Dompé Announces China Approval of Oxervate® (Cenegermin) for Neurotrophic Keratitis

MILAN and SHANGHAI, Aug. 20, 2020 /PRNewswire/ -- Italian pharmaceutical company Dompé Farmaceutici announced today that the China National Medical Products Administration has approved its cenegermin ophthalmic solution (Oxervate^®) for the treatment of moderate to severe neurotrophic keratitis (NK)—a rare, progressive ocular disease that can lead to corneal scarring and vision loss^[1]。

“Neurotrophic keratitis is characterized by a complex etiology and a tendency for recurrent episodes. Many patients present with corneal epithelial defects or corneal ulcers at the time of consultation, requiring surgical intervention or long-term tarsorrhaphy, which causes significant inconvenience to their work and daily life,” stated Professor Shi Weiyun, Director of the Cornea Group of the Ophthalmology Branch of the Chinese Medical Association and President of Shandong Eye Hospital. “Studies have shown that Oxervate”^®"By promoting corneal healing and facilitating the regeneration and repair of corneal nerves, it is expected to transform the treatment approach for neurotrophic keratitis, offering new therapeutic options for patients with this rare disease."

Neurotrophic KeratitisNeurotrophic keratitis is a rare disease caused by impaired corneal nerve function. Its etiologies include herpes or other infections, ocular surface injury, ocular or neurological surgery, and certain systemic diseases, such as diabetes, that compromise corneal sensation and trophism. If not promptly diagnosed and managed, the condition progressively worsens, leading to persistent epithelial defects, corneal ulceration, stromal melting, perforation, and vision loss. To date, treatment options for neurotrophic keratitis remain limited to symptomatic management, rather than addressing the underlying etiology and corneal nerve damage. Current symptomatic treatments include artificial tears, autologous serum eye drops, tarsorrhaphy (a surgical procedure that partially sutures the eyelids together), and botulinum toxin-induced ptosis (to promote eyelid closure). Other surgical interventions aimed at restoring corneal integrity, such as conjunctival flap surgery and corneal transplantation, are invasive and may compromise both the aesthetic appearance and functional outcomes of the eye.^[1]。

Cenegermin is a novel recombinant human nerve growth factor (rhNGF) that is structurally identical to the nerve growth factor (NGF) protein naturally produced in the human body and present in ocular tissues. Oxervate^®It is on this basis that the successful development was achieved. This endogenous protein robustly supports corneal integrity through multiple mechanisms.^[2], and acts directly on corneal cells to stimulate cell growth and survival. Furthermore, NGF is known to bind to receptors on the lacrimal glands to promote tear secretion, providing lubrication and natural protection for the eyes against pathogens and injury. This protein has been proven to support corneal innervation, a neural function that is lost in neurotrophic keratitis.

Scientists discovered the regenerative potential of NGF and were awarded the Nobel Prize for this discovery; however, its therapeutic potential has not been translated into clinical applications in ophthalmology. Finally, the R&D center of Dompé Farmaceutici in L’Aquila, Italy, produced recombinant human NGF (cenegermin) through a proprietary development process. A series of subsequent trials conducted by the company confirmed the safety and efficacy of cenegermin in treating neurotrophic keratitis. Oxervate^®Representing the Field of OphthalmologyPioneeringtopical medication products, which also enable human nerve growth factor to be used as a drug or therapeutic agentFirst TimeApplication.

"Ocuvis"^®“This is the first product we have approved for market launch in China,” said Mr. Sergio Dompé, Chairman of Dompé Farmaceutici. “We are delighted to provide such an important therapy to patients with neurotrophic keratitis in China, and we extend our sincere gratitude to the numerous patients and physicians who actively participated in the clinical trials and contributed to the progress we have achieved today. As a leading Italian biopharmaceutical company with R&D at its core, we remain committed to exploring more innovative and valuable therapeutic solutions and care models to address the needs of complex diseases that lack treatment options. In the future, we will proactively and continuously introduce more innovative therapies and R&D projects to China, benefiting a greater number of Chinese patients.”

Ocuvis^®Approved for adult patients with moderate to severe neurotrophic keratitis, the 8-week treatment course allows patients to easily self-administer the medication, offering a new therapeutic option as monotherapy that can avoid invasive surgery.

