Abstract
Purpose :
Intraocular EPO concentrations have been shown to be elevated in eyes with DME (Lim and Han, 2011), and in preclinical studies, EPO over-expression in mouse models contributes to retinal vascular pathologies [IOVS 60(9):3664]. The purpose of this study was to evaluate the safety and efficacy of IVT LKA651 (anti-EPO Fab), administered as monotherapy or in combination with Lucentis, in patients with diabetic macular edema (DME).
Methods :
This study was a 3-arm, parallel group, randomized, patient- and investigator-masked trial planned in 90 patients with DME. Patients were enrolled into 1 of 3 arms: LKA651 (5mg) monotherapy, LKA651 (1mg) plus Lucentis combotherapy, and Lucentis monotherapy. Patients were dosed 3 times in 4-week intervals in the treatment phase and then followed up for an additional 12 weeks in a treatment free extension.
Results :
The baseline demographic and disease characteristics were generally well balanced between the treatment arms. Of the 91 treated patients, majority were male (64.8%), White (90.1%), and the mean (± SD) age was 62.2 (± 8.60) years. Positive safety and tolerability profile of LKA monotherapy and combotherapy, was observed. There was no significant difference in the incidence of patients with severe AEs amongst the treatment arms. Both LKA monotherapy and combotherapy arms showed BCVA gains from baseline. A 4.9 letter mean improvement was observed from baseline in the LKA arm, which was lower than the 7.6 letters observed in the Lucentis arm and 9.5 letters observed in the combotherapy arm. The difference in MMRM model based mean estimates (90% CI; p-value) in BCVA at Week 12 was –2.7 (−6.6, 1.3; 0.866) letters for LKA monotherapy vs Lucentis, and +2.0 (−1.9, 5.8; 0.198) letters for LKA/Lucentis combotherapy vs Lucentis. LKA combotherapy demonstrated reduction in CSFT from baseline but this was not superior to reduction observed in the Lucentis comparator arm.
Conclusions :
Anti-EPO is a novel mechanistic approach to the treatment of DME. Positive safety and tolerability was observed for IVT doses of LKA651 monotherapy or LKA651 dosed in combination with Lucentis® in patients with DME. Treatment with IVT LKA651 showed clinically meaningful efficacy data with improvement in BCVA and CSFT from baseline and a positive safety and tolerability profile.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.