/publications/issue/2005/2005-05/2005-05-9527

RxPRODUCT NEWS PROFILE: Macugen (pegaptanib sodium)

Author: Claudio Faria, PharmD, RPh; Carolyn Soo, PharmD, RPh; and Rajesh Patel

More than 1.7 million individuals in the United States suffer from age-related macular degeneration (AMD), an ocular condition that is the leading cause of blindness in the elderly.1,2 By 2020, it is estimated that AMD could affect nearly 3 million people.1 This progressive disease causes a reduction in a person's central vision, which is responsible for any activity that requires visual acuity, such as driving or reading.2 The decline in central vision is due to the destruction of photoreceptors, or light-sensitive cells, located in a portion of 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 and progressive loss of vision.2 In wet AMD, the more serious form, abnormal blood vessels grow within the retina and eventually lead to serum and blood leakage into the macula, causing rapid vision loss.2 Macugen (pegaptanib sodium injection), from Eyetech and Pfizer, was approved by the FDA in December 2004 for the treatment of wet AMD.3

Pharmacology

Vascular endothelial growth factor (VEGF) is a protein responsible for activating abnormal blood vessel growth in neovascular AMD.3 Macugen is a selective VEGF antagonist—the first in a new class of ophthalmic drugs known as antiangiogenics.3 The inhibition of VEGF will lead to a decrease in vascular permeability and inflammation in the vascular endothelial cells and will reduce blood vessel growth, which will slow the progression of AMD.4

Clinical Trials

Macugen was studied in 2 multicenter, double-blind, randomized, controlled trials in patients with neovascular AMD. Macugen or placebo injections were administered intravitreously into 1 eye per patient every 6 weeks for a period of 48 weeks.4 Approximately 1200 patients over the age of 50 were enrolled, with 298 patients receiving a placebo injection and 892 patients receiving various doses of Macugen (294 patients received 0.3 mg, 300 patients received 1 mg, and 296 patients received 3 mg). The primary end point was the proportion of patients losing fewer than 15 letters of visual acuity from baseline until week 54 of assessment.5

Efficacy was demonstrated in all 3 active-dose groups versus placebo in the combined analysis of the primary end point (P<.001 in the 0.3-and 1-mg groups; P = .03 in the 3-mg group). In the Macugen 0.3-mg group, 70% of the patients lost fewer than 15 letters of visual acuity, versus 55% of those receiving placebo (P<.001). Also, 33% of the patients receiving 0.3 mg of Macugen either maintained or gained acuity, versus 23% of the control patients (P = .03). The risk of severe visual acuity loss, defined by losing 30 letters of visual acuity or more, was reduced by 12% in the group receiving 0.3 mg of Macugen.5

Safety

The most common adverse events associated with Macugen include anterior chamber inflammation, blurred vision, cataracts, conjunctival hemorrhage, corneal edema, and general eye discomfort.4 Proper aseptic technique is encouraged when administering Macugen, because intravitreous injections have been associated with endophthalmitis, an infection linked with the vitreous region, which potentially may be vision-threatening.4,6 In addition, patients may experience an increase in intraocular pressure within 30 minutes of the injection.4 Patients should be monitored closely for both conditions when they first receive therapy.

Outlook

Macugen appears to be an effective therapy for wet AMD, although long-term safety is unknown.4 Macugen currently is available in a single-use 1-mL glass syringe containing 0.3 mg. The recommended dose is 0.3 mg intravitreously administered once every 6 weeks.4 Macugen is the first in a new class of ophthalmic drugs to directly antagonize the protein VEGF, and it will provide both patients and health care practitioners with a new option in the treatment of neovascular AMD.

Drs. Faria and Soo are both senior research pharmacists with the Investigational Drug Service at Brigham and Women's Hospital, Boston, Mass. Dr. Faria also is a senior human research specialist at Partners Health- Care System. Mr. Patel is a sixth-year PharmD Candidate from the Massachusetts College of Pharmacy, currently on a clinical clerkship in the Investigational Drug Service at Brigham and Women's Hospital.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@ascendmedia.com.