VEGF-Trap in Second Phase 3 Study
Comparison to Ranibizumab is Sought.
■ The first patient has been dosed in the VIEW 2 trial, a second phase 3 clinical study in a development program evaluating VEGF Trap-Eye for the treatment of wet AMD.
Regeneron Pharmaceuticals and partner Bayer HealthCare said VIEW 2 (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD) will enroll approximately 1200 patients in up to 200 centers in Europe, Asia Pacific, Japan, and Latin America. The first phase 3 trial, VIEW 1, began enrolling patients in August 2007 in the United States and Canada.
Both VIEW 1 and VIEW 2 are designed to evaluate the efficacy and safety of VEGF Trap-Eye administered by intravitreal injection at dosing intervals of 4 weeks and 8 weeks. The development program will include visual acuity and anatomical endpoints, including retinal thickness. The trial is intended to establish non-inferiority of VEGF Trap-Eye with ranibizumab.
"Results from the phase 2 study have shown that VEGF Trap-Eye has the potential to significantly reduce retinal thickness and improve vision," said Kemal Malik, MD, head of global development and member of the Bayer HealthCare Executive Committee. "Dosing of the first patient in this confirmatory phase 3 trial is an important milestone for this compound intended to treat a devastating ocular disease that impacts millions of people worldwide."
"New therapies are still needed to provide optimal care to patients with wet AMD," said George D. Yancopoulos, MD, PhD, president of Regeneron Research Laboratories. "This global phase 3 clinical program will provide additional data to further evaluate the efficacy and safety of VEGF Trap-Eye using different dosing regimens."
Bayer HealthCare and Regeneron are collaborating on the global development of VEGF Trap-Eye for treatment of wet AMD, diabetic eye diseases, and other ocular diseases and disorders. Once approved, Bayer will market VEGF Trap-Eye outside the United States, where both 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. In the first year, the VIEW 2 study will evaluate the safety and efficacy of VEGF Trap-Eye at doses of 0.5 mg and 2 mg administered at 4-week intervals and 2 mg at an 8-week dosing interval, including 1 additional 2 mg dose at week 4. Patients randomized to the ranibizumab arm of the trial will receive an 0.5-mg dose every 4 weeks. After the first year of treatment, patients will continue to be followed and treated for another year on a flexible, criteria-based extended regimen with a dose administered at least every 12 weeks, but not more often than every 4 weeks until the end of the study.
The primary endpoint of the study is the proportion of patients treated with VEGF Trap-Eye who maintain vision at the end of 1 year, compared to patients receiving ranibizumab. Maintenance of vision is defined as losing fewer than 3 lines (equivalent to 15 letters) on the ETDRS chart. Key secondary endpoints include the mean change from baseline in visual acuity as measured by ETDRS and the proportion of patients who gained at least 15 letters of vision at week 52. VIEW 2 primary analysis results are expected in 2011.
|■Sub-tenon's delivery of bevacizumab. In a rabbit study conducted by researchers at the University of Missouri and presented at the 2008 ARVO meeting, researchers injected 1.25 mg of bevacizumab intravitreally and 12.5 mg of bevacizumab in the sub-tenon's space.|
Average vitreous bevacizumab concentrations (microgram/mL) following intravitreal injection was measured at 114.1 at 6 hours and 158.9 at 24 hours. Average concentration following sub-tenon's injection was 3.1 at 6 hours and 11.8 at 96 hours.
The researchers concluded that some bevacizumab reached measurable levels in the vitreous, though far less than the levels recorded by intravitreal injection. Whether the levels achieved through sub-tenon's injection are adequate to inhibit neovascular membranes is unknown.
■ Ranibizumab study for DME. Six-month data from the READ-2 study, conducted by Johns Hopkins University, shows that ranibizumab alone produced far greater improvement in visual acuity and foveal thickness than laser therapy or laser therapy plus ranibizumab in patients with diabetic macular edema (DME).
READ-2 is a phase 2, randomized, multicenter clinical trial evaluating the safety and efficacy of 0.5 mg ranibizumab monotherapy compared to laser photocoagulation alone and ranibizumab in combination with laser in 126 patients with DME.
The study is investigator-sponsored and supported by the Juvenile Diabetes Research Foundation and Genentech Inc.
■ Verteporfin/Ranibizumab study. QLT Inc., the developer of verteporfin photodynamic therapy for wet AMD, has completed enrolling 160 patients in the company's phase 2 RADICAL trial to determine if combination therapy with verteporfin reduces retreatment rates compared with an anti-VEGF antibody, while also maintaining similar vision outcomes and an acceptable safety profile.
"The completion of enrollment in the RADICAL trial signifies that we are 1 step closer to our goal of having the use of Visudyne followed by Lucentis, with or without an antiinflammatory agent, potentially added to the product's label," said Bob Butchofsky, QLT president and CEO.
The RADICAL trial is a phase 2, multicenter, randomized, single-masked study comparing reduced-fluence verteporfin/ranibizumab combination therapies and ranibizumab monotherapy. Patients are randomized to receive 1 of 4 treatments: reduced-fluence verteporfin followed by ranibizumab; reduced-fluence verteporfin followed by ranibizumab-dexamethasone triple therapy: very low-fluence verteporfin followed by ranibizumab-dexamethasone triple therapy; or ranibizumab monotherapy. The trial will span 24 months.
