EMA committee recommends cenegermin for neurotrophic keratitis

A committee of the European Medicines Agency has recommended approval of cenegermin (Oxervate, Dompé) eye drops for neurotrophic keratitis.

There is no effective therapy available for this debilitating condition and it is extremely rare, affecting only five in 10,000 people.

Because of this, the agency designated cenegermin an orphan drug in 2015, and the Committee for Human Medicinal Products (CHMP) completed its review through an accelerated assessment, beginning in November 2016 and ending on 18th May this year.

"We welcome the CHMP opinion with great satisfaction,” said Dompé’s Chief Executive Officer Eugenio Aringhieri in a press release.

In neurotrophic keratitis, damage to the trigeminal nerve or its branches causes loss of sensation in the cornea.

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, which can lead to corneal ulcers, perforation, infection, and scarring.

Currently, there are no medical treatments that can induce corneal healing in patients with neurotrophic keratitis, though discontinuation of medications that have caused the syndrome may help. There is also no medication currently available that can restore decreased corneal sensitivity.

Naturally occurring protein

Cenegermin is the recombinant version of the human nerve growth factor (NGF) discovered by Nobel Laureate Dr 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 NGF.

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

The CHMP based its recommendation on the results of two phase II clinical trials involving 204 patients with moderate and severe neurotrophic keratitis.

In both studies, after eight weeks a higher number of patients treated with cenegermin experienced complete corneal healing than patients receiving a placebo.

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

“In the future, our goal is to keep investigating its potential in other pathologies, to allow more and more patients to benefit from this innovative therapeutic approach,” Aringhieri said in the press release.

Decision pending

Decision pending

If approved, Oxervate eye drops will be available at a dosage of 20 µg/ml. The drug has not yet been granted marketing authorisation in any country.

The CHMP's recommendation will go to the European Commission for a decision on to grant European Union-wide marketing authorisation, while the Committee for Orphan Medicinal Products will determine whether to maintain orphan designation.

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