Melanocortin agonist PL9643 significantly improves ocular signs and symptoms of moderate to severe dry eye disease (DED), including tear film break up time (TFBUT)

Abstract

Purpose : DED is characterized by ocular irritation and potential visual impairment due to inflammation and tear deficiency. Melanocortin agonists may represent a new therapeutic avenue to treat inflammatory ocular diseases. The efficacy and tolerability of the melanocortin receptor pan-agonist PL9643 was examined in a subpopulation of subjects with moderate to severe DED as part of a phase 2 study.

Methods : This was a randomized, placebo-controlled study of subjects with DED. A subpopulation of subjects (n=53) with a duration of DED≥5 years, inferior corneal staining>1, and eye discomfort on a visual analog scale (VAS)≥25 was analyzed. Subjects received placebo solution during a 2-week run-in period and were randomized to either placebo or PL9643 topical solution TID for 12 weeks. The controlled adverse environment (CAE™) model was used to exacerbate signs/symptoms. Endpoints included TFBUT, changes in inferior corneal fluorescein staining and ocular discomfort (Ora Calibra^® scales) after 2 and 12 weeks. Other endpoints were changes in additional signs/symptoms of DED, and occurrence of adverse events (AEs).

Results : In these subjects with moderate or severe disease (n=53), PL9643 treatment demonstrated a significant improvement over placebo at week 12 for TFBUT with an LS means treatment difference vs placebo of +0.4058 (P=0.0137). PL9643 treatment also demonstrated a significant improvement over placebo for fluorescein staining with treatment differences of -0.55 (P=0.0097) for inferior corneal staining and -0.93 (P=0.0242) for corneal sum staining (inferior, superior, and central). Ocular discomfort demonstrated significant improvement vs placebo in change from baseline at week 2 (treatment difference -0.4, P=0.0227). In addition, PL9643 treatment demonstrated numerical improvement in conjunctival redness (Ora Calibra^® scale) and in VAS symptoms at weeks 2 and 12. Fewer AEs occurred in those receiving PL9643 vs placebo and there were no treatment-related serious or ocular AEs observed.

Conclusions : In subjects with moderate or severe DED, PL9643 led to significant improvement in TFBUT at week 12 and other subjective and objective benefits at 2 weeks which were maintained for 12 weeks vs placebo. PL9643 had a safety profile comparable to placebo. Results support the continued development of PL9643 as a novel therapeutic method for DED.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.