Topical lacritin C-terminal peptide 'Lacripep^TM' significantly reduces both inferior corneal staining and burning/stinging in primary Sjögren's Syndrome dry eye

Abstract

Purpose : Lacritin is a human tear protein with preclinical basal tear and corneal epithelial restorative properties encapsulated in the potent C-terminal synthetic peptide 'Lacripep^TM' (also known as 'N-94/C-6'). Lacripep^TM and natural C-terminal Lacripep^TM-like tear fragments also stabilize the tear film by interacting with the meibum fatty acid 'OAHFA'. Lacritin and fragments are selectively deficient or absent in almost all dry eye tears, particularly those from primary Sjögren's Syndrome. Here we test topical Lacripep^TM at two concentrations versus placebo as a natural replacement therapy in primary Sjögren's Syndrome - the first in human trial.

Methods : A double-masked, randomized, thirty-five center, first-in-human phase 2 study to evaluate the efficacy and safety of 0.005% and 0.01% Lacripep™ in 204 subjects with dry eye associated with primary Sjögren's Syndrome was performed (ClinicalTrials.gov Identifier: NCT03226444) with both signs and symptoms assessed using NEI Workshop fluorescein corneal staining scoring and specific standardized patient symptomatology. Visit one initiated a two-week washout, followed by randomization at visit two, topical treatment TID for four weeks and a two-week washout. Endpoints were monitored after two and four weeks of treatment, and after treatment washout.

Results : After two weeks, 0.005% Lacripep™ demonstrated a -0.4 reduction in inferior corneal staining (p value vs placebo 0.0055) - that segment of the cornea recognized as the most relevant in dry eye disease, as well as a -14.5 point reduction in complaints of burning and stinging (p value vs placebo 0.0024). Lacripep™ was well tolerated and there were no serious treatment related adverse events. The results are consistent with a bell-shaped dose response (as seen in both preclinical and cell culture studies) and suggest the need for lower dose optimization.

Conclusions : Lacripep™ appears to be rapidly efficacious for both sign and symptom in primary Sjögren's syndrome, the most severe form of dry eye. This is the largest ophthalmic trial to date in primary Sjögren's Syndrome dry eye and was the first-in-human clinical study conducted with Lacripep™ as the active ingredient.

This is a 2021 ARVO Annual Meeting abstract.