■ Ranibizumab/Medidur study. Alimera Sciences Inc., a privately held ophthalmic drug development company, said that enrollment has begun for a pilot study to assess the safety and efficacy of its Medidur FA (fluocinolone acetonide) insert in conjunction with ranibizumab in patients with the wet form of AMD.
The study, which will be performed under an investigator-sponsored IND, will compare 2 doses of Medidur FA (0.2 and 0.5 mg/day) in patients who have been treated with ranibizumab for at least 6 months. The change from baseline in parameters such as visual acuity and retinal thickness will be assessed, in addition to comparing the number of ranibizumab injections post-randomization vs pre-randomization
"Alimera Sciences is pleased to support this study design because it will provide preliminary information on the potential of Medidur FA to maintain the efficacy established with ranibizumab while reducing the number of ranibizumab treatments," said Ken Green, PhD, senior vice president and chief scientific officer for Alimera Sciences. RP
Radiation Therapy for Wet AMD
NeoVista Has Promising 1-Year Data.
■ NeoVista Inc. recently released promising results from a 1-year feasibility study of the company's novel epiretinal brachytherapy for the wet form of AMD. The data from the study, which was initiated by NeoVista to test the efficacy and safety of its therapy when used in conjunction with bevacizumab, showed a marked improvement in mean visual acuity (VA).
In the ongoing nonrandomized, multicenter feasibility study, 34 subjects (mean age, 72 years) with predominantly classic, minimally classic, or occult (with no classic) choroidal neovascularization (CNV) received a single 24-Gy treatment of NeoVista's epiretinal brachytherapy in combination with 2 injections of bevacizumab, 1 dose prior to or at the time of radiation delivery and another 1 month later, depending on the arm of the trial in which the patient was enrolled.
After 12 months of follow-up on 33 trial participants, researchers found that subjects had experienced a mean improvement in VA of 10 letters using the ETDRS test; 94% of patients lost fewer than 15 letters, 39% gained 15 or more letters, and 12% gained 30 or more letters. Seventy-six percent of the patients in the study did not require additional injections of bevacizumab throughout the year.
Most adverse events were related to the vitrectomy procedure (retinal tear, retinal detachment, subretinal hemorrhage, and vitreous hemorrhage). No events related to radiation toxicity have been reported to date.
Jeffrey S. Heier, MD, a retinal specialist, partner at Ophthalmic Consultants of Boston, and a consultant for NeoVista, presented the 1-year data obtained from trial participants who enrolled from June 2006 to April 2007 at 2 centers in Brazil and 1 in Mexico.
"As more data are collected and analyzed surrounding this 1-time surgical procedure, we're continuing to see the potential of the concomitant approach to treating wet AMD," said Dr. Heier. "Unlike previous attempts with radiation therapy, NeoVista has developed a means of delivering targeted beta radiation to choroidal neovascular membranes with minimal penetration, resulting in little effect on the surrounding healthy tissue."
In contrast to other forms of radiation therapy for wet AMD, NeoVista's approach delivers the peak dose of energy directly to the lesion without irreparably damaging the normal retinal vasculature.
Utilizing strontium 90, the focused energy is delivered to a target area up to 3 mm in depth and up to 5.4 mm in diameter. According to the company, the systemic exposure to radiation is minimal, as the effective dose to the entire body from NeoVista's epiretinal device is less than that from a typical chest x-ray.
"We've seen a significant amount of promise so far with epiretinal brachytherapy, and we're excited to see the ultimate potential of the therapy when evaluated in our definitive phase 3 CABERNET trial," said John N. Hendrick, president and CEO of NeoVista.
The CABERNET (CNV Secondary to AMD Treated with BEta RadiatioN Epiretinal Therapy) trial is a multicenter, randomized, controlled phase 3 study that will enroll 450 subjects at 30 clinical centers in the United States and other centers worldwide. The study will evaluate the safety and efficacy of NeoVista's epiretinal beta radiation therapy delivered concomitantly with the FDA-approved antiangiogenic therapy ranibizumab, vs ranibizumab alone.
AAO Joins IHS in DR Initiative
Effort Targets Native Americans.
■ The American Academy of Ophthalmology and the Indian Health Service (IHS), an agency of the US Department of Health and Human Services, have established a pilot program to provide evaluation and surgical treatment for diabetic retinopathy within high-risk American Indian and Alaska Native populations that have limited access to these services.
American Indians and Alaska Natives have almost 3 times the mortality rate for diabetes as the general US population. However, less than 50% of American Indians and Alaska Natives with diabetes receive an annual diabetic eye examination.
"This partnership is an important link to address an unmet need, providing evaluation and possible treatment of vision-threatening diabetic retinopathy regardless of the ability to pay," said H. Dunbar Hoskins Jr., MD, executive vice president of the Academy.
The program will be administered in association with the Minnesota Academy of Ophthalmology and the North Dakota Society of Eye Physicians and Surgeons for patients identified and referred by the pilot facilities in Cass Lake and Red Lake, MN. It will increase access to quality care by volunteer ophthalmologists, independent of a patient's or referring facility's capacity to pay for the services. It is limited to appropriate treatments such as laser applications and intraocular injections in the doctors' private offices. Volunteer physicians will complete an orientation that includes topics specific to American Indian and Alaska Native cultures, practices, and beliefs.
"We are extremely grateful to the Academy for working with the IHS to provide this critical and much needed treatment," said IHS Director Robert G. McSwain. "I know that our patients will be grateful for this generous assistance from the Academy and volunteer members."