Real Life Data on Efficacy and Safety of Topical NGF Eye Drops (Cenegermin)

Abstract

Background Topical NGF eye drops (Cenegermin) were approved in 2015 as an orphan drug for the treatment of neurotrophic keratopathy (NK). The active substance Cenegermin is a recombinant form of human NGF (nerve growth factor). Objectives Presentation of efficacy and safety of Cenegermin for use in patients in an university real-life setting. Material and Methods Retrospective study at the Köln University Eye Hospital from 2017 to 2019 with n = 11 eyes. Average follow-up was 13.5 ± 7.1 months. Reasons for treatment were neurotrophic keratopathy stage II and III, clinically mostly in combination with corneal neovascularization. Results Seven eyes with a NK II and 4 eyes with a NK III with a median observation period of 13.6 months (range 1.2 – 20.3 months) from a total of 11 patients were included. The median patient age was 42.8 ± 23.6 years (range 18 – 75 years). Before the start of therapy, the median erosion area measured 3.1 ± 1.4 × 1.9 ± 1.1 mm and the median ulcer area had a size of 2.3 ± 1.1 × 2.1 ± 0.8 mm. After the start of therapy with Cenegermin (application 6×/day), the epithelial defect closed in all 11 study eyes (100%) within 4 – 12 weeks (mean: 49 d ± 9 d). In 9 out of 10 patients (90%) pre-existing corneal neovascularization regressed significantly (p < 0.001). Before the start of therapy, a value in the Luneau test of 2.9 ± 1.9 (minimum 1/6, maximum 4/6) was found and rose to a median value of 4.2 ± 1.7 (minimum 2/6, maximum 6/6) after 18 months (p = 0.015). Therapy with Cenegermin had no long-term effect on intraocular pressure: the pressure ranged between 13.2 ± 4.1 mmHg (minimum 8 mmHg, maximum 21 mmHg). Under therapy with NGF eye drops, 67% of the patients, after an initial decrease, showed a long-term improvement in visual acuity (BSCVA) from 0.72 ± 0.31 to 0.46 ± 0.29 logMAR after 18 months (p = 0.005). Relapses in form of a corneal erosion in the long-term follow-up were observed in only one eye. One patient had to stop therapy because of local pain, no other local and systemic side effects were observed. Conclusion This real-life series on the use of Cenegermin in a university context shows a good effectiveness of the substance for epithelial closure in various underlying diseases (100% within 12 weeks). There is a long-term improvement in vision and corneal sensitivity. Larger real-life cohorts with various underlying diseases should follow.

Long-term clinical outcome and satisfaction survey in patients with neurotrophic keratopathy after treatment with cenegermin eye drops or amniotic membrane transplantation

“…Additional follow-up data from these studies showed that 87-96% of patients that received 8 weeks of cenegermin treatment remained recurrence free for up to 12 months [6]. Other studies have reported similar results in terms of epithelial healing and long-term recurrence rate [7,[24][25][26].…”

Neurotrophic Keratopathy Treated with Topical Recombinant Human Nerve Growth Factor (Cenegermin): Case Series Study with Long-Term Follow-Up

“…In the 3 cases of corneal ulcers due to NK treated with cenegermin, reported by Di Zazzo et al [ 22 ], the cause of NK was herpetic keratitis in 2 patients and immune keratitis in one, and all patients healed within 8 weeks therapy with cenegermin. Zwingelberg et al [ 19 ] reported the use of cenegermin in 11 patients with NK stages II and III, with epithelial healing and improvement in vision and corneal sensitivity after 18 months. Bruscolini et al [ 23 ] evaluated 18 patients with NK treated with cenegermin and reported recurrences in 4 patients: within the first 12 months in three and within the first 36 months in one.…”

“…Cenegermin is a recombinant human nerve growth factor produced by Escherichia coli that has shown efficacy and safety in promoting healing of corneal ulcers in patients with NK associated with persistent epithelial defects and improvements in other relevant endpoints, such as VA, corneal sensitivity, and disease progression [7]. The efficacy of cenegermin in NK demonstrated in clinical trials [8][9][10] has been confirmed by real-world descriptions of individual cases especially related to the pediatric use of the drug in children with rare congenital diseases [11][12][13][14] as well as in adult patients [15][16][17][18][19][20][21][22][23]. Here, we report the long-term results of 5 adult patients with NK treated successfully with cenegermin and followed for over a period of 4 years after healing of corneal ulcers.…”

Human recombinant nerve growth factor (Cenegermin) in a patient affected by primary congenital glaucoma with neurotrophic keratopathy

“…Safety and efficacy of Cenegermin have been evaluated in two double-masked studies, involving 151 patients with NK, restoring corneal integrity in 70% of subjects affected by moderate/ severe NK. 9,10 In 11 eyes affected with NK stage II or III, Zwingelberg et al 11 reported complete epithelial closure within 12 weeks of Cenegermin treatment, with long-term improvements in vision and corneal sensitivity.…”