Neurotrophic Keratitis
What is Neurotrophic Keratitis?
Neurotrophic keratitis (NK) is a rare degenerative disease affecting the cornea. The cornea is the most densely innervated tissue of the body. Sensory innervation of the cornea is derived from the first branch of the trigeminal nerve. In addition to serving as an afferent arm of the blink and tear reflex, sensory corneal nerves also provide trophic support to the corneal epithelium while facilitating and maintaining ocular surface homeostasis. In patients with NK, the corneal sensory nerves are impaired leading to reduced corneal sensitivity and lack of trophic support to the corneal tissue. Without being able to sense external stimuli such as touch, wind, chemicals, light, heat and cold, the brain does not receive these critical signals to in turn respond with eyelid blinking and reflex tear production, which are protective for the corneal surface. Lack of these protective responses can cause the outer layer of the cornea, the epithelium, to thin and break down and cause an irregular surface distorting light and the tear film. As a result of the parallel lack of trophic support by corneal nerves, a detrimental loop is initiated, and the epithelial damage can progress to impairment of corneal healing, resulting in NK. In some cases, NK can progress and potentially lead to further damage such as ulceration and in severe cases perforation.
There was no FDA-approved treatment for neurotrophic keratitis until Dompé developed Oxervate®, the first recombinant human nerve growth factor.
*Not an Actual Patient
About Oxervate®
FDA granted cenegermin-bkbj ophthalmic solution “Breakthrough Therapy” designation as well as “Fast Track” and “Priority Review” status; expediting the review and approval of the drug, recognizing neurotrophic keratitis as a serious condition without FDA-approved drug treatments, and the potential for cenegermin-bkbj to fulfill this need, granting approval in 2018.
Our researchers were the first in the world to develop a revolutionary method to enable the production of cenegermin-bkbj. The difficulties of producing and storing the active ingredient and finding the appropriate pharmaceutical formulation for its therapeutic use have long been major obstacles in the development of the commercial manufacture of Oxervate®. Our research has enabled us to overcome these difficulties.
Neurotrophin Research
The field of neurotrophins research is growing and evolving to better understand its pleiotropic effects and mechanisms of action. At Dompé, we strive to lead the characterization of NGF protein variants, whether naturally acquired or biotechnologically engineered, to deepen our understanding of their effects on neuronal cell types.
Our goal is to identify and produce novel and more effective proteins suitable for drug development. By successfully charting the clinical development path of these molecular entities, we hope to offer our patients options for treatments of diseases for which none exist today.
Contact lenses should be removed before applying OXERVATE® because the presence of a contact lens (either therapeutic or corrective) could theoretically limit the distribution of cenegermin-bkbj onto the area of the corneal lesion. Lenses may be reinserted 15 minutes after administration.
OXERVATE® may cause mild to moderate eye discomfort such as eye pain during treatment. The patient should be advised to contact their doctor if a more serious eye reaction occurs.
In clinical trials, the most common adverse reaction was eye pain following instillation which was reported in approximately 16% of patients. Other adverse reactions occurring in 1% to 10% of OXERVATE® patients and more frequently than in the vehicle-treated patients included corneal deposits, foreign body sensation, ocular hyperemia, ocular inflammation and tearing.
USE IN SPECIFIC POPULATIONS
There are no data from the use of OXERVATE® in pregnant women to inform any drug associated risks.
The developmental and health benefits of breastfeeding should be considered, along with the mother’s clinical need for OXERVATE®, and any potential adverse effects on the breastfed infant from OXERVATE®.
The safety and effectiveness of OXERVATE® have been established in the pediatric population. Use of OXERVATE® in pediatric patients 2 years of age and older is supported by evidence from adequate and well-controlled trials of OXERVATE® in adults with additional safety data in children.
OXERVATE® (cenegermin-bkbj) ophthalmic solution 0.002% (20 mcg/mL) is indicated for the treatment of neurotrophic keratitis.
Instill one drop of OXERVATE® in the affected eye(s), 6 times a day at 2-hour intervals for eight weeks.
To report ADVERSE REACTIONS, contact Dompé U.S. Inc. at 1-833-366-7387 or FDA at
1-800-FDA-1088 or www.fda.gov/medwatch
Please see full Prescribing Information for OXERVATE®.
References
US-OXE-2300039 04/23