pegcetacoplan intravitreal

Action and Spectrum

Actions and Spectrum: 

Action: 

pegcetacoplan functions as a targeted C3 inhibitor, exerting its effect on the complement system within the ocular microenvironment. By selectively binding to C3, drug effectively inhibits the formation of C3 convertase, thereby impeding downstream activation of the complement cascade. This unique mechanism of action leads to a reduction in the generation of the anaphylatoxins C3a and C5a, mitigating inflammation and preventing the formation of the membrane attack complex (MAC).  

Spectrum: 

pegcetacoplan’s broad therapeutic spectrum encompasses various ocular conditions characterized by complement dysregulation and chronic inflammation. It has demonstrated efficacy in the treatment of diseases such as age-related macular degeneration ,geographic atrophy and paraneoplastic autoimmune retinopathy among others. 

Drug Interaction

Adverse Reaction

Frequency defined  

>10% 

Neovascular AMD (12%) 

Ocular discomfort (13%) 

1-10% 

Optic ischemic neuropathy (1.7%) 

Retinal hemorrhage (4%) 

Increased IOP (2%) 

Posterior capsule opacification (4%) 

Conjunctival hemorrhage (8%) 

Intraocular inflammation (4%) 

Punctate keratitis (5%) 

Vitreous detachment (4%) 

Vitreous floaters (10%) 

<1% 

Retinal tears 

Retinal detachment 

Hyphema 

Endophthalmitis 

Black Box Warning

Black Box Warning:  

None

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: Drugs should not be administered intravitreally in individuals with a known hypersensitivity or allergic reaction to the drug or its components. 

Active Ocular Infections: The intravitreal administration of pegcetacoplan is contraindicated in patients with active ocular infections, including bacterial, viral, or fungal infections. Use in such cases may exacerbate the existing infection or lead to the development of additional complications.  

Ocular Inflammation: In the presence of active intraocular inflammation, drug should not be administered intravitreally. The drug may worsen the inflammatory response and potentially result in adverse events.  

Preexisting Eye Conditions: Certain preexisting eye conditions may pose contraindications to the intravitreal administration of pegcetacoplan. These include significant vitreous hemorrhage, retinal detachment, or severe intraocular fibrosis. In such cases, alternative treatment options should be considered to avoid potential complications. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

Intravitreal pegcetacoplan is a novel therapeutic agent that has garnered significant interest in the field of ophthalmology. 

Pharmacodynamics:  

pegcetacoplan, a cyclic peptide, acts as a targeted inhibitor of the complement component 3 (C3) protein. By binding to C3 and preventing its cleavage, drug disrupts the formation of C3a and C3b, critical mediators of the complement cascade. This inhibition ultimately inhibits the downstream complement activation pathways, including the formation of the membrane attack complex (MAC). By modulating the complement system, pegcetacoplan offers a unique approach to mitigate the pathological inflammation and tissue damage associated with complement-mediated retinal diseases.   

Pharmacokinetics: 

Absorption 

After intravitreal injection, pegcetacoplan is expected to exhibit limited systemic absorption due to its large molecular weight and hydrophilic nature. The drug is designed to remain predominantly in the vitreous humor, where it can exert its therapeutic effects directly on the retina and retinal pigment epithelium (RPE) cells.  

Distribution 

Distribution studies of pegcetacoplan following intravitreal administration have demonstrated that the drug achieves high concentrations within the vitreous humor, retina, and RPE cells. The hydrophilic nature of pegcetacoplan restricts its movement across ocular barriers, limiting its distribution to the ocular tissues. The localized distribution of pegcetacoplan within the eye enhances its therapeutic efficacy while minimizing the risk of systemic exposure. 

Metabolism 

pegcetacoplan is a synthetic peptide and is expected to undergo minimal metabolism within the eye. The drug’s stability in the vitreous humor ensures its prolonged presence at the site of action, allowing for sustained complement modulation.  

Excretion and Elimination 

As pegcetacoplan is primarily confined to the ocular tissues following intravitreal administration, the excretion of the drug is expected to be negligible. Clearance from the eye may occur through physiological processes such as aqueous humor turnover or lymphatic drainage. 

Adminstartion

Administration:  

The procedure for administering pegcetacoplan intravitreally requires aseptic technique to minimize the risk of infection. The injection is typically performed in an outpatient setting, such as an ophthalmologist’s office or an ambulatory surgical center, under sterile conditions. Prior to the injection, the eye is prepared and draped to maintain a sterile field. 

The administration of pegcetacoplan intravitreally involves several steps. Firstly, the eye is topically anesthetized using an appropriate local anesthetic to minimize discomfort during the procedure. Next, the surface of the eye, including the conjunctiva, is cleaned and disinfected using an antiseptic solution. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: pegcetacoplan intravitreal 

Why do we use pegcetacoplan intravitreal?  

• One of the primary applications of Drug is in the treatment of geographic atrophy  secondary to age-related macular degeneration.  
• Another notable utilization of pegcetacoplan is in the management of other complement-mediated retinal disorders, such as paraneoplastic autoimmune retinopathy (PAR), retinal vasculitis, and autoimmune retinopathy associated with systemic diseases.  
• Drug may hold promise in the treatment of certain inflammatory ocular diseases, including uveitis and posterior scleritis.