August 2020

CORNEA

Pharmaceutical Focus
A look at Oxervate and treatment for neurotrophic keratitis


by Ellen Stodola Editorial Co-Director


Slit lamp photo of persistent epithelial defect (PED) in a patient with a history of zoster ophthalmicus; PED persisted despite placement of three amniotic membranes and autologous serum tears and eventually healed with Oxervate
Source: Anat Galor, MD

There are a number of treatment strategies for neurotrophic keratopathy that depend on the stage of the disease. Pedram Hamrah, MD, and Anat Galor, MD, discussed Oxervate (cenergermin, Dompe), which is currently the only FDA-approved medication for neurotrophic keratitis.
Dr. Galor said she uses autologous serum tears or amniotic membrane, explaining that Oxervate is not her first-line therapy because it is expensive.
Oxervate is a recombinant nerve growth factor. Its approval may be helpful to diagnose and start treating patients at earlier stages before the ulceration of the cornea happens and for patients with neurotrophic ulcers. Early stage neurotrophic keratopathy may be classified with punctate erosions and delayed epithelial healing.
Dr. Hamrah, who was involved in the initial randomized clinical trial for Oxervate, has prescribed it to a number of patients since its approval.
There were two randomized clinical trials, one in Europe and one in the U.S.
The European study was a large multicenter trial with 156 patients randomized into three groups: a placebo group and two different recombinant growth factors and concentrations (10 micrograms and 20 micrograms).1 The patients took six drops a day for 8 weeks. The data showed that while 20% of the placebo group did heal, the 10 and 20 microgram groups healed more than 50% at 4 weeks; at 8 weeks, 43% of the placebo group had healed compared to more than 70% of patients in the treatment groups.
The U.S. study included 13 sites and had two groups: one placebo and one with the 20-microgram recombinant nerve growth factor (the dosage shown to be more effective in the European study).2 Data showed that around 29% in the placebo group healed, and 70% in the treatment group healed, Dr. Hamrah said.
Since Oxervate’s FDA approval, Dr. Hamrah estimated that he has prescribed it to close to 20 patients.
In terms of insurance coverage, Dr. Hamrah said that the company has a multi-step process to assist with payment. The cost to the insurance is about $11,000 per week for up to an 8-week treatment.
When Oxervate is recommended, the physician and patient fill out an approval form, Dr. Hamrah explained, which is then sent to the insurance company. It generally takes 1–2 weeks for insurance to approve it. Once the insurance company approves it, it’s forwarded to the pharmacy and the pharmacy works with the patient to get the drug shipped to them on a weekly basis.
Dr. Hamrah said patients on Medicare and Medicaid have a copay. However, several patient assistance programs are available to patients that can partially help with this copay. So far, Dr. Hamrah said his patients have paid approximately $20–25 per week for the treatment.
Dr. Galor noted that the process of getting Oxervate for patients is labor intensive because the 8-week course is not shipped together. Patients get 1 week at a time, and it has to be refrigerated for use six times a day. There may also be a slight lag time of a couple of weeks from when Oxervate is prescribed to when the patient actually gets it.
Pain and discomfort are side effects associated with Oxervate. Dr. Hamrah said that these side effects were noted in the clinical trials. Around 10% of patients reported having discomfort while using it, but this resolved after discontinuation. The discomfort is only while the patient is on the treatment, he explained.
Nerve growth factor is the main neurotrophic factor required for the maintenance or regeneration of cornea nerves, Dr. Hamrah said, so by providing it directly to the eyes, the nerves that have been damaged from various causes in neurotrophic keratitis can start to regenerate. With regeneration, the epithelial surface layer will start to heal and persistent epithelial defects can close. The mechanism of the drug is the replenishment of a neurotrophic factor.
In terms of future treatments, Dr. Galor went into more detail about corneal neurotization, where you harvest a nerve and attach it to a nerve that works. Only a few centers in the country are doing this, she said, and it’s a more involved procedure, generally done by oculoplastic surgeons.
Dr. Hamrah thinks more treatment options are needed, to make treatments accessible to all patients and for patients who may not improve with Oxervate. He added that despite good results, Oxervate has shown to be effective in 70% of patients, so to have another treatment option for those 30% of patients who are not healing would be helpful.
There are several companies working on various drugs, he said, such as the biologicals ST266 or NRO-1 (GDNF) or morselized amniotic membrane and umbilical cord eye drops that are being studied in clinical trials or are under development.
“It’s an exciting time because it’s the first time we have a treatment for an orphan disease with which ophthalmologists have been struggling,” he said.

About the doctors

Anat Galor, MD
Bascom Palmer Eye Institute
Miami, Florida

Pedram Hamrah, MD
Tufts Medical Center
Tufts University School
of Medicine
Boston, Massachusetts

References

1. Bonini S, et al. Phase II randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis. Ophthalmology. 2018;125:1332–1343.
2. Pflugfelder SC, et al. Topical recombinant human nerve growth factor (cenergermin) for neurotrophic keratopathy: A multicenter randomized vehicle-controlled pivotal trial. Ophthalmology. 2020;127:14–26.

Relevant disclosures

Galor
: Dompe
Hamrah: Dompe, TissueTech, Neuroptika

Contact

Galor: agalor@med.miami.edu
Hamrah: PHamrah@tuftsmedicalcenter.org

A look at Oxervate and treatment for neurotrophic keratitis A look at Oxervate and treatment for neurotrophic keratitis
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