Identification
- Summary
Cenegermin is a recombinant human nerve growth factor used to treat neurotrophic keratitis.
- Brand Names
- Oxervate
- Generic Name
- Cenegermin
- DrugBank Accession Number
- DB13926
- Background
Cenegermin is a human beta-nerve growth factor (beta-ngf)-(1-118)- peptide (non-covalent dimer) produced in escherichia coli. It received European Union Approval in July, 2017 for the treatment of moderate to severe neurotrophic keratitis. Cenegermin received approval from the US FDA a year later in August of 2018 1.
Neurotrophic keratitis is a degenerative disease resulting from a loss of corneal sensation 1. The loss of corneal sensation impairs corneal health causing progressive damage to the top layer of the cornea, including corneal thinning, ulceration, and perforation in severe cases 1. The prevalence of neurotrophic keratitis has been estimated to be less than five in 10,000 individuals 1.
While the prevalence of neurotrophic keratitis is low, the impact of this serious condition and its associated sequelae on an individual patient can be debilitating. Many currently available therapeutic options for treating the condition involve surgical interventions - surgeries that are typically only palliative 1. The approval of cenegermin consequently provides a novel topical treatment that has the potential capacity to offer total corneal healing for many patients who may use the agent 1.
In particular, cenegermin was granted Priority Review designation, under which the FDA’s goal is to take action on an application within six months of application filing where the agency determines that the drug, if approved, would provide a significant improvement in the safety or effectiveness of the treatment, diagnosis or prevention of a serious condition 1. Cenegermin also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases 1.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Other protein based therapies - Protein Chemical Formula
- Not Available
- Protein Average Weight
- Not Available
- Sequences
- Not Available
- Synonyms
- Cenegermin
- cenegermin-bkbj
- rhNGF
Pharmacology
- Indication
Cenegermin is indicated for the treatment of moderate (persistent epithelial defect) or severe (corneal ulcer) neurotrophic keratitis in adults Label,3.
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- Contraindications & Blackbox Warnings
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Little to no pharmacodynamic studies have yet been conducted in humans Label.
- Mechanism of action
Cenegermin is a recombinant form of human nerve growth factor Label,3,4.
Neurotrophic keratitis is a degenerative disease resulting from a loss of corneal sensation 1. The loss of corneal sensation impairs corneal health causing progressive damage to the top layer of the cornea, including corneal thinning, ulceration, and perforation in severe cases 1.
Nerve growth factor is subsequently an endogenous protein involved in the differentiation and maintenance of neurons, which acts through specific high-affinity (i.e., TrkA) and low-affinity (i.e. p75NTR) nerve growth factor receptors Label,3,4. Nerve growth factor receptors are expressed in the anterior segment of the eye (cornea, conjunctiva, iris, ciliary body, and lens), by the lacrimal gland, and by posterior segment intraocular tissues Label,3,4. The treatment with cenegermin, administered as eye drops, is intended to allow restoration of corneal integrity Label,3,4.
Target Actions Organism UHigh affinity nerve growth factor receptor stimulatorHumans - Absorption
Cenegermin is mostly removed from the eye with the tear production and through the naso-lacrimal duct; the minor portion that is absorbed occurs mostly in the conjunctiva and peri-orbital tissue and to a minor extent through the cornea following ocular administration 3. Pharmacokinetic profiling of patients included in studies found no accumulation effect of cenegermin 3. In general, the systemic absorption of cenegermin is negligible 3.
- Volume of distribution
After eye drop administration, cenegermin is distributed particularly in the anterior portion of the eye, although a study with radiolabelled cenegermin in rats has shown that it also reaches the retina and other posterior parts of the eye at doses significantly higher than those administered by eye drops in humans to treat neurotrophic keratitis 3. At the ocular doses, cenegermin is not distributed throughout body tissues as there is no systemic absorption above the natural baseline levels 3.
- Protein binding
In general, the systemic absorption of cenegermin is negligible 3.
- Metabolism
Ocularly administered cenegermin is mainly eliminated by tear secretion and the remainder mostly biotransformed by local tissue proteases 3.
- Route of elimination
Cenegermin administered by eye drops is mostly eliminated with the tear secretion 3.
- Half-life
Half life data specific to human administration is not readily accessible or available Label.
- Clearance
ALthough the systemic absorption of cenegermin is negligible in general 3, clearance data specific to human administration is not readily accessible or available Label.
- Adverse Effects
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There are no data from the use of cenegermin in pregnant women Label,3. Systemic exposure to cenegermin is negligible or does not occur 3. As a precautionary measure, it is preferable to avoid the use of OXERVATE during pregnancy 3.
It is not known whether cenegermin is excreted in human milk Label,3. A risk to the suckling child cannot be excluded 3. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from this therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman 3.
The safety and effectiveness of cenegermin have been established in the pediatric population Label. Use of cenegermin in this population is supported by evidence from adequate and well controlled trials of cenegermin in adults with additional safety data in pediatric patients from 2 years of age and older Label.
Of the total number of subjects in clinical studies of cenegermin, 43.5 % were 65 years old and over Label. No overall differences in safety or effectiveness were observed between elderly and younger adult patients Label.
There are no data on the effects of cenegermin on human fertility Label,3.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
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Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Oxervate Solution / drops 20 ug/1mL Ophthalmic Dompé farmaceutici S.p.A. 2018-11-26 Not applicable US 
Oxervate Solution / drops 20 mcg/ml Ophthalmic Dompé farmaceutici S.p.A. 2020-12-22 Not applicable EU 
Oxervate Kit; Solution / drops 20 ug/1mL Ophthalmic Dompé farmaceutici S.p.A. 2018-11-26 Not applicable US Oxervate Solution 0.002 % Ophthalmic Dompé farmaceutici S.p.A. 2022-02-18 Not applicable Canada 
Categories
- ATC Codes
- S01XA24 — Cenegermin
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- B6E7K36KT8
- CAS number
- 1772578-74-1
References
- General References
- External Links
- 2104332
- Wikipedia
- Cenegermin
- FDA label
- Download (575 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Neurotrophic Keratopathy 1 3 Active Not Recruiting Treatment Dry Eye Syndrome (DES) 1 3 Active Not Recruiting Treatment Dry Eyes 1 2 Completed Treatment Dry Eye Syndrome (DES) 2 2 Completed Treatment Dry Eyes 1 2 Completed Treatment Macular Edema, Cystoid / Retinitis Pigmentosa (RP) 1 2 Completed Treatment Neurotrophic Keratopathy 1 2 Completed Treatment Ocular Discomfort 1 1 Completed Basic Science Healthy Subjects (HS) 1 1 Completed Treatment Glaucoma 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Kit; solution / drops Ophthalmic 20 ug/1mL Solution Ophthalmic 0.002 % Solution / drops Ophthalmic 20 MCG/ML Solution / drops Ophthalmic 20 ug/1mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Stimulator
- General Function
- Transmembrane receptor protein tyrosine kinase activity
- Specific Function
- Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympatheti...
- Gene Name
- NTRK1
- Uniprot ID
- P04629
- Uniprot Name
- High affinity nerve growth factor receptor
- Molecular Weight
- 87496.465 Da
Drug created at December 01, 2017 18:18 / Updated at August 07, 2021 00:11