Cenegermin Eye Drops (Oxervate)^®) Safety and Efficacy Data

Ocuvis^®The efficacy and safety have been confirmed in two independent, double-blind, randomized, multicenter, controlled clinical trials.^[3,4]. The project boasts the largest cohort of patients with neurotrophic keratitis in randomized controlled trials. Both trials investigated Oxervate in patients with moderate or severe neurotrophic keratitis.^®The efficacy and safety of monotherapy (20 μg/mL) were evaluated and compared with treatment using preservative-free artificial tear excipients. The European study NGF0212 (the REPARO study, with “REPARO” meaning “repair” in Latin) randomized 52 patients into subgroups; after 8 weeks of treatment, approximately 72% of patients in the treatment group achieved complete healing. The US-based study NGF0214 randomized 24 patients into subgroups, with 65.2% of treated patients achieving complete healing. The REPARO study included a longer follow-up period, which revealed that approximately 82% of patients who had achieved healing after the 8-week treatment course maintained stable healing status at one year.

Ocuvis^®Tolerability in clinical trials was quite favorable. Ocular pain is associated with Oxervate^®The most common adverse reaction was eye pain, reported by approximately 16% of patients, which may be associated with the restoration of sensation lost due to the disease. Other adverse events reported by more than 5% of patients included eye swelling (inflammation), increased tear production (lacrimation), and eye redness (conjunctival hyperemia). Findings from the REPARO trial were published in the September 2018 issue of Ophthalmology, the journal of the American Academy of Ophthalmology. Findings from the U.S. trial were published in the January 2020 issue of Ophthalmology.

On Neurotrophic Keratitis

The cornea is the most densely innervated tissue in the human body, with approximately 7,000 nerve endings per square millimeter. These nerves provide unique and irreplaceable support to the cornea; as corneal tissue is typically avascular, this innervation is essential for maintaining corneal transparency. In fact, corneal nerves help maintain ocular surface health by producing soluble factors known as neuromediators and by promoting sensation-dependent blink and tear reflexes.^[5]。

Neurotrophic Keratitis, also known as neurotrophic keratopathy, is a rare ocular disease caused by damage to any level of the fifth cranial nerve (trigeminal nerve). Causes of impaired corneal sensation include herpetic or other infections, ocular or neurological surgeries, physical trauma to the ocular surface, and certain systemic diseases that disrupt sensation. Neurotrophic keratitis can progress to corneal scarring and vision loss. Diagnosis, prognosis, and treatment are based on the severity of the disease, which is broadly classified into three stages. Stage 1 (mild) is characterized by ocular surface irregularity and decreased visual acuity; Stage 2 (moderate) is characterized by persistent epithelial defects (PED) that fail to heal; Stage 3 (severe) is characterized by corneal ulcers involving the subepithelial (stromal) tissue, which may progress to corneal melting and perforation. Patients with advanced neurotrophic keratitis are typically managed by cornea specialists.

References

1. Sacchetti M, Lambiase A. Diagnosis and Management of Neurotrophic Keratitis. Clinical Ophthalmology. 2014;8:571-9.

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. Bonini 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.

4. Chao W, Benitez Del Castillo JM, Dana R, Geerling G, Mantelli F, Massaro-Giordano G, Rama P. Healing of Persistent Epithelial Defects or Corneal Ulcer by Recombinant Human Nerve Growth Factor Eye Drops in Patients with Stage 2 or 3 Neurotrophic Keratitis. Presented at the Congress of the European Society of Ophthalmology (SOE), Barcelona, Spain, June, 10–13, 2017.

5. 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.

About Cenegermin Eye Drops (Oxervate^®）

Oxervate^®It is a topical ophthalmic solution administered as eye drops six times daily for 8 weeks to treat neurotrophic keratitis. The active ingredient is cenegermin, a recombinant human nerve growth factor—a protein endogenously produced in the human body. Nerve growth factor (NGF) exerts its effects by binding to specific high-affinity and low-affinity NGF receptors in the anterior segment of the eye, thereby supporting corneal innervation and tissue integrity.