Abstract
Purpose :
PCEDs result from the failure of rapid corneal re-epithelialization (re-epi) within 10-14 days after corneal insult, despite standard supportive treatment. NEXAGON® (lufepirsen ophthalmic gel) is an unmodified antisense oligonucleotide that restores ocular surface homeostasis by downregulating pathogenically elevated connexin 43 protein transcription, quelling unregulated inflammation associated with PCED. This multi-center study evaluates topical NEXAGON use in patients with PCEDs due to chemical/thermal injuries (CTI).
Methods :
Subjects meeting the eligibility criteria were randomized (1:1:1) to receive topical NEXAGON high dose (NEX-HD), NEXAGON low dose (NEX-LD) or NEXAGON Vehicle (VEH) in the study eye for up to 28 days (treatment period), prior to entering a 28-day follow-up. Corneal epithelial recovery (primary endpoint) was defined as corneas exhibiting (1) complete corneal re-epi within the treatment period, (2) that is maintained for ≥ 28 continuous days post re-epi (re-epi + durability). Additional data collected included overall safety, visual acuity changes, and time to re-epi. An analysis of the data was performed once 35 subjects of a planned 108 were enrolled and had completed the study.
Results :
Subjects with ages ranging from 7 to 75 years had a mean baseline corneal defect area of 46.67 mm2 (4 to 176 mm2). Treatment was well tolerated, with most TEAEs across all 3 treatments similarly characterized as mild/moderate and unlikely/unrelated to study drug. Treatment was discontinued in 4 subjects, 3 due to AEs (not study drug related), 1 in each treatment group. One SAE deemed not related to study drug was reported. When the primary endpoint was assessed, subjects in the NEX-HD (n=12) and NEX-LD (n=12) treatment groups achieved 66.7% corneal epithelial recovery, as compared to 27.3% of those receiving Vehicle (n=11), a clinically meaningful difference of 39.4% (Fisher’s exact test: p=0.065: 95%CI (0.015, 0.674)).
Conclusions :
These preliminary observations corroborate NEXAGON’s previously demonstrated safety profile, establish clinical proof of concept for its unique mechanism and confirm further clinical evaluation is warranted to verify NEXAGON’s potential role in the therapeutic management of PCED, regardless of etiology.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.