employee of: Selecta Biosciences, Inc., Rehan Azeem Shareholder of: Selecta Biosciences, Inc., Employee of: Selecta Biosciences, Inc., Kei Kishimoto Shareholder of: Selecta Biosciences, Inc., Employee of: Selecta Biosciences, Inc. |
