Regeneron Pharmaceuticals, Inc. announced that the company submitted a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) for VEGF Trap-Eye for the treatment of the neo-vascular form of Age-related Macular Degeneration (wet AMD). Under the Prescription Drug User Fee Act (PDUFA), the goal for a standard review time from submission to FDA action is ten months. Regeneron's submission includes a request for Priority Review, which, if granted, would shorten the FDA's targeted goal for review time under PDUFA to six months.
“There have been significant advances in the treatment of wet AMD in recent years. However, the need for monthly intravitreal injections to obtain optimal vision gains has resulted in a significant burden for physicians, patients, and their caregivers,” said Leonard S. Schleifer, MD, PhD, president and CEO of Regeneron. “We are extremely proud to have conducted the largest global phase III clinical programme in patients with wet AMD, which demonstrated that patients treated with VEGF Trap-Eye 2 mg every two months, following three loading doses, were able to be dosed with fewer injections over one year without compromising efficacy. We look forward to working closely with the FDA to bring this potentially important new medicine to patients with wet AMD.”
The VEGF Trap-Eye BLA is based on the positive results from two phase III trials, the North American VIEW 1 trial and the global VIEW 2 trial. In these trials, all regimens of VEGF Trap-Eye, including VEGF Trap-Eye dosed 2 milligrams (mg) every two months (following three loading doses), successfully met the primary endpoint of non-inferiority, compared to the current standard of care, ranibizumab 0.5 mg dosed every month.
The primary endpoint analysis was statistical non-inferiority in the proportion of patients who maintained (or improved) vision over 52 weeks compared to ranibizumab. A generally favourable safety profile was observed for both VEGF Trap-Eye and ranibizumab. The ocular adverse events were balanced across all treatment groups in both studies. There were no notable differences in non-ocular adverse events among the study arms.
The VIEW (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD) programme consists of two randomized, double-masked, phase III clinical trials evaluating VEGF Trap-Eye in the treatment of the neo-vascular form of Age-related Macular Degeneration (wet AMD). The study, which randomized 1217 patients, is being conducted in the United States and Canada by Regeneron under a Special Protocol Assessment (SPA) with the US Food and Drug Administration.
The second study, which randomized 1240 patients, is being conducted in Europe, Asia Pacific, Japan, and Latin America by Bayer HealthCare. The study designs are essentially identical. The primary endpoint evaluation was conducted at 52 weeks.
In each of the studies, VEGF Trap-Eye was evaluated for its effect on maintaining and improving vision when dosed as an intravitreal injection on a schedule of 0.5 mg monthly, 2.0 mg monthly, or 2.0 mg every two months (following three monthly loading doses), as compared with intravitreal ranibizumab administered 0.5 mg every month during the first year of the studies.
The primary endpoint of these non-inferiority studies was the proportion of patients treated with VEGF Trap-Eye who maintained visual acuity at the end of one year, compared to ranibizumab patients. Visual acuity was measured as a score based on the total number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart, a standard chart used in research to measure visual acuity.
VEGF Trap-Eye is a fusion protein consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 that binds all forms of VEGF-A, along with the related Placental Growth Factor (PlGF). VEGF Trap-Eye is a specific and highly potent blocker of these growth factors. VEGF Trap-Eye is specially purified and contains iso-osmotic buffer concentrations, allowing for injection into the eye.
Regeneron and Bayer HealthCare are collaborating on the development of VEGF Trap-Eye for the treatment of wet AMD, central retinal vein occlusion, diabetic macular edema, myopic choroidal neovascularisation, and other eye diseases and disorders. Bayer HealthCare intends to submit regulatory applications in the first half of 2011 for marketing approval in Europe. If approved by regulatory authorities, Bayer HealthCare will market VEGF Trap-Eye outside the United States, where the companies will share equally in profits from any future sales of VEGF Trap-Eye. Regeneron maintains exclusive rights to VEGF Trap-Eye in the United States.
Age-related Macular Degeneration (AMD) is a leading cause of acquired blindness. Macular degeneration is diagnosed as either dry (non-exudative) or wet (exudative). In wet AMD, new blood vessels grow beneath the retina and leak blood and fluid. This leakage causes disruption and dysfunction of the retina creating distortion and/or blind spots in central vision and it can account for blindness in wet AMD patients. Wet AMD is the leading cause of blindness for people over the age of 65 in the US and Europe. It is estimated that more than 210,000 Americans are newly diagnosed with and treated for wet AMD each year.
Over 100,000 people in the United States and more than 66,000 people in key European countries are estimated to suffer from central retinal vein occlusion (CRVO). CRVO is caused by obstruction of the central retinal vein that leads to a back up of blood and fluid in the retina. This causes retinal injury and loss of vision. The retina can also become “ischemic” (starved for oxygen), resulting in the growth of new, inappropriate blood vessels that can cause further vision loss and more serious complications.
Release of Vascular Endothelial Growth Factor (VEGF) contributes to increased vascular permeability in the eye and inappropriate new vessel growth. It is believed that anti-VEGF treatment may help decrease vascular permeability and edema and prevent the inappropriate growth of new blood vessels in the retina in patients with CRVO.
Diabetic Macular Edema (DME) is the most prevalent cause of moderate vision loss in patients with diabetes. DME is a common complication of Diabetic Retinopathy (DR), a disease affecting the blood vessels of the retina. Clinically significant DME is a leading cause of blindness in younger adults (under 50). Clinically significant DME occurs when fluid leaks into the center of the macula, the light-sensitive part of the retina responsible for sharp, direct vision. Fluid in the macula can cause severe vision loss or blindness.
Approximately 370,000 Americans currently suffer from clinically significant DME, with 95,000 new cases arising each year. According to the American Diabetes Association, more than 18 million Americans currently suffer from diabetes, and many other people are at risk for developing diabetes. With the incidence of diabetes steadily climbing, it is projected that up to 10 percent of all patients with diabetes will develop DME during their lifetime.
Regeneron is a fully integrated biopharmaceutical company that discovers, develops, and commercializes medicines for the treatment of serious medical conditions. In addition to Arcalyst (rilonacept) Injection for Subcutaneous Use, its first commercialized product, Regeneron has therapeutic candidates in phase III clinical trials for the potential treatment of gout, diseases of the eye (wet age-related macular degeneration and central retinal vein occlusion), and certain cancers.