Vascular Endothelial Growth Factor Inhibitor

Eylea HD

Approved 18 Aug 2023InjectionInjectable

Indications

EYLEA HD is indicated for the treatment of: EYLEA HD is a vascular endothelial growth factor (VEGF) inhibitor indicated for the treatment of patients with: Neovascular (Wet) Age-Related Macular Degeneration (nAMD) ( 1.1 ) Diabetic Macular Edema (DME) ( 1.2 ) Diabetic Retinopathy (DR) ( 1.3 ) Macular Edema Following Retinal Vein Occlusion (RVO) ( 1.4 )

1.1 Neovascular (Wet) Age-Related Macular Degeneration (nAMD)

1.2 Diabetic Macular Edema (DME)

1.3 Diabetic Retinopathy (DR)

1.4 Macular Edema Following Retinal Vein Occlusion (RVO)

Contraindications

Ocular or periocular infection ( 4.1 ) Active intraocular inflammation ( 4.2 ) Hypersensitivity ( 4.3 )

4.1Ocular or Periocular Infections

EYLEA HD is contraindicated in patients with ocular or periocular infections.

4.2Active Intraocular Inflammation

EYLEA HD is contraindicated in patients with active intraocular inflammation.

4.3Hypersensitivity

EYLEA HD is contraindicated in patients with known hypersensitivity to aflibercept or any of the excipients in EYLEA HD. Hypersensitivity reactions may manifest as rash, pruritus, urticaria, severe anaphylactic/anaphylactoid reactions, or severe intraocular inflammation.

Warnings and precautions

Endophthalmitis, retinal detachments, and retinal vasculitis with or without occlusion may occur following intravitreal injections. Patients should be instructed to report any symptoms suggestive of endophthalmitis, retinal detachment, or retinal vasculitis without delay and should be managed appropriately. ( 5.1 ) Increases in intraocular pressure have been seen within 60 minutes of an intravitreal injection. ( 5.2 ) There is a potential risk of arterial thromboembolic events following intravitreal use of VEGF inhibitors.

Indications

1.1 Neovascular (Wet) Age-Related Macular Degeneration (nAMD)

1.2 Diabetic Macular Edema (DME)

1.3 Diabetic Retinopathy (DR)

1.4 Macular Edema Following Retinal Vein Occlusion (RVO)

Contraindications

Ocular or periocular infection ( 4.1 ) Active intraocular inflammation ( 4.2 ) Hypersensitivity ( 4.3 )

4.1Ocular or Periocular Infections

EYLEA HD is contraindicated in patients with ocular or periocular infections.

4.2Active Intraocular Inflammation

EYLEA HD is contraindicated in patients with active intraocular inflammation.

4.3Hypersensitivity

Warnings and precautions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary Adequate

and well-controlled studies with EYLEA HD have not been conducted in pregnant women. Aflibercept produced adverse embryofetal effects in rabbits, including external, visceral, and skeletal malformations. A fetal No Observed Adverse Effect Level (NOAEL) was not identified. At the lowest dose shown to produce adverse embryofetal effects, systemic exposure (based on AUC for free aflibercept) was approximately 0.9 -fold of the population pharmacokinetic estimated exposure in humans after an intravitreal dose of 8 mg (see Data ) .

Animal reproduction studies are not always predictive of human response, and it is not known whether EYLEA HD can cause fetal harm when administered to a pregnant woman. Based on the anti-VEGF mechanism of action for aflibercept [see Clinical Pharmacology (12.1) ] , treatment with EYLEA HD may pose a risk to human embryofetal development. EYLEA HD should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In two embryofetal development studies, aflibercept produced adverse embryofetal effects when administered every three days during organogenesis to pregnant rabbits at intravenous doses ≥3 mg per kg, or every six days during organogenesis at subcutaneous doses ≥0.1 mg per kg.

Adverse embryofetal effects included increased incidences of postimplantation loss and fetal malformations, including anasarca, umbilical hernia, diaphragmatic hernia, gastroschisis, cleft palate, ectrodactyly, intestinal atresia, spina bifida, encephalomeningocele, heart and major vessel defects, and skeletal malformations (fused vertebrae, sternebrae, and ribs; supernumerary vertebral arches and ribs; and incomplete ossification).

The maternal No Observed Adverse Effect Level (NOAEL) in these studies was 3 mg per kg. Aflibercept produced fetal malformations at all doses assessed in rabbits and the fetal NOAEL was not identified. At the lowest dose shown to produce adverse embryofetal effects in rabbits (0.1 mg per kg), systemic exposure (AUC) of free aflibercept was approximately 0.9-fold of the population pharmacokinetic estimated systemic exposure (AUC) in humans after an intravitreal dose of 8 mg.

Adverse reactions

The following potentially serious adverse reactions are described elsewhere in the labeling: Hypersensitivity [see Contraindications (4.3) ] Endophthalmitis, Retinal Detachments, and Retinal Vasculitis with or without Occlusion [see Warnings and Precautions (5.1) ] Increase in intraocular pressure [see Warnings and Precautions (5.2) ] Thromboembolic events [see Warnings and Precautions (5.3) ] The most common adverse reactions (≥3%) reported in patients treated with EYLEA HD were cataract, conjunctival hemorrhage, corneal epithelium defect, intraocular pressure increased, ocular discomfort/eye pain/eye irritation, retinal hemorrhage, vision blurred, vitreous detachment, and vitreous floaters.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Regeneron at 1-855-395-3248 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical 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 1755 patients were treated with EYLEA HD and 804 patients were treated with EYLEA 2 mg in three clinical studies. The most common adverse reactions reported in ≥3% of patients treated with EYLEA HD were cataract, conjunctival hemorrhage, corneal epithelium defect, intraocular pressure increased, ocular discomfort/eye pain/eye irritation, retinal hemorrhage, vision blurred, vitreous detachment and vitreous floaters.

