Topline results from prospective, double-masked, placebo controlled phase 2b clinical study evaluating Luminate^® in patients with diabetic macular edema

Abstract

Purpose : Luminate^® is an RGD class synthetic anti-integrin oligopeptide. Studies have shown that it inhibits integrin receptors in vitro and arrests aberrant blood vessel growth in vivo meditated by αvβ3, αvβ5 as well as α2β1 and α5β1 - integrin sites that are expressed in neovascular ocular tissue from patients with diabetic retinopathy. A more recent Phase 1 study demonstrated its safety when injected intravitreally in human subjects with diabetic macular edema (DME). The purpose of this Phase 2b study was to investigate the safety and efficacy of Luminate, as compared to Avastin^® (bevacizumab), administered intravitreally in patients with DME.

Methods : 136 patients from 32 U.S. sites were randomly assigned to four groups. Groups received 1.0 mg, 2.0 mg, or 3.0 mg of Luminate, or 1.25 mg of Avastin. The Luminate groups received 3 monthly intravitreal injections (week 0, 4, and 8) while the Avastin group received up to 6 monthly injections (week 0, 4, 8, 12, 16, 20). The efficacy outcomes were change (from baseline) in BCVA and central macular thickness (CMT) at week 20. The safety outcomes were adverse events.

Results : At study week 20, continuous monthly Avastin was compared to 12 weeks post loading with Luminate. The mean (SD) change in BCVA were 5.2(6.86), 2.7(7.31), -1.5(9.97) and 7.0(8.21) letters gained in 1.0 mg, 2.0 mg and 3.0 mg Luminate versus 1.25 mg Avastin, respectively. The mean (SD) change in CMT were -77(141), -16(110), -1(152) and -104(107)μm, respectively. There were no drug related serious adverse events in the Luminate groups.

Conclusions : Data from this Phase 2b DME trial demonstrated that Luminate met its primary and secondary endpoints of BCVA and CMT change at study week 20. Three doses of Luminate demonstrated non-inferiority to 6 doses of Avastin (≤3 letters difference in BCVA and ≤30mm difference in CMT) at the primary endpoint of 20 weeks. Moreover, Luminate showed 12 week durability from the last dose in monotherapy use. Consistent with prior animal work, Luminate appears to have a U-shaped dose response curve with decreasing efficacy with increasing dosing above 1.0 mg Luminate.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.