• cenegermin is the first-ever application of a human nerve growth factor as drug or treatment, and is the first-ever topical biologic medication approved in ophthalmology.

• The first treatment specifically indicated for neurotrophic keratitis (NK), cenegermin has a mechanism of action that targets the root pathology of the disease.

• cenegermin was authorized by the European Medicines Agency (EMA) in 2017 and represents Dompé’s first approved therapy in the United States, where it received Orphan Drug Designation, Fast Track Status, and Breakthrough Therapy Designation, which led to Priority Review.

Milan, Italy and San Bruno, California, August 22 2018 – Dompé today announced that the U.S. Food and Drug Administration (FDA) has approved cenegermin, a breakthrough therapy for neurotrophic keratitis (NK), a rare and progressive eye disease that can lead to corneal scarring and vision loss.

“Neurotrophic keratitis can be disabling, hard to treat, and many patients do not respond well to existing therapies,” – said Reza Dana, Professor of Ophthalmology at Harvard Medical School, Director of the Cornea Service, Senior Scientist at the Massachusetts Eye and Ear, and Dompé medical advisor.. “By directly promoting corneal healing, Oxervate has the potential to change the way neurotrophic keratitis is treated, and may eventually result in a new standard of care for patients with this rare condition.”

Neurotrophic keratitis is a rare orphan condition that affects fewer than 65,000 persons in the United States based on estimated disease prevalence.1 It results from impaired function of corneal nerves, which can be caused by herpetic or other infections, ocular surface injuries, ocular or neurologic surgeries, and some systemic conditions that can impair corneal sensation. If unchecked, the disease can progress in severity, leading to persistent epithelial defects, corneal ulcers, melting, perforation and vision loss. Until now, treatment options for neurotrophic keratitis were limited to symptomatic treatments, which do not target the underlying disease pathology. These include artificial tears, antibiotics, autologous serum-derived eye drops, tarsorrhaphy (a procedure in which the eyelids are partially sutured together) and botulinum-induced ptosis (closure of the eyelid). Other surgical interventions, designed to restore the integrity of the cornea, include conjunctival flap surgeries and corneal transplants, which are invasive and can compromise the appearance and function of the eye.1

The drug is based on cenegermin-bkbj, a novel recombinant human nerve growth factor (rhNGF) that is structurally identical to the nerve growth factor (NGF) protein that is made in the human body, including in the ocular tissues. The endogenous protein supports corneal integrity though several mechanisms.2 NGF acts directly on corneal epithelial cells to stimulate their growth and survival. In addition, NGF is known to bind receptors on lacrimal glands to promote tear production, which may provide the eye with lubrication and natural protection from pathogens and injury. The protein also has been shown experimentally to support corneal innervation, which is lost in neurotrophic keratitis.

The regenerative potential of NGF was discovered by Nobel-prize winning scientists3, but its therapeutic potential was not realized in ophthalmology until Dompé’s research and development center in L’Aquila, Italy, created cenegermin-bkbj, a recombinant version of human NGF, through a unique development process. The company’s subsequent trials demonstrated the safety and effectiveness of cenegermin-bkbj for the treatment of neurotrophic keratitis. Oxervate represents the first-ever topical biologic medication approved in ophthalmology, and is the first ever application of a human NGF as drug or treatment.

“cenegermin represents the first therapy from Dompé that will be available in the United States,” said Sergio Dompé, Chairman of Dompé. “We are dedicated to delivering this important treatment to people living with neurotrophic keratitis and are grateful to the patients and physicians who participated in clinical trials and enabled this advancement.”

1Bonini S, Lambiase A, Rama P, Sinigaglia F, Allegretti M, Chao W, Mantelli F, for the REPARO Study Group. Phase II Randomized, Double-Masked, Vehicle-Controlled Trial of Recombinant Human Nerve Growth Factor for Neurotrophic Keratitis. Ophthalmology. 2018; 125:1332-43.

2 Mastropasqua L, Massaro-Giordano G, Nubile M, Sacchetti M. Understanding the Pathogenesis of Neurotrophic Keratitis: The Role of Corneal Nerves. Journal of Cellular Physiology. 2017; 232(4):717-24.

3 Levi-Montalcini R. The nerve growth factor 35 years later. Science. 1987 Sep 4; 237(4819):1154-62.