Regression of total active lesion caused by wet AMD reported
SCOTTSDALE, AZ, USA | September 28, 2008 | Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) and Bayer HealthCare AG announced that VEGF Trap-Eye achieved durable improvements in visual acuity and in biologic measures of neovascular disease, including retinal thickness and active choroidal neovascularization lesion size, for up to one year in a Phase 2 study in the neovascular form of Age-related Macular Degeneration (wet AMD). The results were reported today in two oral presentations at the 2008 annual meeting of the Retina Society in Scottsdale, Arizona. Slides, including data reported at the presentations, are available on the Regeneron website (www.regeneron.com on the Presentations Page, under the Investor Relations section).
In this double-masked Phase 2 trial, patients were initially treated with either fixed monthly or quarterly dosing for 12 weeks and then continued to receive treatment for another 40 weeks on a PRN (as needed) dosing schedule. Patients receiving monthly doses of VEGF Trap-Eye of either 2.0 or 0.5 milligrams (mg) for 12 weeks followed by PRN dosing achieved mean improvements in visual acuity versus baseline of 9.0 letters (p<0.0001 versus baseline) and 5.4 letters (p<0.085 versus baseline), respectively, at the end of one year. The proportion of patients with vision of 20/40 or better (part of the legal minimum requirement for an unrestricted driver’s license in the U.S.) increased from 23 percent at baseline to 45 percent at week 52 in patients initially treated with 2.0 mg monthly and from 16 percent at baseline to 47 percent at week 52 in patients initially treated with 0.5 mg monthly. During the week 12 to week 52 PRN dosing period, patients initially dosed on a 2.0 mg monthly schedule received, on average, only 1.6 additional injections and those initially dosed on a 0.5 mg monthly schedule received, on average, 2.5 injections.
Patients receiving monthly doses of VEGF Trap-Eye of either 2.0 or 0.5 mg for 12 weeks followed by PRN dosing also achieved mean decreases in retinal thickness versus baseline of 143 microns (p<0.0001 versus baseline) and 125 microns (p<0.0001 versus baseline) at week 52, respectively.
While PRN dosing following a fixed quarterly dosing regimen (with dosing at baseline and week 12) also yielded improvements in visual acuity and retinal thickness versus baseline at week 52, the results generally were not as robust as those obtained with initial fixed monthly dosing.
"Anti-VEGF therapy has dramatically changed the treatment paradigm for wet AMD, and improvement in visual acuity is now feasible in most patients. The biggest challenge we have is that with our current drugs, the majority of patients need frequent injections into their eye to maintain their visual acuity gains," stated David M. Brown, M.D., a study investigator and a retinal specialist at The Methodist Hospital in Houston. "These study results reinforce our interest in further exploring whether continued administration of VEGF Trap-Eye on an as-needed basis after an initial period of fixed dosing can maintain a durability of effect over time in controlled Phase 3 clinical studies."
In this Phase 2 study VEGF Trap-Eye was also associated with a reduction in the size of the total active choroidal neovascular membrane (CNV), the active lesion that is the underlying cause of vision loss in patients with wet AMD. Patients initially receiving either a 2.0 mg or 0.5 mg monthly fixed dose of VEGF Trap-Eye for 12 weeks followed by PRN dosing experienced statistically significant 3.41 mm(2) and 1.42 mm(2) reductions in mean CNV size at 48 weeks (the final one-year analysis from the independent reading center) versus baseline, respectively. Patients in the 2.0 mg monthly cohort also achieved a statistically significant 1.75 mm(2) reduction in total lesion size. A reduction in total lesion size was not seen in the cohort initially dosed with 0.5 mg monthly.
"Progression of the active CNV lesion and resulting vision impairment are inevitable consequences of untreated wet AMD. The reduction in total active CNV lesion size achieved with VEGF Trap-Eye treatment in this Phase 2 clinical study could potentially translate into clinically meaningful outcomes in the larger, controlled Phase 3 studies that are underway," stated Jason Slakter, M.D., head of the independent reading center for the study and a Clinical Professor of Ophthalmology, New York University School of Medicine, New York.
