Date: 2012-02-20
Type of information:
phase: 3
Announcement: results
Company: Bayer Healthcare (Germany)Regeneron Pharmaceuticals (USA)
Product: VEGF Trap-Eye (aflibercept ophthalmic solution)
Action mechanism: VEGF Trap-Eye is a fully human, soluble VEGF receptor fusion protein that binds all forms of VEGF-A along with another vascular growth factor, the Placental Growth Factor (PlGF). VEGF Trap-Eye is a specific and highly potent blocker of VEGF-A and PlGF that has been demonstrated in preclinical models to bind these growth factors with greater affinity than their natural receptors.
Disease: macular edema due to central retinal vein occlusion (CRVO)
Therapeutic area: Ophtalmological diseases
Country:
Trial
details: The Phase 3 CRVO Program includes two studies: COPERNICUS (Controlled Phase 3 Evaluation of Repeated intravitreal administration of VEGF Trap-Eye In Central retinal vein occlusion: Utility and Safety) and the almost identical GALILEO (General Assessment Limiting Infiltration of Exudates in central retinal vein Occlusion with VEGF Trap-Eye). In both studies patients received six monthly injections of either VEGF Trap-Eye at a dose of 2mg or sham injections.
Patients in both trials were randomized in a 3:2 ratio with 114 patients receiving VEGF Trap-Eye and 74 randomized to the control arm in COPERNICUS and 104 patients randomized and treated with VEGF Trap-Eye and 68 randomized and treated in the control arm in GALILEO. At the end of the initial six months, all patients randomized to VEGF Trap-Eye were dosed on a PRN (as needed) basis for another six months. In the COPERNICUS trial, patients randomized to sham injections in the first six months were eligible to cross over to VEGF Trap-Eye PRN dosing in the second six months. During the second six months of the studies, all patients were eligible for rescue laser treatment. Visual acuity was measured as a score based on the total number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart, a standard chart used in research to measure visual acuity.
Latest
news: Bayer has announced that top-line results with VEGF Trap-Eye (aflibercept injection) after one year of treatment in the Phase 3 GALILEO study in patients with macular edema due to central retinal vein occlusion (CRVO) confirm the primary endpoint results that were seen after 24 weeks from the two pivotal trials, GALILEO and COPERNICUS. The results are also in line with previously reported one-year results from the COPERNICUS study. These data are being presented at the World Ophthalmology Congress in Abu Dhabi. The one-year GALILEO results showed that the proportion of subjects that gained at least 15 letters of vision from baseline to week 52 was 60.2% of patients receiving VEGF Trap-Eye, compared to 32.4% of patients receiving sham injections (exploratory tertiary endpoint; p=0.0004). In terms of gain in visual acuity from baseline until week 52, patients receiving VEGF Trap-Eye gained, on average, 16.9 letters of vision compared to a mean gain of 3.8 letters for patients receiving sham injections (exploratory tertiary endpoint; p<0.0001). The one-year COPERNICUS results showed that 55.3% of patients receiving VEGF Trap-Eye dosed monthly for 24 weeks, then on an as-needed (PRN) basis (guided by anatomic and visual acuity monitoring) over the next 28 weeks, gained at least 15 letters on an eye chart compared to 30.1% of patients who received sham injections for the first 24 weeks followed by VEGF Trap-Eye PRN from week 24 to week 52 (p=0.0006). Based on the results of these studies, Regeneron has already submitted a supplemental Biologics License Application (sBLA) in the U.S. and has been granted a FDA action date of September 23, 2012. Bayer HealthCare plans to file a marketing application with regulatory authorities in Europe in the second half of 2012.
The results achieved at week 52 corroborate the previously seen primary and secondary endpoints after 24 weeks, where 60.2 percent of patients receiving monthly VEGF Trap-Eye 2 milligrams (mg) gained at least 15 letters of vision from baseline, compared to 22.1 percent of patients receiving sham injections (primary endpoint; p<0.0001), and patients receiving VEGF Trap-Eye had a mean gain of 18 letters compared to a mean gain of 3.3 letters for patients with sham injections (secondary endpoint; p<0.0001).
Patients treated with VEGF Trap-Eye received an average of 2.5 VEGF Trap-Eye injections from week 24 to week 52. VEGF Trap-Eye was generally well tolerated. The most frequently reported ocular adverse events (> 10%) in the study eye in the VEGF Trap-Eye arm were eye pain, conjunctival hemorrhage, elevated intraocular pressure, macular edema, retinal hemorrhage, reduced visual acuity and retinal vascular disorder.
The most frequently reported adverse events in the sham group (>10%) were macular edema, retinal hemorrhage, retinal vascular disorder, eye irritation and reduction of visual acuity. 9.6% of patients in the VEGF Trap-Eye arm and 8.8% of patients in the sham arm presented with at least one ocular serious adverse event over the 52 weeks of the trial. The most frequently reported non-ocular adverse events (>5%) in the VEGF Trap-Eye arm were back pain, bronchitis, nasopharyngitis, headache, and hypertension. The most frequently reported non-ocular adverse events (>5%) in the sham group were fall, nasopharyngitis, headache, arthralgia, and hypertension.
Patients who went from monthly VEGF Trap-Eye dosing to PRN VEGF Trap-Eye dosing received a mean of 2.7 VEGF Trap-Eye injections, while patients who switched from sham to VEGF Trap-Eye PRN at week 24 received a mean of 3.9 VEGF Trap-Eye injections over 28 weeks. In terms of gain in visual acuity from baseline to week 52, patients receiving VEGF Trap-Eye gained, on average, 16.2 letters of vision compared to a mean gain of 3.8 letters for patients who switched from sham to VEGF Trap-Eye PRN (p<0.0001). At week 24, patients receiving VEGF Trap-Eye had a mean gain of 17.3 letters, while patients receiving sham had a mean loss of 4.0 letters (p<0.0001).
VEGF Trap-Eye was generally well tolerated. The most frequently reported ocular adverse events (> 10%) in the study eye in the VEGF Trap-Eye arm were conjunctival hemorrhage, eye pain, maculopathy, elevated intraocular pressure, reduced visual acuity, and vascular disorder of the optic disc. The most frequently reported adverse events in the sham to VEGF Trap-Eye PRN arm (>10%) were reduced visual acuity, conjunctival hemorrhage, retinal hemorrhage, vitreous hemorrhage, and elevated intraocular pressure. At week 52, 5.3% of patients receiving VEGF Trap-Eye (monthly to PRN) and 16.2% of patients (sham to VEGF Trap-Eye PRN) reported at least one ocular serious adverse event. The most frequently reported non-ocular adverse events (>5%) in the VEGF Trap-Eye arm were nasopharyngitis, sinusitis, bronchitis, influenza, and hypertension. The most frequently reported non-ocular adverse events (>5%) in the sham to VEGF Trap-Eye PRN arm were nasopharyngitis, present protein in urine, increased urine protein/creatinine ratio, increased blood glucose, and hypertension.
