By: Paul M. Karpecki, OD, FAAO Clinical Director – PECAA
I have to credit the FDA as we’ve seen more approvals for ocular drugs and devices than at any time I can recall in the past. In the last 90 days we had a new drug approved for dry eye disease, a low dose corticosteroid for cataract surgery, a drug for neurotrophic keratitis and what might be the most effective MIGs procedure to date. The remaining new therapeutic is a nerve growth factor solution for neurotrophic keratitis that should be available in early 2019.
For a recap of other recent ocular approvals, please refer to part 1 and part 2 of ‘The FDA Goes Into Hyperdrive With Approvals.’
OXERVATE (cenegermin-bkbj) ophthalmic solution for Neurotrophic Keratitis
Oxervate 0.002% ophthalmic solution is recombinant human nerve growth factor indicated for the treatment of neurotrophic keratitis. Neurotrophic keratitis is often observed in patients who have had HSV keratitis or herpes zoster ophthalmicus. It can also occur in longstanding dry eye disease patients such as those with Sjogrens’ Syndrome. The dosing of Oervate is q2h or 6 times per day for 8 weeks. In the clinical trial leading to FDA approval the most common side effects (incidence >5%) were eye pain, redness, inflammation and increased tearing.
It has a unique storage requirement in that it is kept frozen at the pharmacy but once the patient receives insulated container, they remove a weekly carton they can store fridge for 14 days, keeping the others in the freezer. Instructions are provided for setting up the multi dose vial which is closed with a rubber stopper (no latex), and an aluminum over-seal. Instruct the patient to only remove the number of OXERVATE vials required for use over the course of a single day. They do not need to and should not shake the vials.
Once opened, the vial can be kept in the original weekly carton in the refrigerator or at room temperature up to 77°F (25°C), but must be used within 12 hours.
The drug is approved from age 2 and older for neurotrophic keratitis. Although it’s rare for children to experience this, some of the more common causes are chronic dry eye disease, HSV keratitis, Herpes Zoster or Shingles, patients with diabetes etc. Patients will often manifest a decreased sensitivity when testing with a cotton wisp or dental floss.
Mechanism of Action
Nerve growth factor is an endogenous protein involved in the differentiation and maintenance of neurons. These neurons act through high-affinity (i.e., TrkA) and low-affinity (i.e. p75NTR) nerve growth factor receptors in the anterior segment of the eye. This new drop would support corneal innervation and integrity. Healing the nerves is essential to healing the eye/cornea in numerous neurotrophic conditions including persistent epithelial defects, neuropathic dry eye, and persistent SPK.
In the pivotal clinical trial for FDA approval, the end point for success was complete corneal healing defined as the absence of corneal lesion staining and no persistent staining of the cornea after 8 weeks of treatment. The results were significant for OXERVATE compared to placebo as seen in table 1.
This is a very exciting approval and will serve a significant unmet need for many people suffering from neurotrophic corneal issues. Patients appreciate your knowledge and access to what might be best for them. Staying on top of the latest developments, will likely help grow your practice as well.