VEGF Trap-Eye was generally well tolerated and there were no drug-related serious adverse events. There was one reported case of culture-negative endophthalmitis/uveitis in the study eye, which was deemed not to be drug-related. The most common adverse events were those typically associated with intravitreal injections.
"These study results confirm the rationale for our Phase 3 clinical program for VEGF Trap-Eye in wet AMD," said George D. Yancopoulos, M.D., Ph.D., President of Regeneron Research Laboratories. "These trials are designed to optimize improvement in visual acuity with fixed-dosing regimens of either every 4 weeks or every 8 weeks for one year and then study how these vision improvements can be maintained with as-needed dosing in the second year."
About the Phase 2 Study in Wet AMD
In the double-masked, prospective, randomized, multi-center Phase 2 trial, 157 patients were randomized to five dose groups and treated with VEGF Trap-Eye in one eye. Two groups initially received monthly doses of 0.5 or 2.0 milligrams (mg) of VEGF Trap-Eye (at weeks 0, 4, 8, and 12) and three groups received quarterly doses of 0.5, 2.0, or 4.0 mg of VEGF Trap-Eye (at baseline and week 12). Following the initial 12-week fixed-dosing phase of the trial, patients continued to receive therapy at the same dose on a PRN dosing schedule based upon the physician assessment of the need for re-treatment in accordance with pre-specified criteria. Patients were monitored for safety, retinal thickness, and visual acuity. The primary endpoint results from the fixed dosing period were presented at the 2007 Retina Society conference in September 2007. Week 32 results were presented at the 2008 Association for Research in Vision and Ophthalmology annual meeting in April 2008.
About the Phase 3 Program in Wet AMD
Regeneron and Bayer HealthCare initiated a Phase 3 global development program for VEGF Trap-Eye in wet AMD in August 2007. In two Phase 3 trials, the companies are evaluating VEGF Trap-Eye dosed 0.5 mg every 4 weeks, 2 mg every 4 weeks, or 2 mg every 8 weeks (following three monthly doses) in direct comparison with ranibizumab (Lucentis(R), a registered trademark of Genentech, Inc.) administered 0.5 mg every 4 weeks according to its U.S. label during the first year of the studies. PRN dosing will be evaluated during the second year of each study. The VIEW1 study is currently enrolling patients in the United States and Canada and the VIEW2 study is currently enrolling patients in Europe, Asia Pacific, Japan, and Latin America. The companies are collaborating on the global development of VEGF Trap-Eye for the treatment of wet AMD, diabetic eye diseases, and other eye diseases and disorders. 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.
About VEGF Trap-Eye
Vascular Endothelial Growth Factor (VEGF) is a naturally occurring protein in the body whose normal role is to trigger formation of new blood vessels (angiogenesis) to support the growth of the body’s tissues and organs. It has also been associated with the abnormal growth and fragility of new blood vessels in the eye, which lead to the development of wet AMD. The VEGF Trap-Eye is a fully human, soluble VEGF receptor fusion protein 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. Blockade of VEGF, which can prevent abnormal blood vessel formation and vascular leak, has proven beneficial in the treatment of wet AMD.
About Wet AMD
Age-related Macular Degeneration (AMD) is a leading cause of acquired blindness. Macular degeneration is diagnosed as either dry (nonexudative) 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 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 U.S. and Europe.
About Regeneron Pharmaceuticals, Inc.
Regeneron is a fully integrated biopharmaceutical company that discovers, develops, and commercializes medicines for the treatment of serious medical conditions. In addition to ARCALYST(R) (rilonacept) Injection for Subcutaneous Use, its first commercialized product, Regeneron has therapeutic candidates in clinical trials for the potential treatment of cancer, eye diseases, and inflammatory diseases and has preclinical programs in other diseases and disorders. Additional information about Regeneron and recent news releases are available on Regeneron’s web site at www.regeneron.com.
SOURCE: Regeneron Pharmaceuticals, Inc.
