OXERVATE Eye drops, solution Ref.[7635] Active ingredients: Cenegermin

Pharmacotherapeutic Group: Ophthalmologicals, other ophthalmologicals
ATC code: S01XA24

Mechanism of action

OXERVATE contains cenegermin, a recombinant form of human nerve growth factor.

Nerve growth factor is an endogenous protein involved in the differentiation and maintenance of neurons, which acts through specific high-affinity (i.e., TrkA) and low-affinity (i.e. p75NTR) nerve growth factor receptors. Nerve growth factor receptors are expressed in the anterior segment of the eye (cornea, conjunctiva, iris, ciliary body, and lens), by the lacrimal gland, and by posterior segment intraocular tissues. The treatment with cenegermin, administered as eye drops, is intended to allow restoration of corneal integrity.

Pharmacodynamic effects

Various in vitro and in vivo animal data have shown that cenegermin binds the target receptors and promotes signal transduction and proliferation of neuronal and corneal epithelial cells.

In vitro and ex vivo experiments with human biomaterials have also illustrated the biological activity of cenegermin in terms of receptor affinity and potency, neuronal growth and differentiation.

Clinical efficacy and safety

The efficacy and safety of OXERVATE were evaluated in two multicentre, randomised, doublemasked, vehicle-controlled clinical studies (NGF0212 and NGF0214) in patients with moderate (persisted epithelial defect) or severe (corneal ulcer) neurotropic keratitis refractory to non-surgical treatments. In both studies patients received OXERVATE or vehicle 6 times daily in the affected eye(s) for 8 weeks, and underwent a follow-up period.

Study NGF0214 enrolled 48 patients (mean age 65±14 years, range 33-94 years) treated with OXERVATE 20 mcg/ml or vehicle (24 patients per arm). Study NGF0212 enrolled a total of 174 patients (mean age 61±16 years, range 18-95 years), who have been exposed to OXERVATE and vehicle without the L-methionine excipient; 156 patients were assessed independently for efficacy, comparing two different dosages of the medicinal product with 20 and 10 mcg/ml cenegermin to vehicle (52 patients per arm).

The table below summarizes the results for complete corneal healing of the persistent epithelial defect or corneal ulcer (the primary endpoint, defined as the greatest diameter of corneal fluorescein staining <0.5 mm) after 4 and 8 weeks of treatment for patients who received OXERVATE 20 mcg/ml or vehicle in the two studies.

The percentage of patients experiencing complete corneal clearing (grade 0 on the modified Oxford scale), the least squares mean change in best corrected distance visual acuity score (Early Treatment Diabetic Retinopathy Study letters) from baseline and any improvement in corneal sensitivity as measured in millimetres by Cochet-Bonnet aesthesiometry (difference compared to baseline >0) was also measured after 8 weeks of treatment in both studies, and summarized in the table below.

Patients considered completely healed at the end of 8 weeks of treatment with OXERVATE did not tend to have recurrences within the 12 months follow-up period of study NGF0212. Specifically, more than 80% of the 31 patients who were healed after initial OXERVATE 20 µg/ml treatment and for whom a response was available, remained completely healed at the end of the 12 months follow up period.

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with the medicinal product in one or more subsets of the paediatric population in neurotrophic keratitis (see section 4.2 for information on paediatric use).