In the use of biological agents for treatment of eye disease, the back of the eye has been pretty much the sole domain thanks to the broad acceptance of anti-VEGF drugs for treatment of age-related macular degeneration, diabetic macular edema, and retinal vascular disorders, but the Italian biopharmaceutical firm Dompé has received US approval for the first biological agent for front-of-the-eye disease. The Food and Drug Administration approved its candidate Oxervate (cenegermin) for treatment of neurotrophic keratitis (NK). This also represents the first US approval of an agent utilizing recombinant human nerve growth factor (rhNGF).
The first-in-class rhNGF agent is delivered via drop to the corneal surface. The drug had received Orphan Drug Designation, Fast Track Status, Breakthrough Therapy Designation, and Priority Review from the FDA before its full marketing approval. This follows approval in Europe, where the product has been commercially available since October 2017. Chief medical officer Flavio Mantelli, MD, PhD, tells OIS Weekly that Dompé plans to launch the product in the US early next year.
Neurotrophic keratitis is a rare degenerative disease of the cornea caused by damage of the trigeminal nerve, which results in impairment of corneal sensitivity, spontaneous breakdown of the corneal epithelium, poor corneal healing and corneal ulceration, melting, and perforation. It can lead to vision loss. The trigeminal nerve, the largest of the cranial nerves, is responsible for sensory perception of the face, including the eyes. NK affects five out of every 10,000 people.
The initial clinical trial of Oxervate for NK evaluated both 10- and 20-micrograms per milliliter (µm/mL) concentrations. The safety profile was similar for both, Dr. Mantelli says, but the 20-µm/mL formulation appeared to exhibit greater trends in efficacy in some other measures, including reduction in lesion size, in the post-hoc analysis. Dompé made the decision to pursue the confirmatory clinical trial of the 20-µm/mL formulation. That showed approximately 72% of patients achieved complete corneal healing with a single eight-week cycle of treatment, and of those, 80% remained healed after one year, Dr. Mantelli reports. The 20-µm/mL formulation is the subject of the FDA approval.
Oxervate may represent a paradigm shift for the treatment of corneal degenerative disease, investigator Stephen C. Pflugfelder, MD, of Baylor College of Medicine, tells OIS Weekly. “Right now corneal specialists use a multi-pronged approach to these conditions,” he says. “Unfortunately, none of them have been confirmed by randomized clinical trials.” Existing treatments range from artificial tears in the early stages to autologous serum drops, amniotic membrane transplantation, or a tarsorrhaphy – a surgical procedure that involves sewing the eyelids together to provide temporary protection to the diseased corneal surface – for severe cases. “Corneal transplantation may need to be performed if neurotrophic corneal ulcers progress to perforation,” Dr. Pflugfelder says. “There is hope that early treatment with Oxervate may prevent progression to sight-threatening corneal perforation.”
Dr. Mantelli believes Oxervate has the potential to change the standard of care for neurotrophic keratitis the way anti-VEGF drugs did for retinal disease. “It can turn, at least from what we’ve seen in the clinical trials with one-year follow-up, a progressive disease into something that can be solved with an eight-week treatment cycle,” he says.
The science behind Oxervate stems from studies by Nobel laureate Rita Levi-Montalcini, who discovered the nerve growth factor with Stanley Cohen in the 1950s. The agent was developed with recombinant DNA technology that uses bacteria in which the DNA is introduced that allows the bacteria to produce the human growth factor on their own.
Dompé is ramping up production of Oxervate at its manufacturing facility in L’Aquila, Italy, (near Rome) to have a supply ready for its US launch in January 2019, Dr. Mantelli notes.
For questions about this article, contact Richard Mark Kirkner at Rich@healthegy.com.