Top-line interim data from a Phase II trial showed that Regeneron Pharmaceuticals Inc.'s VEGF Trap-Eye product improved vision in patients with age-related macular degeneration, results that the company hopes to duplicate in a pivotal program expected to start later this year.
That news pushed the Tarrytown, N.Y.-based firm's stock (NASDAQ:REGN) up $2.85, or 14.9 percent, Tuesday to close at $22.
While Regeneron will wait to disclose detailed data at an upcoming scientific conference, the company reported that its VEGF Trap-Eye, a fully human, soluble VEGF fusion protein, met its primary endpoint, showing a statistically significant reduction in retinal thickness after 12 weeks compared with baseline. That data was based on the first 78 of a planned 150 patients who completed 12 weeks of study.
The company opted for retinal thickness as a "more precise" primary endpoint than visual acuity because it's measured by objective optical coherence tomography scans and is "not based on patient effort," Regeneron said. Visual acuity, however, was measured as a secondary endpoint and also showed statistically significant improvement. Patients from five dose groups showed an overall increase of 5.9 letters.
Regeneron has not yet disclosed a design for its Phase III VEGF Trap-Eye program, which is partnered with Leverkusen, Germany-based Bayer Healthcare AG. The trial is expected to begin in the second half of 2007, though the company also declined to speculate on a timeline for the study's completion and subsequent regulatory filing.
Designed to bind to vascular endothelial growth factor, VEGF Trap-Eye targets the same pathway as Lucentis (ranibizumab), the wet AMD drug marketed by South San Francisco-based Genentech Inc. Since its mid-2006 approval, Lucentis - along with Genentech's anti-VEGF cancer drug Avastin (bevacizumab) in off-label use - has garnered a large share of the wet AMD market. In the fourth quarter of 2006, Lucentis raked in sales of $217 million.
Genentech's product has hurt competitors, such as Macugen, from OSI Pharmaceutical Inc., and Visudyne photodynamic therapy, from QLT Inc. Since Lucentis' launch, Melville, N.Y.-based OSI decided to halt or limit ongoing research in eye diseases, and Vancouver, British Columbia-based QLT reported a 28 percent decrease in Visudyne sales for the fourth quarter.
Lucentis' success also has prompted some other companies to rethink spending money on their own wet AMD programs. Most recently, Genaera Corp., of Plymouth Meeting, Pa., opted to scrap its late-stage drug, Evizon (squalamine lactate), which was enrolling patients too slowly in a Phase III trial. (See BioWorld Today, Jan. 5, 2007.)
Regeneron executives have said that VEGF Trap-Eye might prove to bind to VEGF with greater affinity than Lucentis. The product is designed to bind to all forms of VEGF-A, plus the related placental growth factor.
The Phase II study randomized patients into five groups for intravitreal administration of VEGF Trap-Eye in one eye. Two groups received either 0.5 mg or 2 mg of VEGF Trap-Eye every four weeks, and three groups received a single dose of 0.5 mg, 2 mg, or 4 mg. Retinal thickness is determined through OCT scans, and visual acuity is defined as the total number of letters read correctly on the Early Diabetic Retinopathy Study chart. Data showed that all but one patient in the interim study group maintained or improved vision at 12 weeks, and while the visual acuity was numerically greater in patients receiving injections every four weeks, the difference was not statistically significant, which indicates that VEGF Trap-Eye could improve vision at a dosing frequency of less than every four weeks.
The most common adverse events typically were associated with the intravitreal injections, and no drug-related serious adverse events were reported.
Regeneron holds all rights to VEGF Trap-Eye in the U.S., and could receive up to $320 million from a joint commercialization deal signed last fall with Bayer for ex-U.S. sales. That agreement includes up to $110 million in milestones, with the next payment due at the start of Phase III. (See BioWorld Today, Oct. 20, 2006.)
Outside of ophthalmology, Regeneron is testing in VEGF Trap in cancer. That program is partnered with Paris-based Sanofi Aventis Group in a deal worth a potential $400 million in total milestones to Regeneron, plus a chance to share equally in worldwide profits, except for Japan. (See BioWorld Today, Dec. 23, 2005.)