Abstract
Purpose :
Neurotrophic keratitis (NK) is a degenerative corneal disease caused by impaired corneal innervation. Progression may lead to ulceration and vision loss. Therapeutic intervention that targets corneal innervation may improve corneal epithelial health and consequently optical clarity and visual acuity. We assessed the impact of cenegermin, a recombinant human nerve growth factor, or vehicle on visual acuity in patients with NK.
Methods :
A pooled analysis was performed on data from two randomized, double-masked, vehicle-controlled trials (NGF0212 [REPARO], NGF0214) that assessed efficacy and safety of cenegermin 20 mcg/mL or vehicle in patients with stages 2 and 3 NK. Both studies included adults ≥18 years old with stage 2 (persistent epithelial defect) or stage 3 (corneal ulcer) NK refractory to 1 or more non-surgical treatments and best-corrected distance visual acuity (BCDVA) ≤75 ETDRS letters. Prespecified secondary endpoints included mean change in BCDVA (logMAR) and percentage of patients with a 15-letter gain in BCDVA from baseline to week 8. Adjusted mixed model repeated model for mean change in BCDVA and chi-square test for 15-letter gain were used for comparison, and the statistical significance level was set at P=0.05.
Results :
152 patients were included in the full analysis set (N=76 cenegermin 20 mcg/mL; N=76 vehicle). Mean age was 62.6 ± 15 years, and patients were primarily female (61.8%) and white (89.5%) with diagnosed stage 2 (57.9%) or stage 3 (42.1%) NK. Mean BCDVA (logMAR) improvement from baseline to week 8 was significantly greater in patients treated with cenegermin compared with vehicle (baseline: 0.77 ± 0.370 vs. 0.71 ± 0.385, respectively; change from baseline: -0.35 ± 0.276 vs. -0.15 ± 0.237, respectively; P=0.0028). A 15-letter gain in BCDVA has been shown to represent a clinically meaningful improvement in patient-perceived visual function. Percentage of patients who experienced a 15-letter gain in BCDVA after 8 weeks of treatment was significantly higher in the cenegermin group than vehicle group (60.0% vs. 25.0%, respectively, P=0.0040).
Conclusions :
Compared with vehicle, 8 weeks of cenegermin treatment provided a clinically meaningful improvement in visual acuity in patients with stages 2 and 3 NK. These findings support the potential benefit of cenegermin in improving visual acuity in patients with moderate to severe NK.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.