Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that results from the National Institutes of Health (NIH)-sponsored, Diabetic Retinopathy Clinical Research Network comparative effectiveness study in patients with Diabetic Macular Edema (Protocol T) were published in the New England Journal of Medicine and a corresponding slide set was posted online at DRCR.net. EYLEA® (aflibercept) Injection demonstrated significantly greater improvement on the primary endpoint of mean visual acuity letter score change at one year [EYLEA +13 letters; bevacizumab (Avastin®) +10; ranibizumab (Lucentis®) +11]. These differences were driven by patients with moderate or worse vision loss at the start of the trial (worse than 20/40); in these patients, EYLEA showed a statistically significant 7-letter (approximately 1.5 lines on an eye chart) improvement over bevacizumab and a 5-letter (1 line on an eye chart) improvement over ranibizumab (EYLEA +19 letters; bevacizumab +12; ranibizumab +14).
"In this independent, government-sponsored diabetic macular edema study, EYLEA provided significantly greater efficacy, despite one fewer injection and fewer laser treatments than comparators," said George D. Yancopoulos, M.D., Ph.D., Chief Scientific Officer of Regeneron and President of Regeneron Laboratories. "The improvements with EYLEA relative to alternative anti-VEGF therapies were particularly apparent in the group with moderate or worse vision loss at the start of the trial, where there was a greater opportunity to demonstrate gains in vision."
Key efficacy results at 52 weeks included:
- In the overall population (n=660), for the primary endpoint of mean change from baseline in best corrected visual acuity (BCVA), patients receiving EYLEA had a mean change from baseline of +13 letters. Patients treated with bevacizumab had a mean change from baseline of +10 letters (p less than 0.001, EYLEA vs. bevacizumab) and patients treated with ranibizumab had a mean change from baseline of +11 letters (p=0.03, EYLEA vs. ranibizumab).
- In the pre-specified group of approximately 50 percent of patients (n=305) with baseline visual acuity worse than 20/40, patients receiving EYLEA had a mean change from baseline in BCVA of +19 letters (almost 4 lines). Patients treated with bevacizumab had a mean change from baseline of +12 letters (almost 2.5 lines) (p less than 0.001, EYLEA vs. bevacizumab) and patients treated with ranibizumab had a mean change from baseline of +14 letters (almost 3 lines) (p equals 0.003, EYLEA vs. ranibizumab). There were no differences in visual acuity changes in those patients with baseline vision of 20/40 or better, with all groups gaining approximately 8 letters. However, even in these patients, both EYLEA and ranibizumab showed a statistically significant improvement in retinal edema, as measured by Optical Coherence Tomography (OCT) compared to bevacizumab (p less than 0.001).
- In the overall population, 42 percent of patients receiving EYLEA gained at least 15 letters (3 lines on an eye chart) in BCVA from baseline compared to 29 percent of patients treated with bevacizumab (p=0.03) and 32 percent of patients treated with ranibizumab (p=0.07).
- In the patients with baseline visual acuity worse than 20/40, 67 percent of patients receiving EYLEA gained at least 15 letters in BCVA from baseline, compared to 41 percent of patients treated with bevacizumab (p less than 0.001) and 50 percent of patients treated with ranibizumab (p=0.01). In patients with baseline visual acuity of 20/40 or better, there were no significant differences among groups.
- The median number of injections using the protocol-specified retreatment regimen was one fewer in patients treated with EYLEA (9 injections) compared to bevacizumab (10 injections) and ranibizumab (10 injections).
- Macular laser treatments could be initiated at or after the 24-week visit and repeated as often as every 13 weeks based on protocol specified criteria. Macular laser treatment was performed at least once in 36 percent of the patients in the EYLEA group, 56 percent of patients in the bevacizumab group (p less than 0.001; EYLEA vs. bevacizumab) and 46 percent of patients in the ranibizumab group (p = 0.058 EYLEA vs. ranibizumab).
In this study, the rates of most ocular and systemic adverse events (AEs) were similar across the three study groups. Additional safety findings included:
- The rates of arterial thromboembolic events as defined by the Anti-Platelet Trialists' Collaboration (non-fatal stroke, non-fatal myocardial infarction, and vascular death) in the trial were 3 percent in the EYLEA group, 4 percent in the bevacizumab group and 5 percent in the ranibizumab group.
- There were no differences in intraocular inflammation among the three treatment groups.
- There were no significant differences in overall rates of major cardiovascular events among the groups. In a post hoc analysis of combined cardiac and vascular events, there were more events in the ranibizumab group (17 percent), compared to the EYLEA group (8 percent) and the bevacizumab group (9 percent) (nominal p equals 0.012); this included more cardiac events (11 percent ranibizumab; 6 percent EYLEA; 6 percent bevacizumab) and cerebrovascular events (5 percent ranibizumab; 0 percent EYLEA; 2 percent bevacizumab).
- The rate of death was 1 percent in the EYLEA group, 2 percent in the bevacizumab group, and 2 percent in the ranibizumab group.
The investigators plan to present the results at the Annual Macula Society Meeting, February 25-28, 2015 in Scottsdale, Arizona.
The independent, government-sponsored study was designed to compare three different anti-VEGF therapies, EYLEA, bevacizumab and ranibizumab, for the treatment of diabetic macular edema (DME). In the study, 660 patients were randomized to receive either EYLEA 2 milligrams (mg), bevacizumab 1.25 mg, or ranibizumab 0.3 mg dosed according to a protocol-specified algorithm. Patients were treated with focal/grid laser at or after the 24 week visit if: 1) the OCT central subfield thickness was greater than or equal to 250 microns or there was edema that was threatening the fovea and 2) the eye did not improve on OCT or visual acuity from the last two consecutive injections.