PALM BEACH GARDENS, FL--(Marketwire - June 05, 2010) - Eyetech Inc. announced that positive results from a Phase 3 study of Macugen® (pegaptanib sodium) in patients with diabetic macular edema (DME) were presented today at the World Ophthalmology Congress in Berlin. In the primary efficacy endpoint of the study, 37% of patients treated with Macugen gained two lines, or 10 letters, of vision on the ETDRS eye chart at 54 weeks, compared to 20% of patients who received a sham procedure, a placebo-like simulated injection in the eye (p=0.0047). DME is a common complication of diabetes and a leading cause of blindness in people of working age. (1)
The Phase 3 study, conducted by Pfizer Inc., met its primary endpoint of the number of patients treated with Macugen who gained greater than ten letters of vision at one year compared to patients who received a sham procedure. Eyetech Inc. markets and sells Macugen in the United States, and Pfizer Inc. markets and sells Macugen outside of the United States.
On average, patients treated with Macugen in the study gained 5.2 letters of vision at year one compared to 1.2 letters for patients receiving a sham procedure (p < 0.05). At the end of year two, patients receiving Macugen had gained on average 6.1 letters of vision compared to 1.3 letters for patients in the sham arm of the study (p < 0.01). All patients enrolled in the study were eligible to receive laser therapy, the current standard of care for DME, beginning at week 18 of the study at the physician's discretion using ETDRS guidelines.
"In this large Phase 3 study, investigators observed significant and sustained vision improvement over two years in patients with DME treated with Macugen," said Steven Bettis, president and co-founder of Eyetech Inc. "These data suggest that Macugen may have the potential to be an alternative or addition to laser therapy, the current standard of care for patients with DME."
Results of the Phase 3 study are similar to previously published data from a Phase 2 Study of Macugen in patients with DME (2). In the Phase 2 study of 172 patients with DME, 34% of patients treated with 0.3 mg of Macugen gained two lines of vision at 36 weeks, compared with 10% of patients who received a sham procedure (p=0.003).
"The visual improvement reported in this Phase 3 study is encouraging news for physicians and patients who manage DME, a serious and increasingly common complication of diabetes," said Victor H. Gonzalez, M.D., of the Valley Retina Institute in McAllen, Texas. "A growing body of evidence suggests that anti-VEGF therapy may play an important role in the management of DME, a sight-threatening disease that affects people during the most productive years of their lives."
About the Study
Study A5751013 is a multicenter, randomized, sham-controlled, double-masked, comparative Phase 3 trial over two years with an open-label year-three extension. The primary analysis included 260 patients with DME at 56 global sites. The primary objective of the study was to evaluate whether Macugen improved vision compared with sham injections in patients with DME, and to assess the safety of Macugen in these patients.
In this fully masked study, patients received an injection of 0.3 mg Macugen or a sham procedure every six weeks for a total of nine injections in year one. In year two, subjects could receive injections as often as every six weeks based on pre-specified criteria, including visual acuity, clinical examination, optical coherence tomography (OCT) and the opinion of the investigator. Up to three focal or grid laser treatments per year were permitted beginning at week 18, also at the investigator's discretion using ETDRS guidelines, in both arms. There was also an option for patients to be enrolled in an open-label year-three extension.
The primary outcome measure of the study was the proportion of subjects who, after one year, experienced an improvement in vision from baseline of two lines, or 10 letters, on the ETDRS eye chart. The study also collected data on a number of secondary outcome measures at one and two years, including the proportion of subjects with an improvement in vision at two years, changes in average visual acuity over time, proportion of eyes experiencing a change in the degree of retinopathy, the use of laser photocoagulation therapy, optical coherence tomography (OCT), vision-related quality of life, and safety. Additional results will be submitted for presentation at a future medical meeting.
There were no new or unexpected safety signals in the study. The most common treatment-emergent adverse events occurred in the eye; this included conjunctival hemorrhage (22%), eye pain (10%), punctate keratitis (11%), and diabetic retinal edema (11%). An increase in intraocular pressure related to the injection procedure was another common treatment-emergent adverse event and was noted in 17 patients treated with Macugen and in 7 patients treated with sham. Cardiac disorders were the most common, serious, treatment-emergent adverse events; these were reported in 6.9% of patients treated with Macugen and 5.6% of patients treated with the sham procedure. No deaths were related to the injection procedure or study drug. Adverse events were consistent with those observed in clinical trials of Macugen in patients with neovascular age-related macular degeneration (wet AMD) and similar to clinical experience with Macugen.
