Phase 3 Study Presented at World Ophthalmology Congress Evaluates Investigational Use of Macugen in Patients with Diabetic Macular Edema

Palm Beach Gardens, FL – June 5, 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.

About Macugen

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.

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.

References

(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.
(4) Ibid.
(5) American Academy of Ophthalmology. “Understanding Diabetic Retinopathy. A Science Writers Guide to a Potentially Blinding Disease.” 2006;13.

LEVEL Study Published in British Journal of Ophthalmology Evaluates Macugen as Maintenance Treatment for Patients with Neovascular Age-Related Macular Degeneration

Link to LEVEL Study: http://bjo.bmj.com/content/early/2010/05/14/bjo.2009.174946.full.html

Link to NewsInfusion: http://www.newsinfusion.com/video_details.php?videoId=489

Palm Beach Gardens, FL – May 18, 2010 – Eyetech Inc. announced today that the British Journal of Ophthalmology (BJO) published online results from the LEVEL study evaluating Macugen™ (pegaptanib sodium) as a maintenance therapy in neovascular age-related macular degeneration (AMD). This large, open-label, uncontrolled, exploratory study enrolled 568 patients who had been treated one to three times for neovascular AMD, primarily with a non-selective VEGF-inhibitor such as ranibizumab or bevacizumab. During this induction phase, the mean visual acuity improved by 15.9 letters (49.6 letters to 65.5 letters). After entering the study, patients were switched to Macugen, a selective VEGF-inhibitor, with the possibility of using additional treatments if needed. At the end of this 54-week maintenance phase, mean final visual acuity was 61.8 letters. From the beginning of the induction phase to the end of maintenance phase, an approximately 16-month follow-up, 41 percent of patients gained at least 3 lines of visual acuity.

The study authors concluded that this induction-maintenance treatment strategy, using non-selective VEGF inhibitors then switching to Macugen, a selective VEGF inhibitor, may be an option for the long-term treatment of neovascular AMD. “A treatment protocol that combines the efficacy of a non-selective VEGF inhibitor with the safety profile of a selective VEGF inhibitor may be an attractive option, since elderly patients with AMD are already at increased risk of hypertension, stroke and other cardiovascular disease,” said Thomas R. Friberg, M.D., lead investigator of the LEVEL study and Professor of Ophthalmology and Bio-Engineering at the University of Pittsburgh.

“This treatment approach may be of particular interest to retina specialists and their AMD patients with cardiovascular co-morbidities who require long-term treatment with anti-VEGF drugs to manage their neovascular AMD,” continued Dr. Friberg. “Unlike non-selective VEGF inhibitors that should be administered monthly, Macugen is administered every six weeks. This substantially reduces the treatment burden on patients and their families.”

Despite the limitations of an uncontrolled study, Macugen when used as a maintenance therapy showed adverse events rates similar to those observed in the pivotal Phase III V.I.S.I.O.N trial at one year. During one year of follow-up, there was no evidence of increased risk of endophthalmitis, retinal detachment of traumatic cataract. Most common ocular adverse events were punctate keratitis, eye pain and vitreous floaters. Reports of serious non-ocular, vascular events (including cardiovascular events) were rare.

About the LEVEL Study

LEVEL (EvaLuation of Efficacy and safety in maintaining Visual acuity with sEquential treatment of neovascuLar AMD) is a Phase IV, prospective, open-label, uncontrolled exploratory study designed to assess the efficacy of Macugen as a maintenance therapy in neovascular AMD patients who had at least one but not more than three prior treatments (induction phase) 30 to 120 days prior to study entry. Patients who showed significant clinical and/or anatomical improvement in their neovascular AMD, as determined by the study investigator, were enrolled in the LEVEL study and administered intravitreal injections of Macugen 0.3 mg every six weeks for 48 weeks with follow-up through week 54.

Additional treatments with other agents were allowed in the study eye at investigators’ discretion for deteriorating AMD. Half of patients (283/568) required an additional treatment during the study, which was given approximately 5 months post-baseline on average. Of those who received an additional treatment, 46% required only one such treatment.

The results from the exploratory trial suggest that this induction/maintenance regimen may be a promising approach in the long-term treatment of neovascular AMD. From the beginning of induction treatment to week 54 of the maintenance phase, 41% of patients gained > 3 lines of vision, 79% gained > 0 lines and 92% lost < 3 lines of vision. Randomized, controlled trials are needed to corroborate the findings of the LEVEL study.

About Age-Related Macular Degeneration (AMD)

AMD is a chronic, progressive disease of the central portion of the retina called the macula, resulting in the loss of central vision. The most common symptoms are a central blurred or blank spot, distortion of objects or simply blurred vision. Peripheral vision usually remains intact. AMD is classified into two forms: atrophic, referred to as dry AMD, and neovascular or wet AMD.

In neovascular AMD, abnormal blood vessels grow and leak into the macula, resulting in loss of vision. Neovascular AMD is the more severe form of the disease and progresses more rapidly than the dry type. Although it accounts for only about 10-15 percent of all macular degeneration cases, neovascular AMD is responsible for 90 percent of blindness caused by the disease.

About Macugen

Macugen, a selective inhibitor of VEGF-165, is indicated 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.

Eyetech Inc. markets and sells Macugen in the United States and Pfizer Inc. markets and sells Macugen outside of the United States. For full prescribing information about Macugen, please visit http://www.macugen.com/.