Post Views: 68
Regression of total active lesion caused by wet AMD reported
SCOTTSDALE, AZ, USA | September 28, 2008 | Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) and Bayer HealthCare AG announced that VEGF Trap-Eye achieved durable improvements in visual acuity and in biologic measures of neovascular disease, including retinal thickness and active choroidal neovascularization lesion size, for up to one year in a Phase 2 study in the neovascular form of Age-related Macular Degeneration (wet AMD). The results were reported today in two oral presentations at the 2008 annual meeting of the Retina Society in Scottsdale, Arizona. Slides, including data reported at the presentations, are available on the Regeneron website (www.regeneron.com on the Presentations Page, under the Investor Relations section).
In this double-masked Phase 2 trial, patients were initially treated with either fixed monthly or quarterly dosing for 12 weeks and then continued to receive treatment for another 40 weeks on a PRN (as needed) dosing schedule. Patients receiving monthly doses of VEGF Trap-Eye of either 2.0 or 0.5 milligrams (mg) for 12 weeks followed by PRN dosing achieved mean improvements in visual acuity versus baseline of 9.0 letters (p<0.0001 versus baseline) and 5.4 letters (p<0.085 versus baseline), respectively, at the end of one year. The proportion of patients with vision of 20/40 or better (part of the legal minimum requirement for an unrestricted driver’s license in the U.S.) increased from 23 percent at baseline to 45 percent at week 52 in patients initially treated with 2.0 mg monthly and from 16 percent at baseline to 47 percent at week 52 in patients initially treated with 0.5 mg monthly. During the week 12 to week 52 PRN dosing period, patients initially dosed on a 2.0 mg monthly schedule received, on average, only 1.6 additional injections and those initially dosed on a 0.5 mg monthly schedule received, on average, 2.5 injections.
Patients receiving monthly doses of VEGF Trap-Eye of either 2.0 or 0.5 mg for 12 weeks followed by PRN dosing also achieved mean decreases in retinal thickness versus baseline of 143 microns (p<0.0001 versus baseline) and 125 microns (p<0.0001 versus baseline) at week 52, respectively.
While PRN dosing following a fixed quarterly dosing regimen (with dosing at baseline and week 12) also yielded improvements in visual acuity and retinal thickness versus baseline at week 52, the results generally were not as robust as those obtained with initial fixed monthly dosing.
"Anti-VEGF therapy has dramatically changed the treatment paradigm for wet AMD, and improvement in visual acuity is now feasible in most patients. The biggest challenge we have is that with our current drugs, the majority of patients need frequent injections into their eye to maintain their visual acuity gains," stated David M. Brown, M.D., a study investigator and a retinal specialist at The Methodist Hospital in Houston. "These study results reinforce our interest in further exploring whether continued administration of VEGF Trap-Eye on an as-needed basis after an initial period of fixed dosing can maintain a durability of effect over time in controlled Phase 3 clinical studies."
In this Phase 2 study VEGF Trap-Eye was also associated with a reduction in the size of the total active choroidal neovascular membrane (CNV), the active lesion that is the underlying cause of vision loss in patients with wet AMD. Patients initially receiving either a 2.0 mg or 0.5 mg monthly fixed dose of VEGF Trap-Eye for 12 weeks followed by PRN dosing experienced statistically significant 3.41 mm(2) and 1.42 mm(2) reductions in mean CNV size at 48 weeks (the final one-year analysis from the independent reading center) versus baseline, respectively. Patients in the 2.0 mg monthly cohort also achieved a statistically significant 1.75 mm(2) reduction in total lesion size. A reduction in total lesion size was not seen in the cohort initially dosed with 0.5 mg monthly.
"Progression of the active CNV lesion and resulting vision impairment are inevitable consequences of untreated wet AMD. The reduction in total active CNV lesion size achieved with VEGF Trap-Eye treatment in this Phase 2 clinical study could potentially translate into clinically meaningful outcomes in the larger, controlled Phase 3 studies that are underway," stated Jason Slakter, M.D., head of the independent reading center for the study and a Clinical Professor of Ophthalmology, New York University School of Medicine, New York.