About Diabetic Macular Edema (DME)
Diabetic macular edema (DME) is a common form of diabetic retinopathy, an eye disease caused by damage to the blood vessels of the retina in the back of the eye and the leading cause of blindness among working-age adult populations (20 to 65 years). (3) DME occurs when damaged blood vessels leak fluid into the center of the macula, the area of the retina responsible for sharp, straight-ahead vision. The fluid makes the macula swell and causes blurry vision. When left untreated, 25% of people with DME will develop moderate vision loss within three years.(4) There are no pharmaceutical therapies available today for patients with DME.(5) Currently available treatment options for DME consist of two main types of laser therapy: focal and grid photocoagulation. These therapies have limitations and are generally not used in patients with edema in the center of the macula.
The International Diabetes Federation estimates that 285 million people around the world have diabetes and approximately 14% of people with diabetes have DME. Prevalence of DME increases to 29% for people with diabetes who use insulin for more than 20 years.(5) By 2030, the incidence of diabetes is expected to rise to 438 million worldwide, and the incidence of diabetes-related eye complications, like DME and diabetic retinopathy, are also expected to continue to increase worldwide.
Macugen, a selective inhibitor of VEGF-165, is approved in the United States for the treatment of neovascular age-related macular degeneration (neovascular AMD) and is administered in a 0.3-mg dose once every six weeks by intravitreal injection. Macugen is a pegylated anti-VEGF aptamer, which binds to vascular endothelial growth factor (VEGF). VEGF is a protein that plays a critical role in angiogenesis (the formation of new blood vessels) and increased permeability (leakage from blood vessels), two pathological processes that contribute to the vision loss associated with neovascular AMD. For full prescribing information about Macugen, please visit www.macugen.com.
Important Safety Information
Macugen is contraindicated in patients with ocular or periocular infections or with known hypersensitivity to pegaptanib sodium or any other excipient of this product.
Safety or efficacy of Macugen beyond two years has not been demonstrated.
Intravitreal injections including those with Macugen have been associated with endophthalmitis. Proper aseptic injection technique -- which includes use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent) -- should always be utilized when administering Macugen. In addition, patients should be monitored during the week following the injection to permit early treatment, should an infection occur.
Increases in intraocular pressure (IOP) have been seen within 30 minutes of injection with Macugen. Therefore, IOP as well as the perfusion of the optic nerve head should be monitored and managed appropriately.
Rare cases of anaphylaxis/anaphylactoid reactions, including angioedema, have been reported in postmarketing experience following the intravitreal administration procedure.
Serious adverse events related to the injection procedure occurring in less than 1% of intravitreal injections included endophthalmitis, retinal detachment, and iatrogenic traumatic cataract.
Most frequently reported adverse events in patients treated for up to two years were anterior chamber inflammation, blurred vision, cataract, conjunctival hemorrhage, corneal edema, eye discharge, eye irritation, eye pain, hypertension, increased IOP, ocular discomfort, punctate keratitis, reduced visual acuity, visual disturbance, vitreous floaters, and vitreous opacities. These events occurred in approximately 10% to 40% of patients.
About Eyetech Inc.
Eyetech Inc. is a unique, independent 100% employee-owned and operated biotechnology company dedicated exclusively to the treatment of sight-threatening diseases of the retina. For more information about Eyetech, please visit www.eyetech.com.
(1) Klein R, Klein BE, Moss SE: Visual impairment in diabetes. Ophthalmology 1984; 91: 1-9.
(2) Macugen Diabetic Retinopathy Study Group. "A Phase II Randomized Double-Masked Trial of Pegaptanib, an Anti-Vascular Endothelial Growth Factor Aptamer, for Diabetic Macular Edema." Ophthalmology, Volume 112, Number 10, October 2005.
(3) International Diabetes Federation. Facts Sheet Diabetes and Eye Disease. Available at http://www.idf.org/fact-sheet-diabetes-and-eye-disease. Accessed April 14, 2010.
(5) American Academy of Ophthalmology. "Understanding Diabetic Retinopathy. A Science Writers Guide to a Potentially Blinding Disease." 2006;13.