Company: Pfizer Ltd.
Legal category: POM.
Brand name: Macugen.
Active ingredient: Pegaptanib sodium 1.65 mg.
Presentation: Solution in prefilled syringe.
Price: 1, £514.00.
Indications: Treatment of neovascular (wet) age-related macular degeneration.
Pharmacology: Extensive evidence suggests that vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of several diseases of the eye in which neovascularisation and increased permeability occur. Based on this rationale, VEGF has been targeted to treat diseases such as neovascular age-related macular degeneration (AMD), which is the leading cause of irreversible severe vision loss in the over 50s in the developed world.
Pegaptanib is a selective antagonist of VEGF165 (the isoform that is preferentially involved in pathological ocular neovascularisation) that has been developed as a potential treatment for neovascular AMD. Pegaptanib is an aptamer or pegylated modified oligonucleotide which adopts a three dimensional conformation allowing it to bind to extracellular VEGF165. By binding with high affinity and specificity, VEGF165 is prevented from binding to its receptors on the surface of vascular endothelial cells. In this way, angiogenesis, vascular hyperpermeability and inflammation, normally induced by VEGF165, are inhibited. Pegaptanib does not bind to any significant degree to VEGF121, which is critical to physiological proliferation of blood vessels, and in animal studies, it has been shown to be effective at suppressing pathological neovascularisation, while sparing normal vasculature.
In two pivotal randomised double blind trials involving over 1,000 patients with all neovascular AMD lesion subtypes, the primary end point was defined as the proportion of patients who had lost fewer than 15 letters of visual acuity at 54 weeks. Seventy per cent of the patients given pegaptanib met this end point compared with 55% of the sham-injected controls. In addition, more patients in the pegaptanib group maintained their visual acuity or gained acuity than in the control group (33% vs 23%).
In these studies the effectiveness of pegaptanib, in terms of mean loss of acuity from baseline, was apparent from as early as six weeks and increased over the study period of 54 weeks. It was concluded that pegaptanib provided statistically significant and clinically meaningful benefit to patients with all types of neovascular AMD.
In an extension to these studies, patients were randomised for a further 48 weeks in order to compare the two-year efficacy of pegaptanib against sham injection and to assess the impact of discontinuing therapy after one year. This extension revealed a sustained treatment benefit during year 2 and the benefit appeared to be greater than after one year's therapy. No further safety concerns were identified and overall, pegaptanib was found to be effective at reducing the risk of vision loss and progression to legal blindness. Moreover, pegaptanib promoted stability of vision indicating that treatment should be initiated as soon as possible.
Adult Dose: 0.3 mg administered once every six weeks (9 injections per year) by intravitreal injection into the affected eye.
Child Dose: Under 18 years, not recommended.
Contraindications: Active or suspected ocular or periocular infection. Lactation.
Special precautions: Perfusion of optic nerve head and elevation of intraocular pressure should be carefully monitored and managed. Administration should be carried out by experienced ophthalmologists only. Pregnancy.
Adverse reactions: Endophthalmitis, anterior chamber inflammation, eye pain, raised IOP, punctate keratitis, vitreous floaters and vitreous opacities, cataract, conjunctival, retinal and vitreous haemorrhage, corneal dystrophy, oedema, discharge, inflammation, mydriasis, ocular discomfort, hypertension, periorbital haematoma, photophobia, photopsia, blurred vision, reduced visual acuity, visual disturbance, vitreous detachment/disorder, retinal detachment, headache, rhinorrhea. Rarely, anaphylaxis/anaphylactoid reactions.
? Report any adverse reaction to CHM.
Further information: Pfizer Ltd, Walton Oaks, Dorking Road, Tadworth, Surrey KT20 7NS. Tel: (01304) 616161.
Company: Pfizer Ltd.