EYLEA SIDE EFFECTS
- Generic Name: aflibercept
- Brand Name: Eylea
- Drug Class: Macular Degeneration Agents, Ophthalmics, VEGF Inhibitors
SIDE EFFECTS
The following potentially serious adverse reactions are described elsewhere in the labeling:
- Hypersensitivity.
- Endophthalmitis and retinal detachments.
- Increase in intraocular pressure.
- Thromboembolic events.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in other clinical trials of the same or another drug and may not reflect the rates observed in practice.
A total of 2980 patients treated with EYLEA constituted the safety population in eight phase 3 studies. Among those, 2379 patients were treated with the recommended dose of 2 mg. Serious adverse reactions related to the injection procedure have occurred in <0.1% of intravitreal injections with EYLEA including endophthalmitis and retinal detachment. The most common adverse reactions (≥5%) reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and intraocular pressure increased.
Neovascular (Wet) Age-Related Macular Degeneration (AMD)
The data described below reflect exposure to EYLEA in 1824 patients with wet AMD, including 1223 patients treated with the 2-mg dose, in 2 double-masked, controlled clinical studies (VIEW1 and VIEW2) for 24 months (with active control in year 1).
Safety data observed in the EYLEA group in a 52-week, double-masked, Phase 2 study were consistent with these results.
Table 1: Most Common Adverse Reactions (≥1%) in Wet AMD Studies
| Adverse Reactions | Baseline to Week 52 | Baseline to Week 96 | ||
| EYLEA (N=1824) |
Active Control (ranibizumab) (N=595) |
EYLEA (N=1824) |
Control (ranibizumab) (N=595) |
|
| Conjunctival hemorrhage | 25% | 28% | 27% | 30% |
| Eye pain | 9% | 9% | 10% | 10% |
| Cataract | 7% | 7% | 13% | 10% |
| Vitreous detachment | 6% | 6% | 8% | 8% |
| Vitreous floaters | 6% | 7% | 8% | 10% |
| Intraocular pressure increased | 5% | 7% | 7% | 11% |
| Ocular hyperemia | 4% | 8% | 5% | 10% |
| Corneal epithelium defect | 4% | 5% | 5% | 6% |
| Detachment of the retinal pigment epithelium | 3% | 3% | 5% | 5% |
| Injection site pain | 3% | 3% | 3% | 4% |
| Foreign body sensation in eyes | 3% | 4% | 4% | 4% |
| Lacrimation increased | 3% | 1% | 4% | 2% |
| Vision blurred | 2% | 2% | 4% | 3% |
| Intraocular inflammation | 2% | 3% | 3% | 4% |
| Retinal pigment epithelium tear | 2% | 1% | 2% | 2% |
| Injection site hemorrhage | 1% | 2% | 2% | 2% |
| Eyelid edema | 1% | 2% | 2% | 3% |
| Corneal edema | 1% | 1% | 1% | 1% |
| Retinal detachment | <1% | <1% | 1% | 1% |
Less common serious adverse reactions reported in <1% of the patients treated with EYLEA were hypersensitivity, retinal tear, and endophthalmitis.
Macular Edema Following Retinal Vein Occlusion (RVO)
The data described below reflect 6 months exposure to EYLEA with a monthly 2 mg dose in 218 patients following central retinal vein occlusion (CRVO) in 2 clinical studies (COPERNICUS and GALILEO) and 91 patients following branch retinal vein occlusion (BRVO) in one clinical study (VIBRANT).
Table 2: Most Common Adverse Reactions (≥1%) in RVO Studies
| Adverse Reactions | CRVO | BRVO | ||
| EYLEA (N=218) |
Control (N=142) |
EYLEA (N=91) |
Control (N=92) |
|
| Eye pain | 13% | 5% | 4% | 5% |
| Conjunctival hemorrhage | 12% | 11% | 20% | 4% |
| Intraocular pressure increased | 8% | 6% | 2% | 0% |
| Corneal epithelium defect | 5% | 4% | 2% | 0% |
| Vitreous floaters | 5% | 1% | 1% | 0% |
| Ocular hyperemia | 5% | 3% | 2% | 2% |
| Foreign body sensation in eyes | 3% | 5% | 3% | 0% |
| Vitreous detachment | 3% | 4% | 2% | 0% |
| Lacrimation increased | 3% | 4% | 3% | 0% |
| Injection site pain | 3% | 1% | 1% | 0% |
| Vision blurred | 1% | <1% | 1% | 1% |
| Intraocular inflammation | 1% | 1% | 0% | 0% |
| Cataract | <1% | 1% | 5% | 0% |
| Eyelid edema | <1% | 1% | 1% | 0% |
Less common adverse reactions reported in <1% of the patients treated with EYLEA in the CRVO studies were corneal edema, retinal tear, hypersensitivity, and endophthalmitis.
Diabetic Macular Edema (DME) And Diabetic Retinopathy (DR)
The data described below reflect exposure to EYLEA in 578 patients with DME treated with the 2-mg dose in 2 double-masked, controlled clinical studies (VIVID and VISTA) from baseline to week 52 and from baseline to week 100.
Table 3: Most Common Adverse Reactions (≥1%) in DME Studies
| Adverse Reactions | Baseline to Week 52 | Baseline to Week 100 | ||
| EYLEA (N=578) |
Control (N=287) |
EYLEA (N=578) |
Control (N=287) |
|
| Conjunctival hemorrhage | 28% | 17% | 31% | 21% |
| Eye pain | 9% | 6% | 11% | 9% |
| Cataract | 8% | 9% | 19% | 17% |
| Vitreous floaters | 6% | 3% | 8% | 6% |
| Corneal epithelium defect | 5% | 3% | 7% | 5% |
| Intraocular pressure increased | 5% | 3% | 9% | 5% |
| Ocular hyperemia | 5% | 6% | 5% | 6% |
| Vitreous detachment | 3% | 3% | 8% | 6% |
| Foreign body sensation in eyes | 3% | 3% | 3% | 3% |
| Lacrimation increased | 3% | 2% | 4% | 2% |
| Vision blurred | 2% | 2% | 3% | 4% |
| Intraocular inflammation | 2% | <1% | 3% | 1% |
| Injection site pain | 2% | <1% | 2% | <1% |
| Eyelid edema | <1% | 1% | 2% | 1% |
Less common adverse reactions reported in <1% of the patients treated with EYLEA were hypersensitivity, retinal detachment, retinal tear, corneal edema, and injection site hemorrhage.
Safety data observed in 269 patients with nonproliferative diabetic retinopathy (NPDR) through week 52 in the PANORAMA trial were consistent with those seen in the phase 3 VIVID and VISTA trials (see Table 3 above).
Immunogenicity
As with all therapeutic proteins, there is a potential for an immune response in patients treated with EYLEA. The immunogenicity of EYLEA was evaluated in serum samples. The immunogenicity data reflect the percentage of patients whose test results were considered positive for antibodies to EYLEA in immunoassays. The detection of an immune response is highly dependent on the sensitivity and specificity of the assays used, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to EYLEA with the incidence of antibodies to other products may be misleading.
In the wet AMD, RVO, and DME studies, the pre-treatment incidence of immunoreactivity to EYLEA was approximately 1% to 3% across treatment groups. After dosing with EYLEA for 24-100 weeks, antibodies to EYLEA were detected in a similar percentage range of patients. There were no differences in efficacy or safety between patients with or without immunoreactivity.
SRC: NLM .