Cenegermin 20micrograms/ml eye drops preservative free

Background: Neurotrophic keratitis (NK) is a rare, degenerative disease of the cornea that arises from impaired trigeminal nerve innervation. The condition leads to progressive corneal anesthesia, epithelial breakdown, ulceration, and potential perforation. Cenegermin, a recombinant form of human nerve growth factor, is the first pharmacotherapy approved for this indication and operates through a disease-modifying mechanism that promotes corneal nerve regeneration. Objectives: To evaluate the therapeutic efficacy and safety profile of topical cenegermin (20 mcg/mL) compared with vehicle in adults with moderate to severe NK (Mackie classification stage 2 or 3) by quantitatively synthesizing evidence from randomized controlled trials (RCTs). Design: Systematic review and meta-analysis of RCTs, conducted in accordance with the PRISMA 2020 statement and the Cochrane Handbook for Systematic Reviews of Interventions. Data sources and methods: PubMed, Web of Science, and Cochrane CENTRAL were searched from inception through February 2026. Two double-masked, vehicle-controlled RCTs (the REPARO trial and the NGF0214 trial) enrolling 148 adults were included. Data were pooled using random-effects models (DerSimonian–Laird) and reported as risk ratios (RRs) with 95% confidence intervals (CI). Risk differences (RDs) and the number needed to treat (NNT) were also computed. Certainty of evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Results: Cenegermin substantially increased the probability of complete corneal healing at 8 weeks, with a pooled RR of 1.84 (95% CI 1.34–2.52; z  = 3.8; p  = 0.0001) and minimal between-study heterogeneity (I-squared = 0%; tau-squared = 0.00). The model-based pooled RD was 0.42 (95% CI 0.24–0.60), yielding an NNT of 3 (95% CI 2–5). The crude pooled event rates were 72.6% in the cenegermin group versus 38.7% in the vehicle group. Regarding safety, the pooled RR for any adverse event was 1.07 (95% CI 0.64–1.78; p  = 0.80), showing no significant difference between groups. The overall certainty of evidence was rated as moderate for both outcomes under the GRADE framework. Conclusion: Cenegermin is an effective and well-tolerated, disease-modifying therapy for moderate to severe NK. It nearly doubles the likelihood of complete corneal healing and represents an important addition to the therapeutic options available for this debilitating condition. Larger, independently funded trials with longer follow-up are warranted to confirm these findings and to establish its position within the treatment algorithm. Trial registration: PROSPERO CRD420251103148.

Abstract licence: CC BY-NC 4.0

Abstract Background Dry eye disease (DED) includes neurosensory abnormalities as part of its multifactorial etiology. Nerve growth factor is important for maintaining corneal nerve integrity and wound healing. Cenegermin (recombinant human nerve growth factor) is a topical biologic that promotes corneal healing in patients with neurotrophic keratitis. The purpose of this study was to evaluate efficacy and safety of cenegermin in moderate-to-severe DED and identify an optimal dosing strategy. Methods This was a phase II, multicenter, randomized, double-masked, vehicle-controlled, dose-ranging clinical trial in patients with moderate-to-severe DED, including Sjögren’s DED (NCT03982368). Patients received 1 drop of cenegermin 3 times daily (t.i.d.; 20 mcg/mL), cenegermin 2 times daily (b.i.d.; 20 mcg/mL) and vehicle once daily, or vehicle t.i.d. for 4 weeks. Follow-up continued for 12 additional weeks. The primary endpoint was change in Schirmer I score from baseline to week 4. Other key endpoints included rate of responders (Schirmer I test > 10 mm/5 min) after treatment and change in Symptoms Assessment iN Dry Eye (SANDE) scores from baseline to end of follow-up. A 1-sided test (α = 0.025) was used to evaluate statistical significance. Results At week 4, mean changes in Schirmer I scores were not statistically significantly different in either cenegermin group versus vehicle (cenegermin vs vehicle [treatment difference; 95% CI]: t.i.d., 2.60 mm and b.i.d., 3.99 mm vs 1.68 mm [t.i.d.: 0.93; −1.47 to 3.32, P = 0.078; b.i.d.: 2.31; −0.08 to 4.70, P = 0.066]). More patients responded to treatment with cenegermin t.i.d. and b.i.d. versus vehicle (t.i.d.: 25.9% [21/81, P = 0.028]; b.i.d.: 29.3% [24/82, P = 0.007] vs 11.9% [10/84]), with statistical significance (set at P < 0.025) observed in the b.i.d. group. Only cenegermin t.i.d. yielded statistically significant (P < 0.025) reductions in SANDE scores versus vehicle, which were sustained up to the end of follow-up (P value range, 0.002–0.008). Eye pain, primarily mild and transient, was the most frequently observed treatment-emergent adverse event with cenegermin. Similar results were observed in patients with Sjögren’s DED. Conclusions Cenegermin was well tolerated and although this study did not meet its primary endpoint, significant improvement in patient-reported symptoms of dry eye was observed through follow-up. Larger studies evaluating cenegermin in patients with DED are warranted. Trial registration NCT03982368; registered May 23, 2019.

