Efficacy and Safety of Nanoencapsulated Sirolimus Plus Pegadricase: Results From the Randomized, Placebo-Controlled Phase 3 Trials.

OBJECTIVE

DISSOLVE I and II examined the efficacy and safety of nanoencapsulated sirolimus (NAS) plus pegadricase (NASP) in patients with uncontrolled gout (UG).

METHODS

In these double-blind, placebo-controlled Phase 3 trials of NASP, patients were randomized 1:1:1 to infusions of high-dose (HD) or low-dose (LD) NAS plus pegadricase (HD NASP, LD NASP, respectively) or placebo, given every 4 weeks for 6 doses. The primary endpoint was proportion of patients with serum urate (SU) < 6 mg/dL for ≥ 80% of the time during Weeks 21-24. Secondary endpoints included health-related quality of life, tophus resolution, tender joints, and gout flares. Safety was also assessed.

RESULTS

Overall, 265 patients received HD NASP, LD NASP, or placebo. SU response during weeks 21 to 24 was significantly higher with NASP than with placebo (HD NASP: 51%; LD NASP: 43%; placebo: 8%; P < 0.0001 for both doses vs placebo). Common adverse events included gout flares (HD NASP: 42.5%; LD NASP: 44.3%; placebo: 43.3%), infections (HD NASP: 23.0%; LD NASP: 18.2%; placebo: 16.7%), and stomatitis (HD NASP: 9.2%; LD NASP: 3.4%; placebo: 0%). Infusion reactions within 1 hour were infrequent (4%) in NASP-treated patients. During weeks 1 to 12, the proportion of patients with flares was similar between NASP- and placebo-treated patients; thereafter, it decreased in NASP-treated patients but remained unchanged with those receiving the placebo.

CONCLUSION

NASP treatment resulted in a significantly higher proportion of patients with complete SU response during weeks 21 to 24 compared with placebo and was generally well tolerated. NASP, an every-4-week treatment, can markedly alleviate disease burden in patients with UG.