Neovascular (Wet) Age-Related Macular Degeneration (AMD) and Diabetic Macular Edema (DME) The data described below reflect exposure to EYLEA HD administered every 12 weeks (HDq12), EYLEA HD administered every 16 weeks (HDq16), or EYLEA 2 mg administered every 8 weeks (2q8) in controlled clinical studies (PULSAR and PHOTON), each for 96 weeks [see Clinical Studies (14.1 , 14.2) ]. Table 1: Adverse Reactions (≥1%) in at least one group in the PULSAR or PHOTON studies Adverse Reactions PULSAR PHOTON EYLEA HDq12 EYLEA HDq16 EYLEA 2q8 EYLEA HDq12 EYLEA HDq16 EYLEA 2q8 n=335 n=338 n=336 n=328 n=163 n=167 Cataract Represents grouping of related terms 10% 10% 10% 10% 13% 7% Vision blurred 9% 9% 8% 5% 4% 6% Intraocular pressure increased 5% 4% 3% 4% 1% 5% Conjunctival hemorrhage 3% 3% 3% 5% 5% 4% Ocular discomfort/eye pain/eye irritation 3% 4% 4% 5% 4% 4% Vitreous floaters 2% 6% 5% 6% 4% 4% Vitreous detachment 2% 4% 2% 5% 3% 4% Corneal epithelium defect 3% 3% 4% 4% 9% 2% Retinal hemorrhage 5% 6% 6% 0 4% 1% Dry eye 3% 3% 5% 2% 4% 2% Intraocular inflammation 2% 1% 2% 2% 1% 1% Retinal pigment epithelial tear/epitheliopathy 2% 2% 2% 1% 0 0 Vitreous hemorrhage <1% 1% 1% 2% 3% 2% Retinal Detachment 1% 1% <1% <1% 1% 0 Foreign body sensation in eyes 1% 2% 2% <1% 1% 0 Ocular hyperemia 1% <1% 1% <1% 0 0 Retinal pigment epithelial detachment 1% 1% 3% 0 0 0 Adverse drug reactions (ADRs) reported in <1% of participants treated with EYLEA HD were lacrimation increased, eyelid edema, hypersensitivity (includes adverse events of rash, urticaria, pruritus), and injection site hemorrhage.

Macular Edema Following Retinal Vein Occlusion (RVO) The data described below reflects 36 weeks exposure to EYLEA HD administered every 8 weeks (HDq8) after 3 or 5 initial monthly doses (HDq4), or EYLEA 2 mg administered every 4 weeks (2q4) in a controlled clinical study (QUASAR). [see Clinical Studies (14.4) ] . Table 2: Most Common Adverse Reactions (≥1%) in at least one group in the QUASAR study Adverse Reactions EYLEA HDq8 following 3 initial doses (HDq4) (N=293) EYLEA HDq8 following 5 initial doses (HDq4) (N=298) EYLEA 2q4 (N=301) Intraocular pressure increased Represents grouping of related terms 7% 6% 3% Vision blurred 5% 3% 2% Conjunctival hemorrhage 3% 2% 2% Ocular discomfort/eye pain/eye irritation 3% 3% 1% Vitreous detachment 3% 3% 1% Cataract 2% 4% 3% Corneal epithelium defect 2% 2% 2% Dry eye 2% 2% 2% Vitreous floaters 1% 1% 1% Intraocular inflammation 1% <1% 1% Vitreous hemorrhage 1% 1% 0 Hypersensitivity Represents reported non-ocular adverse events of hypersensitivity, rash, urticaria and pruritus 1% 1% 1% Adverse reactions reported in <1% of the patients treated with EYLEA HD in the RVO study were foreign body sensation in eyes (includes foreign body sensation in eyes and sensation of foreign body), ocular hyperaemia (includes conjunctival hyperemia, conjunctival irritation, ocular hyperemia), retinal hemorrhage, retinal pigment epithelial detachment (includes detachment of retinal pigment epithelium), retinal pigment epithelial tear/epitheliopathy (includes retinal pigment epitheliopathy), and retinal tear.

6.2Postmarketing Experience

The following adverse reactions have been identified during postapproval use of aflibercept. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Eye disorders : Retinal vasculitis and occlusive retinal vasculitis related to intravitreal injection with aflibercept (reported at a rate of 0.6 and 0.2 per 1 million injections, respectively, based on postmarketing experience from November 2011 until November 2023).

Scleritis.

Eylea HD

Indications

Contraindications

4.1Ocular or Periocular Infections

4.2Active Intraocular Inflammation

4.3Hypersensitivity

Warnings and precautions

Two medicines in one question?

Eylea HD

Indications

Contraindications

4.1Ocular or Periocular Infections

4.2Active Intraocular Inflammation

4.3Hypersensitivity

Warnings and precautions

Two medicines in one question?

5.1Endophthalmitis, Retinal Detachments, and Retinal Vasculitis with or without Occlusion

5.2Increase in Intraocular Pressure

5.3Thromboembolic Events

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary Adequate

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Official product information

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