Oxervate (cenegermin) eyedrops are effective and safe at promoting healing and reducing cornea lesions in patients with neurotrophic keratitis (NK), a clinical trial shows.
The results were reported in the study “Topical Recombinant Human Nerve Growth Factor (Cenegermin) for Neurotrophic Keratopathy: A Multicenter Randomized Vehicle-Controlled Pivotal Tria,” published in the journal Ophthalmology.
In people with NK, the cornea — the transparent protective outer layer of the eye — loses the ability to properly sense touch, temperature or pain because its outer-most layer (epithelium) breaks down due to damage to the corneal nerves.
In advanced cases, the inner layer of the cornea (stroma) also can be damaged, resulting in corneal thinning, corneal ulcers, scarring and, in more severe cases, vision loss.
Until recently, available treatments were nonspecific (e.g., preservative-free artificial tears, serum drops, and therapeutic lenses), while surgical interventions were reserved for recurrent cases.
Oxervate eyedrops (0.002% cenegermin), developed by Dompe, were the first treatment specifically indicated for NK to be approved by the U.S. Food and Drug Administration (FDA), in 2018.
The medicine also received marketing approval from the European Commission for treating moderate-to-severe NK in 2017.
Cenegermin, the active ingredient in Oxervate eyedrops, is a recombinant human nerve growth factor (rhNGF), a lab-made copy of NGF, a protein naturally produced in the body that supports the survival and growth of nerve cells. In the cornea, NGF is important for wound healing, tear secretion and maintenance of the corneal nerves.
Oxervate’s approval was based on the results of a pivotal Phase 2 clinical trial in the U.S. called NGF0214 (NCT02227147), and the results of the Phase1/2 REPARO trial (NCT01756456), a larger study conducted in Europe.
Both trials proved that Oxervate eyedrops were effective and safe in promoting corneal healing in patients with NK. However, effects on other clinically relevant outcomes (e.g., corneal sensitivity, visual acuity, and disease progression) were unclear in REPARO.
Here, researchers sought to clarify the benefits of Oxervate on these and other clinical endpoints (goals), based on data from the NGF0214 study.
The study included 48 adult patients with NK who had persistent defects in corneal epithelium (classified as NK stage 2), or who had a corneal ulcer (stage 3). Most common conditions underlying NK were herpes eye infection (19 patients), ocular surgery (eight patients), and dry eye disease (six patients).
Participants were assigned randomly to apply six drops daily of either Oxervate 20 mg/ml, or placebo, for eight weeks.
The trial’s primary goal was the percentage of patients with corneal healing after eight weeks of treatment, which was checked through imaging (staining) methods.
Additional outcomes included corneal healing after four weeks, overall changes in lesion size, rates of disease progression, and changes in visual acuity and corneal sensitivity.
Results confirmed improvements in corneal healing with Oxervate, compared to placebo, either by conventional or conservative definitions of healing. Of note, a conventional approach defines healing as less than 0.5 mm of lesion staining while a more conservative approach defines it as 0 mm of lesion staining and no other persistent staining.
By conventional criteria, 69.6% (16 of 23) of the patients using Oxervate were healed successfully, compared to 29.2% (seven of 24) of those given a placebo. If using a more conservative definition of healing, 65.2% (15 of 23) of those treated with Oxervate and 16.7% (four of 24) of those on a placebo had their corneas healed after eight weeks.
Oxervate reduced lesion size and lesion progression rates — defined as an increase in lesion size of 1 mm, progression in lesion depth to corneal melting or perforation, or both.
In the Oxervate group, five events of disease progression were recorded in five patients (21.7%), whereas half of the patients receiving placebo had 19 episodes of disease progression.
Oxervate tended to improve tear production, but did not seem to have a significant effect in visual acuity or corneal sensitivity, as compared to placebo.
The conditions that underlie NK seemed to have no association with patients’ healing outcome, although some disorders (e.g., corneal dystrophy, diabetes, and ocular surface injuries) were too rare to take solid conclusions.
Cenegermin was well-tolerated with side effects being mostly local, mild, and transient. The most common adverse side effect was eye pain (8.5% of patients in the trial’s main part).
No changes in vital signs, ophthalmic parameters, and lab workups were attributed to Oxervate.
“In summary, cenegermin ophthalmic solution represents a safe, novel, and noninvasive pharmacologic treatment for neurotrophic keratopathy and can become part of the treatment algorithm for this often difficult to manage disease with a high need for targeted and effective pharmacotherapies,” the researchers wrote.
Future studies, they add, may decipher the precise mechanism by which Oxervate benefits NK lesions. as well as its potential to treat other neurodegenerative diseases.
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