Researchers have evaluated the safety and efficacy of topical recombinant human nerve growth factor ( rhNGF; Cenegermin; Oxervate ) for treating moderate-to-severe neurotrophic keratitis ( NK ), a rare degenerative corneal disease resulting from impaired corneal innervation.
The phase II multicenter, randomized, double-masked, vehicle-controlled trial has recruited patients with stage 2 ( moderate ) or stage 3 ( severe ) neurotrophic keratitis in 1 eye.
The REPARO phase II study assessed safety and efficacy in 156 patients randomized 1:1:1 to rhNGF 10 microg/ml, 20 microg/ml, or vehicle.
Treatment was administered 6 drops per day for 8 weeks.
Patients then entered a 48- or 56-week follow-up period.
Safety was assessed in all patients who received study treatment, whereas efficacy was by intention to treat.
Corneal healing ( defined as less than 0.5-mm maximum diameter of fluorescein staining in the lesion area ) was assessed by masked central readers at week 4 ( primary efficacy end point ) and week 8 ( key secondary end point ) of controlled treatment.
Corneal healing was reassessed post hoc by masked central readers using a more conservative measure ( 0-mm staining in the lesion area and no other persistent staining ).
At week 4 ( primary end point ), 19.6% of vehicle-treated patients achieved corneal healing ( less than 0.5-mm lesion staining ) versus 54.9% receiving rhNGF 10 microg/ml ( +35.3%; 97.06% confidence interval [ CI ], 15.88-54.71; P less than 0.001 ) and 58.0% receiving rhNGF 20 microg/ml ( +38.4%; 97.06% CI, 18.96-57.83; P less than 0.001 ).
At week 8 ( key secondary end point ), 43.1% of vehicle-treated patients achieved less than 0.5-mm lesion staining versus 74.5% receiving rhNGF 10 microg/ml ( +31.4%; 97.06% CI, 11.25-51.49; P = 0.001 ) and 74.0% receiving rhNGF 20 microg/ml ( +30.9%; 97.06% CI, 10.60-51.13; P = 0.002 ).
Post hoc analysis of corneal healing by the more conservative measure ( 0-mm lesion staining and no other persistent staining ) maintained statistically significant differences between rhNGF and vehicle at weeks 4 and 8.
More than 96% of patients who healed after controlled rhNGF treatment remained recurrence free during follow-up.
Treatment with rhNGF was well tolerated; adverse effects were mostly local, mild, and transient.
In conclusion, topical rhNGF is safe and more effective than vehicle in promoting healing of moderate-to-severe neurotrophic keratitis. ( Xagena )
Bonini S et al, Ophthalmology 2018;125:1332-1343