Eylea 114.3 mg/ml solution for injection

REC31184 (Var-91)

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1.      NAME OF THE MEDICINAL PRODUCT

Eylea 114.3 mg/ml solution for injection

Eylea 114.3 mg/ml solution for injection in pre‑filled syringe

2.      QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml solution for injection contains 114.3 mg aflibercept*.

Eylea 114.3 mg/ml solution for injection

Each vial contains 30.1 mg aflibercept in 0.263 ml solution. This provides a usable amount to deliver a single dose of 0.07 ml containing 8 mg aflibercept.

Eylea 114.3 mg/ml solution for injection in pre‑filled syringe

Each pre‑filled syringe contains 21 mg aflibercept in 0.184 ml solution. This provides a usable amount to deliver a single dose of 0.07 ml containing 8 mg aflibercept.

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4.2    Posology and method of administration

Eylea must only be administered by a qualified physician experienced in intravitreal injections.

Posology

The recommended dose is 8 mg aflibercept, equivalent to 0.07 ml solution. The posology is the same for the nAMD and DME indications. The 8 mg dose requires use of the Eylea 114.3 mg/mlvial.

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Method of administration

Each vial or pre‑filled syringe should only be used for the treatment of a single eye.

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6.4    Special precautions for storage

Eylea 114.3 mg/ml solution for injection

Store in a refrigerator (2 °C – 8 °C).

Do not freeze.

Keep the vial in the outer carton in order to protect from light.

Prior to usage, the unopened vial may be stored outside the refrigerator below 25 °C for up to 24 hours.

Eylea 114.3 mg/ml solution for injection in pre‑filled syringe

Store in a refrigerator (2 °C – 8 °C).

Do not freeze.

Keep the pre‑filled syringe in its blister and in the outer carton in order to protect from light.

Prior to usage, the unopened blister may be stored outside the refrigerator below 25 °C for up to 24 hours.

6.5    Nature and contents of container

Eylea 114.3 mg/ml solution for injection

Vial (type I glass) with a grey rubber stopper (chlorobutyl) sealed with an aluminium cap with white lid, and a 18 G, 5‑micron filter needle.

Each vial contains 0.263 ml solution.

Pack size of 1 vial and 1 filter needle.

Eylea 114.3 mg/ml solution for injection in pre‑filled syringe

Pre‑filled syringe (type I glass) with a grey plunger stopper (elastomeric rubber), a white Luer‑lock adaptor with a grey tip cap (elastomeric rubber) and a blue OcuClick dosing system (PC/ABS plastic).

Each pre‑filled syringe contains 0.184 ml solution.

Pack size of 1 pre‑filled syringe.

6.6    Special precautions for disposal and other handling

Eylea 114.3 mg/ml solution for injection

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Eylea 114.3 mg/ml solution for injection in pre‑filled syringe

The pre‑filled syringe with OcuClick dosing system is for single use in one eye only. Extraction of multiple doses from a single pre‑filled syringe with OcuClick dosing system may increase the risk of contamination and subsequent infection.

Do not use if the package or its components are expired, damaged, or have been tampered with.

Check the label on the pre‑filled syringe with OcuClick dosing system to make sure you have the strength of Eylea that you intended to use. The 8 mg dose requires use of the Eylea 114.3 mg/ml pre‑filled syringe.

The intravitreal injection should be performed with a 30 G × ½ inch injection needle (not included).

Use of a smaller size needle (higher gauge) than the recommended 30 G × ½ inch injection needle may result in increased injection forces.

Pre‑filled syringe with integrated OcuClick dosing system description

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8.      MARKETING AUTHORISATION NUMBER(S)

EU/1/12/797/003 - Eylea 114.3 mg/ml solution for injection

EU/1/12/797/004 - Eylea 114.3 mg/ml solution for injection in pre‑filled syringe

10.    DATE OF REVISION OF THE TEXT 

August 2024

REC31547, 32268, 32306, 32265, 32267, 32269 (Var-90)

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4.8    Undesirable effects

Summary of the safety profile

Serious adverse reactions were cataract (8.2% 4.0%), retinal haemorrhage (3.6% 2.6%), intraocular pressure increased (2.8% 2.4%), vitreous haemorrhage (1.2% 1.0%), cataract subcapsular (0.9% 0.5%), cataract nuclear (0.6%), retinal detachment (0.6% 0.4%), and retinal tear (0.5% 0.3%).

