Topical BRM421 Ophthalmic Solution improves signs and symptoms of moderate to severe dry eye patients in clinical trials

Abstract

Purpose : BRM421 is a synthetic peptide comprising 29 amino acids derived from Pigment Epithelium-Derived Factor (PEDF) with neurotrophic and anti-inflammation properties. We performed two clinical studies to confirm the early onset of efficacy in subjects with different dry eye severities.

Methods : The first-in-human (FIH) study and second-in-human (SIH) study were multi-center, double-masked, randomized, vehicle-controlled, Ora CAE® screened studies. The FIH study evaluated 157 subjects. It comprised 5 visits in approximately 5 weeks. Based on the FIH study results, the SIH study evaluated 220 subjects in 4 visits in approximately 3 weeks.

Results : The FIH study showed that BRM421 treatment significantly improved sign in corneal sum (Ora Calibra® scale) in moderate to severe patients (higher baseline fluorescence corneal stain and central corneal staining score) at Visit 4 on Day 14 (BRM421 n=18, Placebo n=13, p=0.02). Significant improvement was also observed in symptom (ODS dryness, Ora Calibra® scale) on Day 14 (BRM421 n=22, Placebo n=22, p=0.01). In addition, the BRM421 group had superior Tear Film Break-Up Time at Visit 5 on Day 29 (p=0.03). The data suggest that BRM421 has an early onset of action; hence, the SIH study was designed for 4 visits. In the SIH study, BRM421 showed trending efficacy in sign (BRM421 n=81, Placebo n=83, p=0.11). Significant improvement was observed in the secondary endpoint of symptom in VAS–Eye Dryness (BRM421 n=108, Placebo n=111, p=0.02) and VAS-Burning (p=0.003) at Visit 3 on Day 8. Significant improvement was also observed in the Ora Calibra® Ocular Discomfort & 4-Symptom Burning/Stinging (BRM421 n=108, Placebo n=110, p=0.02) and Dryness (p= 0.03) in patient diary records on Day 8.

Conclusions : Both clinical studies confirmed consistent early onset of BRM421 treatment effects of sign and symptoms. The post hoc analyses showed improved efficacy in favor of BRM421 in a more severe patient population. The findings warrant further study of BRM421 Ophthalmic Solution in subjects suffering from dry eye syndrome.

This is a 2021 ARVO Annual Meeting abstract.