Encouraging New Data on VEGF-Trap
AMD Patients Show Vision Gains.
Regeneron Pharmaceuticals, Inc. and Bayer HealthCare AG have announced positive preliminary data from an interim analysis of a phase 2 randomized study of their antiangiogenic agent VEGF Trap-Eye in patients with wet AMD.
The 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 from baseline in visual acuity, a key secondary endpoint of the study, also demonstrated statistically significant improvement (all groups combined, increase of 5.9 letters, P<.0001). Moreover, patients in the dose groups that received only a single dose, on average, demonstrated a decrease in excess retinal thickness and an increase in visual acuity at 12 weeks. There were no drug-related serious adverse events, and treatment with the VEGF Trap-Eye was generally well-tolerated. The most common adverse events were those typically associated with intravitreal injections.
The phase 2 study is a 12-week, multicenter trial involving 150 patients who are randomized to 5 groups and treated with the VEGF Trap-Eye in 1 eye. Two groups received either 0.5 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 are monitored for safety, retinal thickness, and visual acuity (VA) over 12 weeks. Retinal thickness is determined by optical coherence tomography (OCT) scans read at an independent reading center. VA is defined as the total number of letters read correctly on the Early Diabetic Retinopathy Study (ETDRS) chart. Maintenance of vision is defined as losing fewer than 3 lines (equivalent to 15 letters) on the ETDRS chart.
The pre-planned interim analysis was conducted on the first 78 patients who completed 12 weeks of study. As summarized above, overall, patients had a statistically significant improvement in retinal thickness and VA. All but 1 patient maintained or improved vision at 12 weeks. Although the improvement in VA was numerically larger in patients receiving injections every 4 weeks, there were no statistically significant differences across the 5 dose groups in either retinal thickness or VA at 12 weeks.
Regeneron said more detailed results from the study will be released in the near future.
These data support our efforts to develop the VEGF Trap as a potent blocker of VEGF in various diseases, said George D. Yancopoulos, MD, PhD, president of Regeneron Research Laboratories. Importantly, the VEGF Trap-Eye may offer the potential to improve vision in patients with wet AMD with dosing less frequently than every 4 weeks. Our phase 3 program is being designed to test this possibility and further evaluate the safety and efficacy of various doses and dosing intervals of the VEGF Trap-Eye.
Though VEGF Trap-Eye is still at least 3 years away from possible approval as a treatment for wet AMD, its mechanism of action is intriguing. The drug creates a decoy receptor that fools VEGF into binding with the decoy and then being converted into a harmless soluble complex. Hence the name VEGF Trap.
VEGF Trap-Eye has potential advantages in that it binds VEGF at a far higher rate than Lucentis, it probably can be safely given in much higher doses than Lucentis, and its effects may be longer-lasting than Lucentis, says Dr. Yancopolous. Of course, these theories will have to be proven in clinical trials but we have already safely given a 4 mg dose of VEGF Trap-Eye to patients, which is 8 times higher than the approved Lucentis dose.
Based on these results, Regeneron and Bayer HealthCare AG plan to initiate the VEGF Trap-Eye phase 3 program in the second half of 2007. The companies are collaborating on the global development of the 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 the VEGF Trap-Eye outside the United States. Regeneron maintains exclusive rights to the drug within the United States.
Retina Fellows Gather to Meet and Learn
Seventh Fellows Forum Adds AMD Session.
Seventy senior vitreoretinal fellows recently gathered in Chicago at the 7th Annual Retina Fellows Forum, a weekend program that gave attendees an opportunity to meet their peers, hear from companies that provide vital products and services, and receive professional advice from leading retina specialists.
New this year was a Friday evening session devoted to the current management of AMD.
Carl C. Awh, MD, of Retina-Vitreous Associates, Nashville, Tenn, served as Course Director. Course co-directors were David Chow, MD, and Tarek Hassan, MD. Bausch & Lomb served as the major corporate sponsor, along with 15 additional sponsors representing a cross-section of industry. Dr. Awh says the overall mission of the program is to provide an expenses-paid educational and social opportunity for all North American vitreoretinal fellows in their final year of training.
The fellows benefit by the opportunity to interact with the entire graduating class of their professional peers, by introduction to representatives of companies that provide vital devices and services, and by participating in academic sessions devoted to the major clinical challenges they will face in practice. We also spend time discussing practice management issues relevant to new practitioners, notes Dr. Awh.
This year, the fellows heard formal presentations on such topics as surgical and medical management of diabetic retinopathy, 25-g and 23-g vitrectomy, treatment of retinal detachment, practice pearls, highlights from the American Society of Retina Specialists Practices and Trends survey, and new instrumentation.
Of note is that the entire faculty is assembled on stage throughout the meeting and each speaker acts as a moderator to solicit opinions from the faculty and the fellows, says Dr. Awh. We use an electronic audience response system to allow immediate feedback from the audience and faculty.
Harry Flynn, MD, (center), Retina Fellows Forum Distinguished Guest Lecturer, with Course Directors Carl Awh, MD, (left) and Tarek Hassan, MD, (right).
The special session on AMD reflects the huge amount of interest in new treatments that are now allowing retina specialists to improve the vision of patients with wet AMD.
We felt that the area of AMD deserved more time than we had been able to devote to it with our traditional 1-day meeting, remarked Dr. Awh. We were able to secure additional support from Genentech to make the AMD symposium possible. It was well-received and we hope to continue this session at future meetings.
It was also announced at the Fellows Forum that Retinal Physician plans to run a regular column written by retina fellows and that the writers would be chosen as a result of a competition. The column will focus on the day-to-day experiences of retina fellows as they progress in their profession.
The Fellows Forum is designed in part to expose fellows to devices and equipment that may not be used in their training program.
I feel that a broader awareness of the range of devices and equipment is of educational value to physicians preparing to start practice, says Dr. Awh. We were fortunate to find a major sponsor, Bausch & Lomb, willing to allow competing companies to exhibit and present at the meeting. Its a nice opportunity for the companies to present themselves to the fellows, and its great for the fellows to be at the center of attention.
A closing dinner and the Second Annual Fellows Forum Bowling tournament, won by a team captained by Diana Do, MD, topped off the weekend.
In addition to Drs. Do, Chow, Hassan and Awh, Fellows Forum faculty included Brandon Busbee, MD, Thomas Chang, MD, John Pollack, MD, and Peter Kaiser, MD. Harry Flynn, MD, of the Bascom Palmer Eye Institute in Miami, was the Distinguished Guest Lecturer.
The 8th Annual Fellows Forum will be held in Chicago the weekend of Jan. 26, 2008.