Cenegermin receives European Commission marketing authorization

The European Commission has granted marketing authorisation for cenegermin eye drops (Oxervate, Dompé) for the treatment of moderate to severe neurotrophic keratitis.

It is the first drug authorised by the European Commission for adults in Europe with neurotrophic keratitis, a severely debilitating eye disease which affects fewer than 5 out of 10,000 people.

Related: EMA committee recommends cenegermin for neurotrophic keratitis

“Considering the severity of the disease and the lack of viable alternatives, having a therapeutic option that can act on corneal lesions is an important development for the community of ophthalmologists and to the patients themselves,” said Harminder Singh Dua, chair and professor of ophthalmology, University of Nottingham.

Cenegermin received orphan drug designation for neurotrophic keratitis in 2015.

In this condition, damage to the trigeminal nerve or its branches causes loss of sensation in the cornea. In the most severe cases, it can lead to ulcers, aseptic necrosis and corneal perforation, resulting in impaired vision of those affected.

The initial damage can result from herpes simplex and herpes zoster viral infections, trigeminal neuralgia surgery, acoustic neuroma, and toxicity from chronic use of topical ocular medications.

The sensory neurons in the cornea directly influence the integrity of the corneal epithelium; without them epithelial cells swell, lose microvilli, and produce abnormal basal lamina. This can slow mitosis, leading to epithelial breakdown.

This makes the cornea prone to injury that can lead to corneal ulcers, perforation, infection, and scarring.

Discontinuation of medications that caused the syndrome may allow healing, but until now, no medication could restore decreased corneal sensitivity or induce corneal healing.

Cenegermin is the recombinant version of the human nerve growth factor (NGF) discovered by Nobel Laureate Rita Levi Montalcini. This protein is naturally produced by the human body and is involved in the development, maintenance, and survival of nerve cells.

Dompé produces cenegermin through recombinant DNA technology, with the introduction of a gene (DNA) into bacteria, causing them to produce the human nerve growth factor.

Nerve regeneration

Administered in the form of eye drops to patients with neurotrophic keratitis, cenegermin could promote nerve regeneration, leading to repair the corneal damage.

Two phase II clinical trials involving 204 patients with moderate and severe neurotrophic keratitis showed that after eight weeks a higher number of patients treated with cenegermin reached a complete corneal healing than patients receiving a placebo.

The most common adverse reactions observed with cenegermin include eye pain, eye inflammation, increased lacrimation, eyelid pain, and foreign body sensation in the eye.

Oxervate will be available as a 20 µg/ml eye drops solution.

Dompé is also exploring the use of cenergermin in other optic neuropathies, such as retinitis pigmentosa, glaucoma, dry eye disease, and retinitis pigmentosa.

Meanwhile, researchers at Yamaguchi University and Hiroshima University are pursuing a similar approach to the treatment of neurotrophic keratitis using a combination of the neurotransmitter substance P and insulin-like growth factor 1 (IGF-1).

Researchers elsewhere are investigating extracellular matrix regenerators, sulfate analogs that protect and stabilize the action of such growth factors as FGF-1, FGF-2, TGFbeta-1, and VEGF.

These compounds stimulate the synthesis of collagen and glycosamineglycanes and inhibit the action of enzymes such as elastase, haparanase, or plasmin, all of which enhances the process of extracellular matrix remodeling and regeneration. A phase III multicenter trial of one formulation, Cacicol (Thea) is also underway.

Autologous serum and platelet-rich plasma are also being researched.

Oxervate is Dompé’s first biotechnical drug. “Neurotrophic keratitis is a rare disease that is particularly debilitating, and until now, patients have had no treatment options,” said Eugenio Aringhieri, the company’s chief executive officer. “The European Commission adopted decision is a milestone for patients affected by this disease, for the research in this sector, and for our Company.”

The company will now seek approval for the drug in markets outside Europe, he said.