New drug uses a recombinant human nerve growth factor.

Neurotrophic keratitis (NK) is a rare degenerative disease of the cornea due to impairment of the trigeminal nerve, resulting in loss of corneal sensitivity, corneal ulceration, scarring, melting and perforation. According to Sacchetti and Lambiase, it’s an orphan disease, affecting only approximately five in 10,000 people — still, as they say, “It isn’t rare when it’s in your chair.” Kenneth Beckman, MD, director of corneal surgery at Comprehensive Eyecare of Central Ohio, has treated more than half a dozen patients with this debilitating disease with Dompé’s Oxervate.

ABOUT OXERVATE

Oxervate ophthalmic solution 0.002% is the first topical biologic medication approved by the FDA for use in ophthalmology and the first treatment of any kind specifically indicated for NK that can promote healing. Oxervate contains the protein cenegermin, a recombinant human nerve growth factor (rhNGF) that is structurally identical to the nerve growth factor (NGF) made by the human body.

According to Georgea Pasedis, PharmD, head of Medical Affairs North America at Dompé US, endogenous NGF is a protein involved in the differentiation and maintenance of neurons. It acts through specific high-affinity (ie, TrkA) and low-affinity (ie, p75NTR) NGF receptors in the eye’s anterior segment, supporting corneal innervation, tear secretion, and corneal epithelial cell proliferation and differentiation.

CLINICAL TRIALS

Two independent, double-masked, randomized, multicenter, controlled clinical trials of Oxervate demonstrated its efficacy. The European study (REPARO) enrolled 156 patients (52 received 20 mcg/mL and 52 received 10 mcg/mL), and the U.S. study (NGF0214) recruited 48 patients, 24 of whom received 20 mcg/mL. After an 8-week course of treatment, up to 72% of patients achieved complete corneal healing, defined as the absence of staining in the corneal lesion and no persistent staining in the rest of the cornea. At 1-year follow-up, the REPARO study showed 80% of patients remained completely healed.

When a drug is that effective, one wonders what becomes of those in the control group. “Vehicle-treated patients who failed to achieve corneal healing, had a recurrence of NKor deteriorated during the initial 8-week vehicle treatment period of either study could receive Oxervate in a second, uncontrolled treatment period,”

Dr. Pasedis says. “In the REPARO study, 13 patients originally randomized into the vehicle group received Oxervate 20 mcg/mL for eight weeks during the uncontrolled treatment period, and corneal healing was achieved in eight of these 13 patients (61.5%). In the U.S. trial, 11 patients originally in the vehicle group received 20 mcg/mL of Oxervate in the uncontrolled treatment period. After 8 weeks, complete corneal healing was achieved in all 11 patients (100%).”

CORNEAL SENSITIVITY

In both studies, corneal sensitivity, as measured by a Cochet-Bonnet esthesiometer, was evaluated as a secondary efficacy variable. Over the 8-week treatment period, patients in the Oxervate group exhibited a greater clinical improvement in corneal sensitivity from baseline, as compared to the control group, although the difference was not statistically significant. Dr. Beckman concurs with a noticeable clinical improvement in corneal sensitivity, although he does not use an esthesiometer.

Natalie Afshari, MD, the chief of cornea and refractive surgery at the Shiley Eye Institute, University of California and a clinical investigator for Oxervate, concurs with the finding of a noticeable improvement in corneal sensitivity: “Because Oxervate is structurally identical to endogenous NGF, these neurotrophic corneas will have continued improvement in innervation over time.”

IN PRACTICE

Oxervate is instilled in the affected eye every 2 hours, six times a day, for 8 weeks, with no need to dose overnight. Patients receive a supply consisting of one carton per week. Each carton contains seven multidose vials in an insulated cooler and one delivery system kit, which contains seven vial adaptors (plus one extra), 42 pipettes (plus three extra), 42 sterile disinfectant wipes (plus three extra) and a dose card.

According to Dr. Beckman, patients are easily able to draw up the medicine into the syringe for a single use. He has used the drug on some severe cases of NK, and although it has taken a bit longer to work in these cases, patients saw good results. Further, “The 8-week course can be repeated, if necessary, and I have done so on one patient,” Dr. Beckman says.

Dr. Pasedis suggests that “a second round of treatment should initiate clinical investigation for the reason behind persistence of the lesion. Confirming adherence to the treatment regimen is vital to ensuring complete healing.”

Dr. Beckman also reports that Oxervate is well tolerated. Dompé reports the most common adverse effect as eye pain; other side effects include hyperemia, eye inflammation and more lacrimation.

OTHER POTENTIAL OPHTHALMIC INDICATIONS

According to Dr. Pasedis, Dompé recently announced the initiation of a Phase 2b clinical trial evaluating rhNGF for the treatment of dry eye disease.

Regarding other ophthalmic uses for rhNGF, “Dompé will continue exploration of rhNGF in formulations more suitable for delivery to the back of the eye, including application of rhNGF for neuroprotection in glaucoma,” Dr. Pasedis says.

FINANCIAL ACCESSIBILITY

Dompé launched the Connect to Care (C2C) program as a resource for patients. It includes information about Oxervate as well as details on obtaining insurance coverage and eligibility for financial assistance for out-of-pocket expenses.

“Thus far, with the C2C program, none of my patients have paid more than $100 for the entire course, and I believe most have not had to pay anything,” Dr. Beckman says. OM