Session Title: Free Paper Session 10: Uveitis
Session Date/Time: Friday 08/09/2017 | 11:00-12:30
Paper Time: 11:00
Venue: Room 111
First Author: : C.Pavesio UK
Co Author(s): :
The SAKURA Program assessed the safety and efficacy of every-other-month intravitreal (IVT) sirolimus for the treatment of active non-infectious uveitis of the posterior segment (NIU-PS).
The SAKURA Program consisted of two Phase III (one pivotal, one supportive), randomized, multinational, active control studies that enrolled subjects from 134 sites in the USA, India, Europe, the Middle East and Africa, Latin America, and Japan.
Subjects were enrolled in SAKURA 1 (n=347) and SAKURA 2 (n=245) with vitreous haze (VH) ≥1.5+ in the study eye at baseline. Subjects from both studies comprised the integrated Intent-to-Treat (ITT) population evaluating IVT sirolimus 440 μg vs 44 μg active control, n=208 for each group. 80% of subjects (n=171 in 440 μg; n=163 in 44 μg) had multiple markers of inflammation (MMI) at baseline, defined as VH ≥1.5+ and ≥1 of the following characteristics of inflammation: requirement for systemic corticosteroids at an overall prednisone-equivalent dose ≥7.5 mg/day, best-corrected visual acuity ≤75 ETDRS letters, presence of macular edema (ME, central retinal thickness ≥300 µm on optical coherence tomography). The primary endpoint was the proportion of patients with VH score of 0 at Month 5. Change in CRT was also assessed at Month 5 and safety up to Month 6.
In the integrated ITT population (n=208 in each dose group), 21.2% vs 13.5% of subjects (in 440 µg vs 44 µg, p=0.0381) achieved the primary endpoint of VH=0 at Month 5. In the integrated subpopulation of subjects with MMI at baseline, 21.1% vs 8.0% (in 440 µg vs 44 µg, p=0.0007) achieved VH=0 at Month 5. In the integrated ITT population, 68 subjects in the 440 μg and 65 in the 44 μg groups had ME at baseline (mean CRT 501.65 μm and 507.89 μm, respectively). Among these subjects, 19.1% in the 440 μg and 12.3% in the 44 μg group achieved VH=0 at Month 5 (p=0.2816). Month 5 CRT data were available for 57 and 56 subjects in the 440 and 44 μg groups, respectively. The median percent change from baseline CRT was -23.7% in the 440 μg and -16.1% in the 44 μg group. The median change from baseline CRT was -102.5 microns and -72.5 microns in the 440 µg and 44 µg groups, respectively. Occurrences of serious ocular adverse events were similar among treatment groups, and no unexpected events were reported.
Efficacy results from the integrated analysis of the SAKURA Program demonstrated that the novel mTOR inhibitor IVT sirolimus, administered locally in a dose of 440 μg every other month, achieved statistically significant improvements in VH at Month 5 in subjects with active NIU-PS, including those subjects with MMI at baseline, when compared to 44 μg. The SAKURA Program, the largest study of NIU-PS to date, suggests IVT sirolimus 440 μg has the potential to reduce CRT in subjects with baseline ME and has a favorable benefit:risk profile over 44 µg.