RxPRODUCT NEWS PROFILE: Macugen (pegaptanib sodium)

More than 1.7 million individualsin the United States sufferfrom age-related maculardegeneration (AMD), an ocular conditionthat is the leading cause of blindnessin the elderly.1,2 By 2020, it is estimatedthat AMD could affect nearly 3million people.1 This progressive diseasecauses a reduction in a person'scentral vision, which is responsible forany activity that requires visual acuity,such as driving or reading.2 Thedecline in central vision is due to thedestruction of photoreceptors, orlight-sensitive cells, located in a portionof the retina called the macula.2

There are 2 types of AMD—dry(nonneovascular) and wet (neovascular).The common form is dry AMD,which is associated with a slow andprogressive loss of vision.2 In wet AMD,the more serious form, abnormal bloodvessels grow within the retina andeventually lead to serum and bloodleakage into the macula, causing rapidvision loss.2 Macugen (pegaptanib sodiuminjection), from Eyetech and Pfizer,was approved by the FDA in December2004 for the treatment of wet AMD.3

Pharmacology

Vascular endothelial growth factor(VEGF) is a protein responsible for activatingabnormal blood vessel growth inneovascular AMD.3 Macugen is a selectiveVEGF antagonist—the first in anew class of ophthalmic drugs knownas antiangiogenics.3 The inhibition ofVEGF will lead to a decrease in vascularpermeability and inflammation in thevascular endothelial cells and willreduce blood vessel growth, which willslow the progression of AMD.4

Clinical Trials

Macugen was studied in 2 multicenter,double-blind, randomized, controlledtrials in patients with neovascularAMD. Macugen or placebo injectionswere administered intravitreously into 1eye per patient every 6 weeks for a periodof 48 weeks.4 Approximately 1200patients over the age of 50 wereenrolled, with 298 patients receiving aplacebo injection and 892 patientsreceiving various doses of Macugen (294patients received 0.3 mg, 300 patientsreceived 1 mg, and 296 patients received3 mg). The primary end point was theproportion of patients losing fewer than15 letters of visual acuity from baselineuntil week 54 of assessment.5

Efficacy was demonstrated in all 3active-dose groups versus placebo inthe combined analysis of the primaryend point (P<.001 in the 0.3-and 1-mggroups; P = .03 in the 3-mg group). Inthe Macugen 0.3-mg group, 70% ofthe patients lost fewer than 15 lettersof visual acuity, versus 55% of thosereceiving placebo (P<.001). Also, 33%of the patients receiving 0.3 mg ofMacugen either maintained or gainedacuity, versus 23% of the controlpatients (P = .03). The risk of severevisual acuity loss, defined by losing 30letters of visual acuity or more, wasreduced by 12% in the group receiving0.3 mg of Macugen.5

Safety

The most common adverse eventsassociated with Macugen include anteriorchamber inflammation, blurredvision, cataracts, conjunctival hemorrhage,corneal edema, and general eyediscomfort.4 Proper aseptic technique isencouraged when administering Macugen,because intravitreous injectionshave been associated with endophthalmitis,an infection linked with thevitreous region, which potentially maybe vision-threatening.4,6 In addition,patients may experience an increase inintraocular pressure within 30 minutesof the injection.4 Patients should bemonitored closely for both conditionswhen they first receive therapy.

Outlook

Macugen appears to be an effectivetherapy for wet AMD, although long-termsafety is unknown.4 Macugencurrently is available in a single-use1-mL glass syringe containing 0.3 mg.The recommended dose is 0.3 mgintravitreously administered onceevery 6 weeks.4 Macugen is the first ina new class of ophthalmic drugs todirectly antagonize the protein VEGF,and it will provide both patients andhealth care practitioners with a newoption in the treatment of neovascularAMD.

Drs. Faria and Soo are both senior researchpharmacists with the Investigational DrugService at Brigham and Women's Hospital,Boston, Mass. Dr. Faria also is a seniorhuman research specialist at Partners Health-Care System. Mr. Patel is a sixth-yearPharmD Candidate from the MassachusettsCollege of Pharmacy, currently on a clinicalclerkship in the Investigational Drug Serviceat Brigham and Women's Hospital.

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