Abstract licence: CC BY 4.0

ABSTRACT Introduction This study aimed to investigate the impact of cenegermin (recombinant human nerve growth factor) on corneal epithelial healing, nerve regeneration, and tear secretion in patients with diabetic neurotrophic keratopathy(DNK). Methods This study was conducted as a single-arm and open-label trial. Fourteen patients diagnosed with bilateral DNK were treated with cenegermin eye drops (20 mcg/ml) six times daily for eight weeks and followed up to twenty weeks. Clinical evaluations—including corneal fluorescein staining score, in vivo confocal microscopy, corneal sensitivity, and Schirmer I test—were conducted to assess the corneal epithelial healing time, nerve fibre regeneration, and tear secretion. Results The corneal epithelium exhibited complete healing in week 2, with further enhancement in epithelial integrity observed in week 8 and sustained until week 20. Corneal nerve fibre density (CNFD), length (CNFL), and branch density (CNBD) exhibited a significant increase at week 8 in all patients. However, CNFD and CNFL showed a slight reduction in the peripheral zones of patients with moderate DNK by week 20. Nonetheless, corneal sensitivity demonstrated consistent improvement throughout the treatment period. Tear secretion experienced a significant increase at week 8 but returned to baseline levels by week 20. Furthermore, the best-corrected visual acuity (BCVA) improved after treatment and remained stable until the final visit. Conclusions The administration of cenegermin effectively facilitated and sustained the healing process of corneal epithelium in cases of mild-to-moderate DNK by promoting nerve regeneration and tear secretion. Prolonged treatment is crucial for stimulating both nerve regeneration and tear secretion. Trial Registration: Chinese Clinical Trial Registry identifier ChiCTR2200058806 Key Messages What is known? Diabetic neurotrophic keratopathy (DNK), a subtype of neurotrophic keratopathy (NK) secondary to diabetes mellitus, is characterized by peripheral epithelial defects and varying degrees of corneal hypoesthesia or anesthesia. This condition exhibits poor responsiveness to conventional therapeutic approaches, leading to persistent or progressive lesions. The efficacy of rhNGF eye drops (cenegermin) in treating stage 2 and 3 NK has been evaluated in two prospective multicenter randomized clinical trials involving a limited number of patients with moderate and severe DNK. However, these studies do not provide sufficient evidence regarding the effects of rhNGF on tear function, corneal sensitivity and nerve density in mild and moderate DNKs. What is new? The study addresses a significant clinical challenge by investigating an optimized treatment approach for diabetic neurotrophic keratopathy (DNK), focusing on the complex interplay between the corneal nerve, epithelium, and lacrimal gland. The administration of cenegermin effectively facilitated and sustained the healing process of the corneal epithelium in cases of mild-to-moderate DNK that were refractory to conventional medical treatments and amniotic membrane transplantation (AMT). Noteworthy findings included significant regeneration of corneal nerve fibers and enhanced tear function. Prolonged administration is imperative for promoting nerve regeneration and stimulating tear secretion.

Abstract licence: CC BY 4.0

The ocular surface is susceptible to a wide spectrum of inflammatory, degenerative, and neurotrophic diseases that can impair vision. The complex pathophysiology and limited therapeutic options associated with these conditions continue to pose significant clinical challenges. Nerve Growth Factor (NGF), a neurotrophin initially recognized for its role in neuronal survival and differentiation, has emerged as a key regulator of ocular surface homeostasis and repair. Beyond its neurotrophic functions, NGF is suggested to influence epithelial proliferation, immune responses, tear secretion, and angiogenesis. Experimental and clinical studies have implicated NGF in both the pathogenesis and potential treatment of various ocular surface diseases, including allergic conjunctivitis, neurotrophic keratopathy (NK), immune-mediated and herpetic keratitis, and dry eye disease (DED), as well as post-surgical corneal wound healing. Notably, recombinant human NGF (rhNGF, cenegermin) has been approved as the first topical biologic therapy for NK. Despite encouraging clinical outcomes, challenges such as high treatment costs, limited long-term data, and potential proangiogenic effects remain. This review consolidates current evidence on the role of NGF in ocular surface health and disease, highlighting its biological mechanisms, clinical applications, and future therapeutic potential.

Abstract licence: CC BY