The most frequently observed adverse reactions in patients treated with Eylea 114.3 mg/ml were cataract (8.2% 4.0%), visual acuity reduced (4.4%), vitreous floaters (4.0% 3.5%), visual acuity reduced (3.2%), conjunctival haemorrhage (3.8% 3.1%), vitreous detachment (3.7% 2.9%), retinal haemorrhage (3.6% 2.6%), intraocular pressure increased (2.8% 2.4%), and eye pain (2.0%).

Table 1: All treatment‑emergent adverse reactions reported in patients with nAMD or DME treated with Eylea 114.3 mg/ml in phase II/III studies

System organ class                 Common                     Uncommon                     Rare

Immune system disorders        Hypersensitivity*         Hypersensitivity*

Eye disorders                           Corneal abrasion                                                    Blindness,

                                                                                        Uveitis                              Uveitis

                                                                                        Corneal abrasion

                                                                                        Eyelid oedema,                Eyelid oedema,

                                                                                        Ocular hyperaemia,

                                                                                        Injection site irritation     Injection site irritation,

                                                                                                                                 Lenticular opacities,

                                                                                                                                 Retinal degeneration,

                                                                                                                                 Eyelid irritation

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The following adverse reactions of Eylea 40 mg/ml are also considered expected with Eylea 114.3 mg/ml but have not been reported in the clinical studies with Eylea 114.3 mg/ml: ocular hyperaemia, retinal degeneration, abnormal sensation in eye, lenticular opacities, corneal epithelium defect, anterior chamber flare, eyelid irritation, endophthalmitis, blindness, traumatic cataract, hypopyon, severe anaphylactic/anaphylactoid reactions.

5.1    Pharmacodynamic properties

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Pharmacodynamic effects

nAMD

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The pharmacodynamic effects of aflibercept 114.3 mg/ml administered every 12 (8Q12) and every 16 (8Q16) weeks are described in comparison with aflibercept 40 mg/ml administered every 8 weeks (2Q8) for the nAMD indication. These effects are shown as the change in CNV size from baseline to week 12; change in total lesion area from baseline to weeks 48, 60, and 96; and change from baseline in central retinal thickness (CRT).

Table 2: Pharmacodynamic parameter (full analysis set) in the PULSAR study [updated]

Figure 1: LS mean change in central retinal thickness (CRT) from baseline through week 96 (full analysis set) in the PULSAR study [updated]

DME

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The pharmacodynamic effects of aflibercept 114.3 mg/ml administered every 12 (8Q12) and every 16 (8Q16) weeks are described in comparison with aflibercept 40 mg/ml administered every 8 weeks (2Q8) for the DME indication. These effects are shown as the change in the leakage area from baseline to weeks 48, 60, and 96.

Table 3: Pharmacodynamic parameter (full analysis set) in the PHOTON study [updated]

Figure 2: LS mean change in central retinal thickness (CRT) from baseline through week 96 (full analysis set) in the PHOTON study [updated]

Immunogenicity

After dosing with Eylea 114.3 mg/ml for up to 96 48 weeks treatment‑emergent antibodies to Eylea 114.3 mg/ml were detected in 2.5% 1.2% to 4.4% 3.8% of patients treated for DME and nAMD.

Clinical efficacy and safety

nAMD

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Results

At week 60, 43.1% of patients in the 8Q12‑group were extended to a treatment dosing interval of 16 weeks, and 38.5% of patients in the 8Q16‑group were extended to a treatment dosing interval of 20 weeks.

Patients in the 8Q12‑, 8Q16‑ and 2Q8‑groups who completed week 96 received a median (mean) of 9.0 (9.7), 8.0 (8.2) and 13.0 (12.8) injections, respectively.

At week 96, in the pooled 8Q12‑ and 8Q16‑groups 71.0% of patients had attained treatment intervals of ≥16 weeks, 46.8% of patients had attained treatment intervals of ≥20 weeks, and 27.8% of patients had attained treatment intervals of 24 weeks, while maintaining visual and anatomic outcomes.

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The treatment effect with Eylea 114.3 mg/ml in mean change in BCVA was maintained through week 96.

Table 4: Efficacy outcomes from the PULSAR study [updated]

Figure 3: LS mean change in BCVA as measured by ETDRS letter score from baseline through week 96 (full analysis set) in the PULSAR study [updated]

Figure 4: Last intended treatment interval at week 96

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No clinically meaningful differences were found between the 8Q12‑, 8Q16‑ and 2Q8‑groups in changes of NEI VFQ‑25 total score at week 48 and week 96 from baseline.

Efficacy results in evaluable subgroups for age, gender, geographic region, ethnicity, race, baseline BCVA, and lesion type were consistent with the results in the overall population.

Efficacy was generally maintained through week 96 60.

