Abstract
Purpose :
The SAKURA Program – two Phase III, multinational, multicenter, randomized, double-masked studies – assessed the safety and efficacy of every-other-month intravitreal (IVT) sirolimus for treating active non-infectious uveitis of the posterior segment (NIU-PS).
Methods :
SAKURA Study 1 enrolled subjects through March 31, 2013 (N=347) and SAKURA Study 2 enrolled subjects on/after April 1, 2013 (N=245). All subjects had vitreous haze (VH) ≥1.5+ at baseline. Subjects from both studies comprised the integrated Intent-to-Treat (ITT) population evaluating sirolimus 440 μg vs 44 μg active control, n=208 for each group. 81% of subjects in the SAKURA Program (n=171, 440 μg; n=163, 44 μg) were considered to have more severe disease at baseline, defined as VH ≥1.5+ and ≥1 markers of disease: systemic corticosteroids at an overall prednisone-equivalent dose >5 mg/day, best-corrected visual acuity ≤75 ETDRS letters, macular edema (central retinal thickness ≥300 µm on optical coherence tomography). VH was analyzed at Month 5 and safety at Month 6.
Results :
Study 1 demonstrated the efficacy of every-other-month IVT injections of 440 μg sirolimus over 44 µg. Although the results of Study 2 were not statistically significant (Figure), in the integrated ITT population, 21.2% and 13.5% of subjects (in 440 µg and 44 µg, p=0.0381) achieved the primary endpoint of VH=0 and 50% and 40.4% (in 440 µg and 44 µg, p=0.0488) achieved the pre-specified key secondary endpoint of VH score of 0 or 0.5+. In the integrated subpopulation of subjects with more severe disease, 21.1% and 8% of subjects (in 440 µg and 44 µg, p=0.0007) achieved VH=0 and 48% and 37.4% (in 440 µg and 44 µg, p=0.0519) achieved VH 0 or 0.5+. Occurrences of serious adverse events were similar among treatment groups in both the integrated ITT population and more severe disease subpopulation.
Conclusions :
The integrated analysis of the SAKURA Program demonstrated the efficacy and safety of the 440 μg dose of every-other-month IVT sirolimus in NIU-PS, including in those subjects with more severe disease.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.