Regeneron Pharmaceuticals, Inc., a fully integrated biopharmaceutical company that discovers, invents, develops, manufactures, and commercializes medicines for the treatment of serious medical conditions, and Bayer HealthCare said that in an integrated analysis of two parallel phase III studies (VIEW 1 and VIEW 2) in patients with the neovascular form of age-related macular degeneration (wet AMD), patients treated with Eylea (aflibercept) injection. For intravitreal injection showed a sustained improvement in visual acuity at 96 weeks versus baseline. The 52-week results (primary analyses) from these studies have previously been reported.
During the first year of the VIEW 1 and VIEW 2 studies, patients were treated with three different dosing regimens of Eylea, 0.5 milligram (mg) every four weeks, 2mg every four weeks, and 2mg every eight weeks (following three initial monthly injections), compared to ranibizumab 0.5mg every four weeks. The Eylea 2mg every eight week regimen was recently approved by the US FDA, based on efficacy (maintenance of vision) that was clinically equivalent at one year to the monthly ranibizumab regimen. In the second year of the studies, patients were treated with the same dose per injection as in the first year and were evaluated monthly to determine need for retreatment. Patients were treated at least every 12 weeks. All year two analyses were considered exploratory.
In an integrated analysis of the VIEW 1 and VIEW 2 studies, the visual acuity gain from baseline in the Eylea 2mg every eight week group at week 96 was 7.6 letters compared to 8.4 letters at week 52, with an average of 11.2 injections over two years and 4.2 injections during the second year. The visual acuity gain from baseline in the monthly ranibizumab group at week 96 was 7.9 letters compared to 8.7 letters at week 52, with an average of 16.5 injections over two years and 4.7 injections during the second year. The results of each of the VIEW 1 and VIEW 2 studies were consistent with the integrated analysis.
The overall fewer average number of injections in the second year in the Eylea 2mg every eight week group compared to the ranibizumab group (4.2 versus 4.7) was driven by the fact that fewer patients needed more intense therapy in the Eylea group and those patients required fewer injections.
The proportion of patients who required frequent injections (six or more) during the second year was lower in the Eylea 2mg every eight week group compared to the ranibizumab group (15.9% versus 26.5%). In the 25% of patients who required the most intense therapy (the greatest number of injections), patients in the Eylea 2mg every eight week group required an average of 1.4 fewer injections in the second year compared to the ranibizumab group (6.6 versus 8.0). In the 25% of patients in each group who had the fewest number of injections in the second year, the average number of injections was similar (approximately 3 for both groups, corresponding to the protocol-mandated minimum number of injections).
A generally favourable safety profile was observed for both Eylea and ranibizumab. The incidence of ocular treatment emergent adverse events was balanced across all four treatment groups in both studies, with the most frequent events associated with the injection procedure, the underlying disease and/or the ageing process. The most frequent ocular adverse events (greater than 10% of patients for the overall study population) were conjunctival haemorrhage, eye pain, retinal haemorrhage, and visual acuity reduced. The most frequent serious non-ocular adverse events were typical of those reported in this elderly population who receive intravitreal treatment for wet AMD; the most frequently reported events (greater than 1% of patients for the overall study population) were falls, pneumonia, myocardial infarction and atrial fibrillation. There were no notable differences among the study arms. The incidence of arterial thrombotic events as defined by the “Anti-Platelet Trialists” group criteria was 3.2% of patients for ranibizumab and 3.3% of patients in the combined Eylea groups.
“These second year results confirm the sustainability of the vision gains achieved by Eylea with a less than monthly dosing frequency. Importantly, the second year data demonstrated that for patients that needed more anti-VEGF treatment, this was achieved with fewer injections using Eylea,” said George D Yancopoulos, chief scientific officer of Regeneron and president of Regeneron Laboratories. “As a reminder, the recommended dose for Eylea is 2mg every eight weeks following three initial monthly injections, which demonstrated visual acuity gains that were clinically equivalent to monthly ranibizumab. Retinal physicians and their wet AMD patients consider the predictable every eight week dosing regimen for Eylea as a significant advance that helps overcome the challenges of monthly office visits.”
Eylea (aflibercept) Injection, known in the scientific literature as VEGF Trap-Eye, is a recombinant fusion protein, consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 and formulated as an iso-osmotic solution for intravitreal administration. It acts as a soluble decoy receptor that binds VEGF-A and placental growth factor (PlGF) and thereby can inhibit the binding and activation of these cognate VEGF receptors.
In the US, Eylea is indicated for the treatment of patients with wet AMD.
Regeneron is collaborating with Bayer HealthCare on the global development of Eylea. Bayer submitted an application for marketing authorization in Europe for wet AMD in June 2011. Bayer HealthCare will market Eylea outside the United States, where the companies will share equally the profits from any future sales of Eylea. Regeneron maintains exclusive rights to Eylea in the US.