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Reformulated rapamycin (sirolimus) shows promising 12-month results in treatment of uveitis

Results of a clinical trial into the treatment of non-infectious uveitis, supported by Santen Inc. (Osaka, Japan), have reported that over 70% of the patients receiving the study drug had a 2-step or greater reduction in vitreous haze at month 12 (P , 0.05).   The study, carried out by researchers at the Wilmer Eye Institute, Johns Hopkins University School of Medicine in Baltimore and referenced as “SAVE” (Sirolimus as a Therapeutic Approach UVEitis (SAVE), was designed to assess the efficacy and safety of repeated intravitreal and sub-conjunctival administration of sirolimus in patients with noninfectious uveitis.   The drug is currently approved for use in the prevention of kidney transplant rejection and for use in patients with ischemic heart disease to enhance coronary luminal diameter (eluted from a coronary stent).


Known as sirolimus, the small molecule was originally isolated in the 1970s from bacteria on Easter Island (Streptomyces hygroscopicus) and developed as an antifungal agent until it was shown to have both immunosuppressive and antiproliferative properties. Subsequent research demonstrated its potential in both reducing transplant rejection and as a potential anti-cancer therapy. However, cytotoxicity in ocular use led to re-formulation studies which recently demonstrated suitability in sub-conjunctival and intravitreal injection. Based on the anti-inflammatory effects of the drug, its application to uveitis patients was researched in the SAVE Study with patients randomized to receive either intravitreal or subconjunctival sirolimus. The study indicated that 80% of patients treated had significant improvement of the inflammatory indices (P, 0.05) in both study groups at 6 months. After this 6-month primary end point (if retreatment criteria were met) patients in either group were treated with sirolimus injections in the same dose and route of injection initially assigned during the active phase of the study. The follow-up period continued until month 12 and the results were published in the ARVO journal, Translational Vision Science & Technology.


Conducted as an open-label, prospective, randomized interventional clinical trial, 30 patients with noninfectious intermediate, posterior or panuveitis received sirolimus 352-μg intravitreally or 1320-μg subconjunctivally (1:1). According to the 12-month outcome results presented, 70% of patients with active uveitis at baseline showed greater than or equal to 2 steps reduction of vitreous haze (VH) at month 12 (P , 0.05); 88% of patients with inactive uveitis at baseline showed either no change or reduction of VH to no haze, and; 36% of all patients gained greater than or equal to one line of visual acuity (VA); 21% lost greater than or equal to 1 line and, 43% showed no change. At the end of 1 year, the authors reported no statistical differences in efficacy between intravitreal and subconjunctival groups. In concluding their study the US research group commented that, “the SAVE Study illustrates for the first time the application of local formulations of sirolimus in non-infectious intermediate, posterior, and panuveitis. Subconjunctival/Intravitreal sirolimus may help to control inflammation while offering better tolerability/safety profiles than systemic therapies, including immunosuppressants and corticosteroids.”