DME

Results

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At week 60, 42.6% of patients in the 8Q12‑group were extended to a treatment dosing interval of 16 weeks, and 34.2% of patients in the 8Q16‑group were extended to a treatment dosing interval of 20 weeks.

Patients in the 8Q12‑, 8Q16‑ and 2Q8‑groups who completed week 96 received a median (mean) of 9.0 (9.5), 8.0 (7.8) and 14.0 (13.8) injections, respectively.

At week 96, in the pooled 8Q12‑ and 8Q16‑groups 72.4% of patients had attained treatment intervals of ≥16 weeks, 44.3% of patients had attained treatment intervals of ≥20 weeks, and 26.8% of patients had attained treatment intervals of 24 weeks, while maintaining visual and anatomic outcomes.

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The treatment effect with Eylea 114.3 mg/ml in mean change in BCVA was maintained through week 96.

Table 5: Efficacy outcomes from the PHOTON study [updated]

Figure 5: LS mean change in BCVA as measured by ETDRS letter score from baseline through week 96 60 (full analysis set) in the PHOTON study [updated]

Figure 6: Last intended treatment interval at week 96

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No clinically meaningful differences were found between the 8Q12‑, 8Q16‑ and 2Q8‑groups in changes of NEI VFQ‑25 total score at week 48 and week 96 from baseline.

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Efficacy results in evaluable subgroups for age, gender, geographic region, ethnicity, race, baseline BCVA and baseline CRT and prior DME treatment were consistent with the results in the overall population.

Efficacy was generally maintained through week 96 60.

6.6    Special precautions for disposal and other handling

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Use of a smaller size needle (higher gauge) than the recommended 30 G × ½ inch injection needle may result in increased injection forces.

10 Date of revision of the text

May 2024

REC31547, 32268, 32306, 32265, 32267, 32269 (Var-90)

Note:

Text in blue = added text

Text in red with strikethrough = deleted text

Text in green = repositioned text

2.      What you need to know before you receive Eylea

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Pregnancy and breast‑feeding

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-                There is no limited experience on the use of Eylea in pregnant women. Women should not receive Eylea during pregnancy unless the potential benefit to the woman outweighs the potential risk to the unborn child.

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4.      Possible side effects

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-                uncommon side effect, which may affect up to 1 in 100 people

-  certain forms of clouding of the lens (cataract subcapsular/nuclear)

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Other possible side effects

Common (may affect up to 1 in 10 people):

-                allergic reactions

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-                damage to the clear layer of the eyeball in front of the iris (punctate keratitis, corneal abrasion)

Uncommon (may affect up to 1 in 100 people):

-                allergic reactions

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-                inflammation in the iris, of other parts of the eye, or the gel‑like substance inside the eye (uveitis, iritis, iridocyclitis, vitritis)

-                certain forms of clouding of the lens (cataract cortical/nuclear)

-                damage to the front layer of the eyeball (corneal abrasion/erosion)

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-                swelling of the eyelid

-                redness of the eye (ocular hyperaemia)

-                irritation at injection site

Rare (may affect up to 1 in 1 000 people):

-                blindness

-                inflammation of other parts of the eye (uveitis)

-                swelling of the eyelid

-                irritation at injection site

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-                clouding of the lens (lenticular opacities)

-                degeneration of the light sensitive membrane at the back of the eye (retinal degeneration)

-                eyelid irritation

Besides the above the following side effects may occur although they have not been reported in clinical studies:

-                redness of the eye (ocular hyperaemia)

-                degeneration of the light sensitive membrane at the back of the eye (retinal degeneration)

-                abnormal sensation in eye clouding of the lens (lenticular opacities), clouding of the lens due to injury (traumatic cataract)

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-                eyelid irritation

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-                blindness

-                clouding of the lens due to injury (traumatic cataract)

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6.      Contents of the pack and other information

This leaflet was last revised in 05/2024

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The following information is intended for healthcare professionals only:

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The intravitreal injection should be performed with a 30 G × ½ inch injection needle (not included).

Use of a smaller size needle (higher gauge) than the recommended 30 G × ½ inch injection needle may result in increased injection forces.

The unopened vial may be stored outside the refrigerator below 25 °C for up to 24 hours.

The unopened vial may be stored outside the refrigerator below 25 °C for up to 24 hours.

R:\Pharma\3. Bayer\Eylea\3. Artwork\PL - WORD VERSION\Draft\Vial_8mg\EMEA-H-C-002392-IB-0089 – Storage Condition 8mg

The unopened vial may be stored outside the refrigerator below 25 °C for up to 24 hours.