Ongoing study evaluates sirolimus as therapeutic option for uveitis

An ongoing phase III, sham-controlled study is investigating intravitreal sirolimus 440 μg (Opsiria, Santen) for the treatment of active, non-infectious uveitis of the posterior segment.

Reviewed by Steven Yeh, MD

The phase III LUMINA study is under way assessing the efficacy and safety of intravitreal sirolimus 440 μg (Opsiria, Santen) administered every 2 months for the treatment of active, non-infectious uveitis of the posterior segment, according to Steven Yeh, MD. Launched in November 2018, the multicenter study plans to enroll 200 patients who are being randomly assigned into three arms (2:2:1) to receive:

• sirolimus 440 μg (experimental test arm),

• a sham procedure (control arm), or

• sirolimus at an undisclosed, fixed dose (within the range of 44 to 880 μg) (dummy arm) every 2 months.

After an initial 6-month, double-masked, controlled period, LUMINA will continue with a 6-month, single-arm, open-label period to allow further evaluation of the efficacy and safety of intravitreal sirolimus 440 μg every 2 months for a longer duration than is appropriate for treatment with placebo or sham injection, explained Dr. Yeh, the M. Louise Simpson Associate Professor of Ophthalmology; director of the Uveitis Service, Emory Eye Center, Atlanta, and an investigator in LUMINA.

Elimination of vitreous haze (VH; VH score of 0) at month 3 is being analyzed as the primary outcome measure. Key secondary outcome measures include VH score of 0 or 0.5+ at month 3 and month 5 and percentage of patients with corticosteroid tapering success with resolution (VH score of 0) at month 3 and month 5.

Unmet need

Dr. Yeh is pleased Santen is continuing to pursue the development of sirolimus for non-infectious posterior uveitis given the unmet need for local therapy that averts corticosteroid-related side effects.

“We have a number of medications that can be used to treat posterior uveitis either systemically or locally, including corticosteroids and other immunosuppressive therapies, but they all have varying degrees of side effects that can pose limitations to their use,” he said.

Sirolimus inhibits the activity of the mammalian target of rapamycin (mTOR) that plays a critical role in autoimmune-based inflammation, and thus has a unique mechanism of action for controlling uveitis, he noted.

“It demonstrated promising efficacy signals in the phase III SAKURA program with good tolerability,” Dr. Yeh said. “It also had an acceptable side effect profile as it caused minimal elevation of IOP and cataract development.”

LUMINA is an important trial because it is continuing to evaluate the evidence for the role of sirolimus, and it can potentially give us another medication to use for this challenging disease process, he added.

The LUMINA protocol is designed to study control of active disease. In contrast to the SAKURA program protocol that originally included two experimental test arms evaluating sirolimus doses of 440 and 880 μg and used sirolimus 44 μg for the control, LUMINA is evaluating only the 440 μg dose, and control patients are receiving a sham injection.

“In the SAKURA program, 440 μg sirolimus had the most favorable benefit:risk profile among the three doses studied,” he said. The dummy arm in LUMINA is interesting from a study design perspective and can provide valuable information.

The undisclosed, fixed dose (within the range of 44 μg to 880 μg) will be administered to patients in this arm and will be included in the study to help ensure masking of treatment assignments, he noted. The anticipated completion date of LUMINA is 2021. Thirty-five study sites are participating.

Disclosures:

Steven Yeh, MD
E: steven.yeh@gmail.com
Dr. Yeh is a consultant to Santen and Clearside Biomedical.