[There are still studies being conducted on Macugen, but a measure of Macugen’s increasing irrelevance in the AMD arena is that trial designers are opting to avoid including Macugen arms for fear that patients won’t enroll (#msg-10952861). Another measure of Macugen’s irrelevance: PFE never talks about Macugen anymore on investor presentations.]
>> OSI Pharmaceuticals Summarizes Macugen(R) (pegaptanib sodium injection) Data Presented at Association for Research in Vision and Ophthalmology (ARVO) Meeting
Thursday May 4, 2:30 pm ET
NEW YORK--(BUSINESS WIRE)--May 4, 2006--OSI Pharmaceuticals, Inc. (NASDAQ: OSIP ) today provided an informational update summarizing highlights from presentations made regarding Macugen® (pegaptanib sodium injection) at this year's Association for Research in Vision and Ophthalmology (ARVO) annual meeting held from April 30 to May 4 in Fort Lauderdale, Florida. Two preliminary studies that examine the sequential use of a non-selective anti-VEGF (vascular endothelial growth factor) therapy followed by Macugen therapy to address long-term safety and clinical benefit considerations for patients with neovascular age-related macular degeneration (AMD) showed promising indications of activity. Another study provides support to the hypothesis that Macugen may be more effective as primary therapy in neovascular AMD patients with early lesions. Additional presentations included studies of Medicare data, which show that patients over age 65 with neovascular AMD have significantly more co-morbid conditions such as hypertension, diabetes, lipid disorders, stroke and heart attack, compared to those who do not have neovascular AMD. Promising early data demonstrating the potential utility of Macugen in the treatment of diabetic retinopathy, a common debilitating complication of diabetes that can lead to blindness, was also presented.
Following are summaries of select presentations:
Sequential Use of Macugen with Non-selective Anti-VEGF Therapies
Intravitreal Bevacizumab (Avastin®) Enhanced Pegaptanib (Macugen) Therapy for Choroidal Neovascularization in AMD: An Avastin Booster, presented by Michael Tolentino, MD, Center for Retina and Macular Disease, FL.
• Twenty-six eyes of 26 patients received one intravitreal injection of Macugen for neovascular AMD, followed two to three weeks later by one intravitreal injection of bevacizumab (Avastin) and at least two subsequent injections of Macugen. Gains or loss of lines on Snellen acuity between vision prior to Avastin injection and vision prior to the third Macugen injection was used as the primary endpoint. • 9/26 (34.6 percent) eyes gained three lines or more of vision, 18/26 (69.2 percent) eyes gained one or more lines of vision, 5/26 (19.2 percent) eyes had stable vision, and 3/26 (11.5 percent) eyes lost one or more lines of vision.
Safety and Efficacy of Combined Pegaptanib/Bevacizumab Intravitreal Injection as a Treatment for Age-Related Macular Degeneration, presented by Mark Hughes, MD, Ophthalmic Consultants of Boston.
• Twenty patients with a cross section of angiographic subtypes of neovascular AMD were treated with Avastin followed by Macugen. All had one intravitreal injection of Avastin followed by four Macugen injections every six weeks. Four subjects (20 percent) were given an additional intravitreal Avastin injection at week 18. Gains or loss of lines on Snellen acuity was used as the primary endpoint. • The study showed that patients achieved clinically meaningful responses as determined by visual acuity, dilated funduscopy, fundus fluorescein angiography (FFA) and optical coherence tomography (OCT). • After 24 weeks, 7/20 (35 percent) patients gained three lines or more of vision and 20/20 (100 percent) had stabilized vision or gained at least one line of vision. Significant improvements were also made in macular edema as measured by OCT.
These promising preliminary results suggest that further studies are needed to investigate this treatment approach which may take advantage of the long-term safety profile of Macugen while a non-selective anti-VEGF therapy is used initially or as a booster for added clinical benefit.
OSI and Pfizer are planning to initiate a Phase IV trial that will further examine the efficacy of Macugen in patients with neovascular AMD who have previously been treated with different therapies that have resulted in a clinically significant and measurable reduction of macular edema. The trial is scheduled to begin in the second half of 2006 and intends to enroll up to 1,000 patients at 100 sites.
Macugen as Primary Therapy in Neovascular AMD Patients with Early Lesions
Macugen as Primary Therapy for AMD Lesions of All Angiographic Subtypes, presented by Polly Quiram, MD, and colleagues at Associated Retinal Consultants, Beaumont Hospital, MI. A retrospective review of patient data in 90 newly diagnosed neovascular AMD patients undergoing treatment with Macugen as primary therapy showed:
• Ninety percent (81/90) of patients had stabilization or improved vision: 20 percent (18/90) gained => 3 lines of Snellen visual acuity and 70 percent (63/90) had stabilized vision (defined as no change +/- 2 lines). • Only 10 percent (9/90) of patients reported loss of => 3 lines of vision. • This study suggests that Macugen is effective as primary treatment for new neovascular AMD lesions of any angiographic subtype.
Increased Risk of Co-morbid Conditions in Wet AMD Patients
Comparison of Co-morbid Conditions Between Wet AMD Patients and a Control Cohort in the Medicare Population, presented by Sonali Shah, RPh, MBA, MPH, Pfizer Inc. A retrospective analysis of 35,000 Medicare patient reimbursement claims from 2003 found that as compared to the control group, neovascular AMD patients had:
• 31.5 percent higher risk of hypertension • 9.8 percent higher risk of diabetes • 36.4 percent higher risk of lipid disorders • 11.6 percent higher risk of stroke • 22.3 percent higher risk of gastro-intestinal disorders • 11.4 percent higher risk of depression
Association Between Neovascular Age-Related Macular Degeneration and Incidence of Myocardial Infarction (MI), presented by Ingrid Scott, MD, MPH, Penn State College of Medicine. A retrospective review of Medicare reimbursement claims from 2000 to 2003 found that neovascular AMD is associated with a higher risk of myocardial infarction, or heart attack, independent of demographic factors and other co-morbid conditions.
These data suggest that safety is an important consideration when treating neovascular AMD since patients are typically over the age of 65 and are already at risk for cardiovascular and thromboembolic diseases.
Macugen Study in Diabetic Retinopathy Patients
Use of Pegaptanib Sodium (Macugen) for Regression of Proliferative Diabetic Retinopathy, presented by Victor Gonzalez, MD, Valley Retina Institute, TX. Ten patients with proliferative diabetic retinopathy were administered an intravitreal injection of 0.3 mg Macugen every six weeks. Results showed that:
• All 10 eyes injected with Macugen had a marked regression of neovascularization within the first three weeks of treatment. • In addition, there was a decrease in central retinal thickness, also within the first three weeks, without significant adverse events.
These preliminary findings suggest that selective VEGF blockade with Macugen may reduce the progression of proliferative diabetic retinopathy and provide beneficial effects in preventing severe vision loss due to proliferative diabetic retinopathy, but further studies will be needed to confirm and evaluate these effects. The preliminary data also suggest that selective VEGF blockade may allow for less laser therapy, a destructive intervention that can lead to irreversible side-effects, in treating diabetic retinopathy. <<
Though the Lucentis & Regeneron VEGF TRAP P1 trials are different in AMD, I like REGN's efficacy data and the fact that REGN might include Lucentis as control arm in P3.
PS:Single doses of the VEGF Trap were generally well tolerated at all dose levels tested (0.05 to 4 mg), with no systemic or serious adverse events reported. Dose escalation to the highest planned dose was achieved without reaching a maximum tolerated dose (MTD).
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