CLINICAL TRIAL SPOTLIGHT

Trapping the Progress of AMD

Regeneron's VEGF Trap-Eye enters phase 3 trials.

ANDREW E. MATHIS, PhD, MEDICAL EDITOR

With so much attention paid over the last year to ranibizumab (Lucentis, Genentech) as a treatment for age-related macular degeneration (AMD), comparatively less attention has been paid to other interventions under investigation. One of these treatments now entering phase 3 trials is the vascular endothelial growth factor (VEGF) Trap-Eye, developed by Regeneron Pharmaceuticals, Inc. (Tarrytown, NY).

The Double-Masked Study of Efficacy and Safety of IVT VEGF Trap-Eye in Subjects With Wet AMD trial (called VIEW 1) began enrolling patients in August. Regeneron and its development sponsor Bayer HealthCare AG (Leverkusen, Germany) intend to enroll approximately 1200 patients in over 200 centers in the United States and Canada. Avner Ingerman, MD, vice president, clinical sciences, ophthalmology, and the study director, explained the mechanism of action of VEGF Trap-Eye to Retinal Physician.

"VEGF Trap-Eye is a novel fusion protein," Dr. Ingerman said, "composed of a fully humanized sequence of VEGF receptor sites. It 'traps' or binds VEGF with very high affinity, therefore having the potential for a more complete blockade, as well as a long-lasting effect. This more complete blockade may lead to a greater visual benefit for the patient, while the longer-lasting effect may be translated into a lower dosing frequency."

As the trial's name suggests, VEGF Trap-Eye is administered intravitreally. In the VIEW 1 trial, the 1200 patients will be randomized into 4 study arms: (1) Patients receiving 0.5 mg/month of VEGF Trap-Eye; (2) patients receiving 2 mg/month of VEGF Trap-Eye; (3) patients receiving 2 mg of VEGF Trap-Eye every 8 weeks; and (4) a ranibizumab group receiving monthly injections of 0.5 mg. The patients will be followed for 2 years — a Food and Drug Administration (FDA) requirement for phase 3 trials.

George D. Yancopoulos, MD, PhD, president of the research laboratories and chief scientific officer at Regeneron, explained the endpoints of the VIEW 1 study. "We're going after the same endpoints that ranibizumab was approved for," Dr. Yancopoulos said, "and we're going for noninferiority. The same study can both show noninferiority and also show benefits that would indicate superiority, eg, increased average letter gain and the number patients who gained 3 or more lines of vision on an Early Treatment of Diabetic Retinopathy Study chart."

Dr. Yancopoulos is cautiously optimistic that the result of this trial will be favorable in comparison to the data available regarding ranibizumab. Speaking of phase 1 and 2 data, some of which was presented at the Retina Society meeting at the end of last month, Dr. Yancopoulos said, "The noninferiority endpoint, which is the primary endpoint in the study, would be met if we prevented vision loss as well as ranibizumab. We will also look at the proportion of patients who improve their vision during the trial."

One important area where Dr. Yancopoulos hopes to make a significant impact will be the number of enrollees who not only have improvement in vision — an established outcome of monthly treatment with ranibizumab — but also those patients who are able to have their best-corrected visual acuity (BCVA) improve from 20/200 (ie, legal blindness). "If we are able to help these patients, they won't be able to drive," Dr. Yancopoulos said, "which requires 20/40 BCVA, but they'll be able to read again, even if it's using large-print books."

Finally, Dr. Yancopoulos pointed to earlier VEGF Trap-Eye data indicating that a single injection was enough to maintain vision improvement compared to baseline after 3 months, whereas with ranibizumab, vision deteriorated after initial improvement with a single injection. "Not only are we trying to give better ultimate vision," Dr. Yancopoulos said, "but we want to provide a more convenient dosing schedule. Our study will examine a dosing schedule in which patients would only have to get half the number of injections currently required."

The second phase 3 study, to be called VIEW 1, will be conducted by Bayer, according to Dr. Ingerman. RP