Cenegermin API Manufacturers

General Description:

Cenegermin, identified by CAS number 1772578-74-1, is a notable compound with significant therapeutic applications. 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 . Neurotrophic keratitis is a degenerative disease resulting from a loss of corneal sensation . 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 . The prevalence of neurotrophic keratitis has been estimated to be less than five in 10,000 individuals . 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 . 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 . 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 . Cenegermin also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases .

Indications:

This drug is primarily indicated for: Cenegermin is indicated for the treatment of moderate (persistent epithelial defect) or severe (corneal ulcer) neurotrophic keratitis in adults . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Cenegermin undergoes metabolic processing primarily in: Ocularly administered cenegermin is mainly eliminated by tear secretion and the remainder mostly biotransformed by local tissue proteases . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Cenegermin are crucial for its therapeutic efficacy: 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 . Pharmacokinetic profiling of patients included in studies found no accumulation effect of cenegermin . In general, the systemic absorption of cenegermin is negligible . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Cenegermin is an important consideration for its dosing schedule: Half life data specific to human administration is not readily accessible or available . This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Cenegermin exhibits a strong affinity for binding with plasma proteins: In general, the systemic absorption of cenegermin is negligible . This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Cenegermin from the body primarily occurs through: Cenegermin administered by eye drops is mostly eliminated with the tear secretion . Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Cenegermin is distributed throughout the body with a volume of distribution of: 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 . At the ocular doses, cenegermin is not distributed throughout body tissues as there is no systemic absorption above the natural baseline levels . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Cenegermin is a critical factor in determining its safe and effective dosage: ALthough the systemic absorption of cenegermin is negligible in general , clearance data specific to human administration is not readily accessible or available . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Cenegermin exerts its therapeutic effects through: Little to no pharmacodynamic studies have yet been conducted in humans . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Cenegermin functions by: Cenegermin is a recombinant form of human nerve growth factor . Neurotrophic keratitis is a degenerative disease resulting from a loss of corneal sensation . 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 . 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 . 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 . The treatment with cenegermin, administered as eye drops, is intended to allow restoration of corneal integrity . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Cenegermin belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Cenegermin is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Biological Factors, Intercellular Signaling Peptides and Proteins, Nerve Growth Factors, Nerve Tissue Proteins, Ophthalmologicals, Peptides, Proteins, Recombinant Human Nerve Growth Factor, Sensory Organs. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.