VEGF Trap Moving to Phase 3 Trials
AMD and DME Studies Show Efficacy.
■ Regeneron Pharmaceuticals, Inc., is initiating a phase 3 trial for VEGF Trap-Eye after announcing positive results from studies evaluating the drug in wet AMD and diabetic macular edema (DME). The findings were presented recently at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO).
"We are very encouraged by the preliminary observation in the phase 2 wet AMD trial that the most intense dosing regimen studied, 2 mg delivered by intravitreal injection every 4 weeks, resulted in an average gain of more than 10 letters after 12 weeks of treatment," said George D. Yancopoulos, MD, PhD, president of Regeneron Research Laboratories.
"Perhaps equally important is that after receiving only a single dose of VEGF Trap-Eye, patients on average had an improvement (above baseline) in the number of letters read at both 8 and 12 weeks after treatment (with the peak in vision improvement occurring between the fourth and eighth weeks). Although significantly more clinical testing is required, VEGF Trap-Eye may offer the potential to improve vision in patients with wet AMD with a regular dosing regimen that is less frequent than monthly."
Regeneron and its partner Bayer HealthCare AG plan to initiate the VEGF Trap-Eye phase 3 study in wet AMD this summer. In the first phase 3 trial, the companies currently plan to evaluate VEGF Trap-Eye using 4- and 8-week dosing intervals in direct comparison with ranibizumab (Lucentis) administered every 4 weeks according to its label. The 2 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 AG and Regeneron will jointly commercialize VEGF Trap-Eye outside the United States, while Regeneron maintains exclusive rights within the United States.
|"After a single dose, vision still showed improvement at 12 weeks."|
In the phase 2 wet AMD trial, additional new data were presented from a pre-planned interim analysis of the first 78 patients who completed 12 weeks of the study. The randomized, multicenter trial involves 150 patients who were randomized to 5 groups and treated with VEGF Trap-Eye in 1 eye.
Two groups received either 0.5 mg or 2 mg of VEGF Trap-Eye administered every 4 weeks, and 3 groups received a single dose of 0.5, 2, or 4 mg of VEGF Trap-Eye. Patients were monitored for safety, retinal thickness, and visual acuity over 12 weeks. VEGF Trap-Eye met its primary endpoint of a statistically significant reduction in retinal thickness after 12 weeks compared with baseline (all groups combined, decrease of 135 μm, P<.0001). Mean change in visual acuity, a key secondary endpoint of the study, also demonstrated a statistically significant improvement (all groups combined, increase of 5.9 letters, P<.0001). There were no drug-related serious adverse events, and treatment with VEGF Trap-Eye was generally well tolerated. The most common adverse events were those typically associated with intravitreal injections. Interim data for all dose groups were presented at the ARVO meeting. The phase 2 wet AMD study is now fully enrolled and results for all patients will be presented at a future scientific meeting.
Encouraging results were also presented from a phase 1 study of VEGF Trap-Eye in DME. In this open-label safety study, VEGF Trap-Eye was administered as a single 4 mg intravitreal injection to 5 patients with longstanding diabetes and multiple prior treatments for DME. The single injection resulted in a marked decrease in mean central retinal thickness and mean macular volume throughout the 6-week observation period. The VEGF Trap-Eye was generally well tolerated and there were no drug-related serious adverse events. Adverse events were mostly related to the injection procedure.
|■ Lucentis sales stay firm. Genentech reported that first-quarter 2007 sales of its wet AMD treatment Lucentis totaled $211 million, almost matching the record $217 million in Lucentis sales in the final quarter of 2006. Lucentis, which was approved by the FDA last June, has quickly established itself as the leading drug for the treatment of wet AMD.|
■ Spectral-domain OCT. Heidelberg Engineering GmbH, a leading developer of laser diagnostics for ophthalmic applications, said the FDA has granted clearance for the Spectralis Heidelberg Retinal Angiograph (HRA)+OCT, the world's first commercial spectral-domain OCT combined with laser angiography.
Heidelberg says the Spectralis detects previously unrecognized structures, combining high-resolution, cross-sectional images of the retina with any of 4 imaging modalities: autofluorescence, infrared, fluorescein angiography, or ICG angiography. Heidelberg says the new device scans the retina 100 times faster than time-domain OCT.
The Spectralis spectral-domain system, sometimes called Fourier domain, scans the retina at 40000 scans per second, creating highly detailed images of the structure of the retina. Because the OCT and HRA images are captured simultaneously, the clinician can be assured of the exact location of the area of interest and can correlate the outer visible retina structure with the internal structure.
"This new technology represents a dramatic leap in our ability to image complex macular disease," says Scott Cousins, MD, director, Duke Center for Macular Diseases at Duke University. "The combination of these two cutting-edge technologies will amplify our understanding of retinal structure and provide us with new insights into the biological processes of the retina."
The Spectralis will be presented at the American Academy of Ophthalmology meeting in November. The company expects to begin shipping the product this summer.
■ Visudyne sales stabilize. QLT Inc. said sales of its wet AMD therapy Visudyne were approximately $8.4 million in the first 3 months of 2007.
"Sales of Visudyne in the United States appear to have stabilized in January and grew in February and March due to increases in market share of combination therapy," said Bob Butchofsky, president and CEO of QLT Inc., which developed Visudyne in partnership with Novartis. "Visudyne average daily sales were 105 vials in January, but average daily sales increased in both February and March to 116 and 130 vials, respectively." RP