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15331 details
Primary information
ID15331
Therapeutic IDTh1588
Protein NameCenegermin
Sequence>Th1588_Cenegermin SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRDPNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVR
Molecular WeightNA
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeHalf life data specific to human administration is not readily accessible or available [FDA Label].
DescriptionCenegermin 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 [L4563]. Neurotrophic keratitis is a degenerative disease resulting from a loss of corneal sensation [L4563]. 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 [L4563]. The prevalence of neurotrophic keratitis has been estimated to be less than five in 10,000 individuals [L4563]. 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 [L4563]. 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 [L4563]. 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 [L4563]. Cenegermin also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases [L4563].
Indication/DiseaseCenegermin is indicated for the treatment of moderate (persistent epithelial defect) or severe (corneal ulcer) neurotrophic keratitis in adults [FDA Label, F1502].
PharmacodynamicsLittle to no pharmacodynamic studies have yet been conducted in humans [FDA Label].
Mechanism of ActionCenegermin is a recombinant form of human nerve growth factor [FDA Label, F1502, F1503]. Neurotrophic keratitis is a degenerative disease resulting from a loss of corneal sensation [L4563]. 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 [L4563]. 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 [FDA Label, F1502, F1503]. 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 [FDA Label, F1502, F1503]. The treatment with cenegermin, administered as eye drops, is intended to allow restoration of corneal integrity [FDA Label, F1502, F1503].
ToxicityThere are no data from the use of cenegermin in pregnant women [FDA Label, F1502]. Systemic exposure to cenegermin is negligible or does not occur [F1502]. As a precautionary measure, it is preferable to avoid the use of OXERVATE during pregnancy [F1502]. It is not known whether cenegermin is excreted in human milk [FDA Label, F1502]. A risk to the suckling child cannot be excluded [F1502]. 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 [F1502]. The safety and effectiveness of cenegermin have been established in the pediatric population [FDA 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 [FDA Label]. Of the total number of subjects in clinical studies of cenegermin, 43.5 % were 65 years old and over [FDA Label]. No overall differences in safety or effectiveness were observed between elderly and younger adult patients [FDA Label]. There are no data on the effects of cenegermin on human fertility [FDA Label, F1502].
MetabolismOcularly administered cenegermin is mainly eliminated by tear secretion and the remainder mostly biotransformed by local tissue proteases [F1502].
AbsorptionCenegermin 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 [F1502]. Pharmacokinetic profiling of patients included in studies found no accumulation effect of cenegermin [F1502]. In general, the systemic absorption of cenegermin is negligible [F1502].
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 [F1502]. At the ocular doses, cenegermin is not distributed throughout body tissues as there is no systemic absorption above the natural baseline levels [F1502].
ClearanceALthough the systemic absorption of cenegermin is negligible in general [F1502], clearance data specific to human administration is not readily accessible or available [FDA Label].
CategoriesRecombinant Human Nerve Growth Factor
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetHigh affinity nerve growth factor receptor
Brand NameOxervate
CompanyDompé farmaceutici S.p.A.
Brand DescriptionDompé farmaceutici S.p.A.
Prescribed ForOphthalmic
Chemical Name20 ug/1mL
FormulationNone.
Physical Appearance eye pain, eye redness, eye inflammation, and increased tearing
Route of AdministrationOXERVATE ophthalmic solution contains cenegermin-bkbj, a recombinant form of human nerve growth factor produced in Escherichia coli.
Recommended DosageOXERVATE™(cenegermin-bkbj) ophthalmic solution 0.002% is indicated for the treatment of neurotrophic keratitis.
ContraindicationNA
Side EffectsNA
Useful Link 1Link
Useful Link 2Link
RemarksNA