OSI Pharmaceuticals, Inc. and Pfizer Inc. announced the initiation of LEVEL (EvaLuation of Efficacy and safety in maintaining Visual acuity with sEquential treatment of neovascuLar AMD), a phase IV trial that will explore the safety and efficacy of Macugen (pegaptanib sodium injection) as a maintenance therapy for patients who have received prior neovascular AMD treatment and experienced improvement in macular disease. The 54-week trial, comprising up to 1000 patients at 100 sites across the country, is scheduled to enrol its first patient.

Neovascular AMD is a chronic, progressive disease that may require ongoing management. Nearly 70,000 patients have already been treated with Macugen, which offers proven efficacy and safety for up to two years in the treatment of neovascular AMD with six-week dosing. Safety may be an important consideration when choosing a maintenance therapy.

According to retrospective Medicare data presented at the annual meeting of the Association for Research in Vision and Ophthalmology, patients with neovascular AMD are typically older, with significantly more co-morbid conditions such as hypertension, diabetes, lipid disorders, stroke and heart attack than those who do not have neovascular AMD.

"Armed with a growing number of treatment options, we should explore new regimens that may be capable of providing beneficial patient outcomes while addressing long-term safety and dosing considerations," said Thomas R. Friberg, MS, MD, Professor of Ophthalmology and Bioengineering University of Pittsburgh Medical Center and a lead investigator in the LEVEL trial. "For example, clinical data suggest that a non-selective anti-VEGF-A therapy can improve vision in a significant portion of patients and that this improvement may stabilize after a few injections. It makes sense to study whether these gains can also be maintained using a selective anti-VEGF therapy."

Neovascular AMD research suggests that the chronic suppression of VEGF (vascular endothelial growth factor) may be important in minimizing the risk of recurrent macular swelling and bleeding that may result in irreversible vision loss. By specifically targeting and suppressing VEGF 165, Macugen has been shown to reduce blood vessel growth and preserve vision by slowing vision loss. In addition, Macugen has an excellent long-term safety profile that has been evaluated in controlled clinical trials up to two years. Patients were then followed for a third year of treatment in an uncontrolled extension study.

"The introduction of anti-VEGF therapy marked a new era in the management of neovascular AMD, yet we still have much to learn," said Anthony P. Adamis, M.D., Chief Scientific Officer, (OSI) Eyetech. "Macugen has proven efficacy and safety. The LEVEL trial will provide further insight into Macugen's potential role in new treatment regimens for neovascular AMD."

In this open label, multi-center trial, subjects must have had at least one, but no more than three treatments for neovascular AMD within 30 to 120 days prior to study entry leading to an improvement in macular disease. Macugen will be administered once every six weeks for 48 weeks. Booster treatment with additional neovascular AMD therapy may be employed if the investigator believes macular disease has progressed.

The primary endpoint is the percentage of subjects who remain at baseline vision or gain (greater than or equal to 0 lines) vision from baseline to 54 weeks. Secondary endpoints include the percentage of subjects maintaining or gaining one, two and three lines of visual acuity at week 54 compared to pre-enrolment baseline vision (treatment initiation baseline); the mean change of visual acuity from baseline to Week 54; the percentage of subjects losing less than three lines of vision at 54 weeks; and anatomical outcomes on fluorescein angiography and optical coherence tomography.

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 per cent of blindness caused by the disease.

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.

Macugen has been approved by regulatory authorities in the United States, European Union, Canada, Brazil, Argentina, Peru, Pakistan, the Philippines and Switzerland, with filings submitted in 14 other countries. OSI and Pfizer Inc. co-promote Macugen in the United States. OSI has granted Pfizer the exclusive rights to commercialize Macugen in countries outside the United States pursuant to a royalty-bearing licensing agreement. Macugen is now available in the United States, Canada, United Kingdom, Germany, Sweden, Finland, Ireland, Austria, Philippines and Pakistan.