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    First-in-Class Rx for Neurotrophic Keratitis

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    A recombinant form of human nerve growth factor (rhNGF) has be­come the first FDA-approved drug for the treatment of neurotrophic keratitis (NK), a degenerative disease of the corneal epithelium that results from loss of corneal sensation.1 The drug—cenegermin (Oxervate, Dompé)—rep­resents 2 additional firsts: It is the first application of an rhNGF as a drug and the first topical biologic medication approved in ophthalmology. It may become available in the United States early next year.

    Urgent need. With NK, trigeminal nerve damage originates in the eye or the brain because of factors ranging from herpes eye infection to brain surgery, said Harminder S. Dua, FRCS, FRCOphth, PhD, at the University of Nottingham in the United Kingdom. Independently or simultaneously, NK then impairs sensory and trophic functions, including blinking, secretion of tears, and the nutritional health of corneal cells.2 Although NK affects few­er than 5 in 10,000 people, its impact can be severe, ranging from corneal thinning, ulceration, and perforation to visual impairment or blindness.3

    Alleviating the damage. Cenegermin was evaluated in 2 studies involving a total of 151 patients. Treatment in­volved 8 weeks of cenegermin eyedrops, delivered 8 times a day. Across both studies, 70% of patients treated with the drug experienced complete corneal healing, versus 28% in the control groups. Adverse reactions included eye pain and inflammation, ocular hyper­emia, and tearing. After 1 year, about 80% of those who were successfully treated remained free of disease.3

    “The studies were quite promising, but it was difficult to believe this was really possible until I saw it myself,” said Prof. Dua, who has now successful­ly treated 3 patients with severe cases of NK. Previously, he said, “We had sup­portive treatments such as lubricating drops, eye patching, autologous serum drops, tarsorrhaphy, and amniotic membrane patches. But we had nothing to treat the underlying disease.”

    A neural revival. Because rhNGF is involved in the development, main­tenance, and survival of nerve cells, cenegermin has the ability to address the root cause of NK and restore cor­neal integrity. “It revitalizes the nerves’ ability to secrete neuropeptides that support the health and regeneration of the corneal epithelium and the kerato­cytes of the stroma,” said Prof. Dua.

    Prior to treatment, corneal sensation was as low as 5 mm in his patients with NK, with 60 mm representing normal sensation, he said. “After treatment with Oxervate eyedrops, we’ve seen corneal sensation return to 50 mm. In addition, we can observe nerve regeneration using in vivo confocal microscopy. Al­though the new nerves are more coiled and tortuous, their sprouting in the cornea is very exciting.”

    Challenges ahead. Cenegermin requires frequent instillation. But NK patients may take that in stride, as many of them have already been using multiple drops several times a day, said Prof. Dua. A bigger challenge may be the weekly visits to the phar­macy, where drops must be frozen and released a batch at a time and then kept in the patient’s refrigerator for no longer than 7 days.

    “Another challenge is the cost of 2 months of treatment,” said Prof. Dua. In the United Kingdom, where clini­cians have had access to the drug since 2017, that cost is about £11,000 to £12,000, he said. U.S. pricing has yet to be determined.

    —Annie Stuart


    1 Voelker R. JAMA. 2018;320(13):1309.

    2 Dua HS et al. Prog Retin Eye Res. 2018;66:107-131.

    3 Bonini S et al. Ophthalmology. 2018;125(9):1332-1343.


    Relevant financial disclosures—Prof. Dua: Dompé: C.

    For full disclosures and the disclosure key, see below.

    Full Financial Disclosures

    Dr. Chen U.S. Department of Defense: S; Harvard Foundation Grant (Fidelity Charitable Fund): S.

    Dr. Drenser Interview Medical Systems: O,P; Phoenix: O; Retinal Solutions: O,P; Spark Therapeutics: C.

    Prof. Dua Croma: C; Dompé: C; GlaxoSmithKline: O; NuVision Biotherapeutic: O; Santen: C; Shire: C; Thea: C; VisuFarma: C.

    Dr. Kelly U.S. Department of Defense: S; Neuro Kinetics: S.

    Disclosure Category



    Consultant/Advisor C Consultant fee, paid advisory boards, or fees for attending a meeting.
    Employee E Employed by a commercial company.
    Speakers bureau L Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
    Equity owner O Equity ownership/stock options in publicly or privately traded firms, excluding mutual funds.
    Patents/Royalty P Patents and/or royalties for intellectual property.
    Grant support S Grant support or other financial support to the investigator from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and/or pharmaceutical companies.


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