VEGF Trap-Eye was generally well tolerated and there were no drug-related serious adverse events. There was one reported case of culture-negative endophthalmitis/uveitis in the study eye, which was deemed not to be drug-related. The most common adverse events were those typically associated with intravitreal injections.
"These study results confirm the rationale for our Phase 3 clinical program for VEGF Trap-Eye in wet AMD," said George D. Yancopoulos, M.D., Ph.D., President of Regeneron Research Laboratories. "These trials are designed to optimize improvement in visual acuity with fixed-dosing regimens of either every 4 weeks or every 8 weeks for one year and then study how these vision improvements can be maintained with as-needed dosing in the second year."
About the Phase 2 Study in Wet AMD
In the double-masked, prospective, randomized, multi-center Phase 2 trial, 157 patients were randomized to five dose groups and treated with VEGF Trap-Eye in one eye. Two groups initially received monthly doses of 0.5 or 2.0 milligrams (mg) of VEGF Trap-Eye (at weeks 0, 4, 8, and 12) and three groups received quarterly doses of 0.5, 2.0, or 4.0 mg of VEGF Trap-Eye (at baseline and week 12). Following the initial 12-week fixed-dosing phase of the trial, patients continued to receive therapy at the same dose on a PRN dosing schedule based upon the physician assessment of the need for re-treatment in accordance with pre-specified criteria. Patients were monitored for safety, retinal thickness, and visual acuity. The primary endpoint results from the fixed dosing period were presented at the 2007 Retina Society conference in September 2007. Week 32 results were presented at the 2008 Association for Research in Vision and Ophthalmology annual meeting in April 2008.
About the Phase 3 Program in Wet AMD
Regeneron and Bayer HealthCare initiated a Phase 3 global development program for VEGF Trap-Eye in wet AMD in August 2007. In two Phase 3 trials, the companies are evaluating VEGF Trap-Eye dosed 0.5 mg every 4 weeks, 2 mg every 4 weeks, or 2 mg every 8 weeks (following three monthly doses) in direct comparison with ranibizumab (Lucentis(R), a registered trademark of Genentech, Inc.) administered 0.5 mg every 4 weeks according to its U.S. label during the first year of the studies. PRN dosing will be evaluated during the second year of each study. The VIEW1 study is currently enrolling patients in the United States and Canada and the VIEW2 study is currently enrolling patients in Europe, Asia Pacific, Japan, and Latin America. The companies are collaborating on the global development of VEGF Trap-Eye for the treatment of wet AMD, diabetic eye diseases, and other eye diseases and disorders. 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.
About VEGF Trap-Eye
Vascular Endothelial Growth Factor (VEGF) is a naturally occurring protein in the body whose normal role is to trigger formation of new blood vessels (angiogenesis) to support the growth of the body’s tissues and organs. It has also been associated with the abnormal growth and fragility of new blood vessels in the eye, which lead to the development of wet AMD. The VEGF Trap-Eye is a fully human, soluble VEGF receptor fusion protein 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. Blockade of VEGF, which can prevent abnormal blood vessel formation and vascular leak, has proven beneficial in the treatment of wet AMD.
About Wet AMD
Age-related Macular Degeneration (AMD) is a leading cause of acquired blindness. Macular degeneration is diagnosed as either dry (nonexudative) 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 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 U.S. and Europe.
About Regeneron Pharmaceuticals, Inc.
Regeneron is a fully integrated biopharmaceutical company that discovers, develops, and commercializes medicines for the treatment of serious medical conditions. In addition to ARCALYST(R) (rilonacept) Injection for Subcutaneous Use, its first commercialized product, Regeneron has therapeutic candidates in clinical trials for the potential treatment of cancer, eye diseases, and inflammatory diseases and has preclinical programs in other diseases and disorders. Additional information about Regeneron and recent news releases are available on Regeneron’s web site at www.regeneron.com.
SOURCE: Regeneron Pharmaceuticals, Inc.
Post Views: 68
