Abstract
Purpose :
Two double-masked, placebo-controlled, randomized, 12-week studies were analyzed to quantify the effect of PL9643 vs vehicle in the intent-to-treat (ITT) population and in the subpopulation of hyper-responders to the CAE® challenge model.
Methods :
The lead-in population in study 301 (Lead-In-301), consisting of the first 120 patients randomized, was analyzed. The Ora CAE challenge model controls the environment for relative humidity, airflow, and visual tasking and was used to standardize the evaluation of signs and symptoms of dry eye disease (DED). Patients with inferior corneal fluorescein staining >1, eye discomfort ≥25 over a 2-week run-in period, and a history of DED ≥5 years were randomized in a 1:1 ratio (PL9643:vehicle). Signs were analyzed using the ITT population; symptoms were analyzed in the hyper-responder subpopulation (58% of ITT population). A patient is defined as a CAE hyper-responder if their ocular discomfort worsens to 4 using the Ora Calibra® Ocular Discomfort scale (0 = none to 4 = worst) within 30 vs ≥30 minutes in CAE for a non hyper-responder.
Results :
For conjunctival sum Lissamine green staining at 12 weeks, PL9643 was superior to vehicle (mean, –0.50; P=0.045) and for inferior corneal fluorescein staining, PL9643 trended toward superiority over vehicle (mean, –0.25; P=0.097). In the hyper-responder population at 12 weeks and using a visual analog scale (VAS), PL9643 was superior to vehicle for pain (mean, –18.1; P=0.028). Eye discomfort (VAS mean, –7.9) and eye dryness (VAS mean, –8.4) trended toward superiority over vehicle. Topical PL9643 was well tolerated and adverse events were unremarkable. Similar results were observed in the PL9643 phase 2 study (PL9643-201).
Conclusions :
PL9643 has a novel mechanism of action and seems to protect the ocular surface from the damaging effects of inflammation. Based on the encouraging results from both studies, and the successful utilization of the Ora CAE challenge hyper-responder subpopulation, additional PL9643 trials are ongoing in which the hyper-responder population will be used to analyze DED symptoms. PL9643 may fill a number of important unmet patient needs in front of the eye conditions, including DED, by providing a safe and tolerable treatment option.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.