Active Substance: aflibercept
Common Name: aflibercept
ATC Code: S01LA05
Marketing Authorisation Holder: Bayer Pharma AG
Active Substance: aflibercept
Authorisation Date: 2012-11-22
Therapeutic Area: Wet Macular Degeneration
Pharmacotherapeutic Group: Ophthalmologicals
Eylea is indicated for adults for the treatment of:
- neovascular (wet) age-related macular degeneration (AMD);
- visual impairment due to macular oedema secondary to central-retinal-vein occlusion (CRVO).
What is Eylea?
Eylea is a solution for injection into the eye that contains the active substance aflibercept. It is available as a prefilled syringe or as a vial.
What is Eylea used for?
Eylea is used to treat adults with:
- the ‘wet’ form of age-related macular degeneration (AMD), a disease that affects the central part of the retina (called the macula) at the back of the eye. The wet form of AMD is caused by the abnormal growth of blood vessels under the macula, which may leak fluid and blood and cause swelling;
- macular oedema (swelling of the macula) that follows blockage of the main vein carrying blood from the retina, a condition known as central-retinal-vein occlusion (CRVO).
The macula provides central vision that is needed to see detail for everyday tasks such as driving, reading and recognising faces. The diseases cause the gradual loss of the central part of a person’s vision.
The medicine can only be obtained with a prescription.
How is Eylea used?
Eylea must be given as an intravitreal injection (injection into the vitreous humour, the jelly-like fluid in the eye) by a qualified doctor who is experienced in giving intravitreal injections.
For wet AMD, one injection of 2 mg is given into the affected eye every month for three consecutive months, followed by one injection every two months. After one year of treatment, injections may be given less frequently depending on the response to treatment.
For macular oedema following CRVO, one injection of 2 mg is given into the affected eye every month as long as the condition responds with further improvement. Patients’ vision should be monitored at each injection, and treatment should not be continued if there is no response within three months of starting. In those patients who do respond, consideration may be given to stopping treatment, or giving it less frequently, once the condition has been stable for three months.
The procedure should be carried out under sterile conditions. The syringe and the vial are for single use only. The prefilled syringe contains more than the recommended dose, therefore when preparing the injection, the doctor must expel the excess volume and ensure the injection of the correct dose. After the injection, the pressure within the eye should be checked.
How does Eylea work?
Aflibercept is an engineered protein that has been designed to attach to and block the effects of a substance called vascular endothelial growth factor A (VEGF-A). It can also attach to other proteins such as placental growth factor (PlGF). VEGF-A and PlGF are involved in stimulating the abnormal growth of blood vessels in patients with AMD. By blocking these factors, aflibercept reduces the growth of the blood vessels and controls the leakage and swelling.
Aflibercept is produced by a method known as ‘recombinant DNA technology’: it is made by cells into which a gene (DNA) has been introduced that makes them able to produce aflibercept.
How has Eylea been studied?
Eylea was investigated in two main studies involving a total of around 2,400 patients with the wet form of AMD. The studies compared Eylea (given either as 0.5 mg every four weeks, 2 mg every four weeks or 2 mg every eight weeks, all after three initial monthly doses) with ranibizumab, another treatment for AMD, which is given by injection into the eye every four weeks. The main measure of effectiveness was the proportion of patients who maintained vision (defined as losing less than 15 letters in a standard eye test) after the first year of treatment.
Both studies also looked at the maintenance of the effect in the second year of treatment, during which the number of injections and the time between injections were adjusted depending on the vision and changes within the eye.
Eylea was also investigated in two other main studies involving 366 patients with macular oedema following CRVO. These compared a monthly injection of Eylea 2 mg every four weeks with a sham injection using a syringe without a needle. The main measure of effectiveness was the proportion of patients whose vision improved by 15 or more letters on an eye test after 24 weeks of treatment. The studies also looked at the effects of treatment on an as-needed basis after 24 weeks.
What benefit has Eylea shown during the studies?
Eylea was shown to be as effective as ranibizumab in maintaining vision in patients with wet AMD: looking at the results of the two studies together, the proportions of patients who maintained vision were 96.1% (517 out of 538), 95.4% (533 out of 559) and 95.3% (510 out of 535) for 0.5 mg Eylea every four weeks, 2 mg Eylea every four weeks and 2 mg Eylea every eight weeks, respectively, compared with 94.4% (508 out of 538) of patients treated with ranibizumab every four weeks.
During the second year of treatment, the effectiveness was generally maintained, with a majority of patients receiving injections at an extended dosing interval of 10 weeks, although a small number of patients occasionally needed more frequent injections (such as monthly).
Eylea also produced a significant improvement in vision in patients with macular oedema following CRVO. Overall about 60% of those given Eylea had an improvement of 15 letters or more in the eye test at week 24, compared with 17% of those given sham injections. The benefit was largely maintained with as-needed treatment up to 52 weeks, although some of the benefit seemed to be lost when patients were treated and followed up for longer periods than this.
What is the risk associated with Eylea?
The most common side effects (affecting at least 1 in 20 patients) reported with Eylea in patients with wet AMD and macular oedema resulting from CRVO are conjunctival haemorrhage (bleeding at the front of the eye), eye pain, vitreous detachment (detachment of the jelly-like substance inside the eye), cataract (clouding of the lens), vitreous floaters (small particles or spots in the vision) and increased intraocular pressure (increased pressure inside the eye). In those with macular oedema resulting from CRVO, the most common side effects also include increased tear flow and ocular hyperaemia (bloodshot eyes). Serious side effects (seen in less than 1 in 1,000 patients) can occur after Eylea injection, including endophthalmitis (an infection inside the eye), traumatic cataract (clouding of the lens due to injury), temporarily increased intraocular pressure and vitreous detachment in macular oedema. For the full list of all side effects reported with Eylea, see the package leaflet.
Eylea must not be used in people who are hypersensitive (allergic) to aflibercept or any of the other ingredients. It must not be used in patients who have or are thought to have ocular or periocular infections (infections in or around the eyes), or in patients who have severe inflammation inside the eye.
Why has Eylea been approved?
The CHMP noted that for wet AMD, Eylea was as effective as ranibizumab in maintaining patients’ vision after the first year of treatment. In addition the CHMP considered that Eylea was beneficial in improving patients’ vision with macular oedema resulting from CRVO. The CHMP further noted that there were no major or unexpected safety concerns with Eylea. Therefore, the CHMP decided that Eylea’s benefits are greater than its risks and recommended that it be given marketing authorisation.
What measures are being taken to ensure the safe use of Eylea?
The company that makes Eylea will provide educational material for doctors (to minimise the risks associated with the injection in the eye) and for patients (so they can recognise any serious side effects, and know when to seek urgent attention from their doctor). In addition, the company will carry out studies on the longer term use of Eylea.
Other information about Eylea
The European Commission granted a marketing authorisation valid throughout the European Union for Eylea on 22 November 2012.
For more information about treatment with Eylea, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.
Source: European Medicines Agency
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