Wet AMD Data

PULSAR Pivotal Trial: Efficacy and Safety Results in Patients With Wet Age-Related Macular Degeneration (AMD)

In the 48-week results of the PULSAR phase 3 trial in patients with Wet AMD (N=1009), the EYLEA HD Q12W and Q16W treatment arms demonstrated noninferiority in mean change in BCVA from baseline compared with EYLEA^® (aflibercept) Injection 2 mg Q8W with fewer injections and a comparable safety profile.^1,2

EYLEA HD Was Studied in a Phase 3 Pivotal Clinical Trial of 1009 Patients With Wet AMD¹

PULSAR study design

Multicenter, randomized, double-masked study in patients with treatment-naïve Wet AMD with a mean age of 74.5 years (range: 50-96) and a mean visual acuity of ~60 ETDRS letters at baseline (range: 24-78).²

Primary endpoint

Mean change in BCVA (ETDRS letters) [noninferiority] from baseline at week 48

Key secondary endpoint

Proportion of patients without intravitreal fluid (IRF) and subretinal fluid (SRF) in the central subfield at week 16

Study Dosing Parameters for EYLEA HD Q12W and Q16W and EYLEA 2 mg Q8W¹

	Note: Figure does not reflect all dosing options once a patient is shortened.
	At week 36, patients on EYLEA HD Q16W who were previously shortened to Q12W could have been shortened to Q8W.

	Note: Figure does not reflect all dosing options once a patient is shortened.
	At week 36, patients on EYLEA HD Q16W who were previously shortened to EYLEA HD Q12W could have been shortened to EYLEA 2 mg Q8W.

EYLEA HD Met Its Primary Endpoint for Mean Change in BCVA from Baseline for Both Treatment Arms at Week 48^1,2

EYLEA HD Q12W and Q16W treatment arms demonstrated comparable ETDRS letter gains in patients with Wet AMD with fewer injections than EYLEA 2 mg Q8W^1,2*

	LS mean difference at week 48 (95% CI): EYLEA HD Q12W vs EYLEA 2 mg Q8W, -1.0 (-2.9, 0.9) letters; EYLEA HD Q16W vs EYLEA 2 mg Q8W, -1.1 (-3.0, 0.7) letters. NI margin was 4 letters.
*	Patients who completed week 48: EYLEA HD Q12W, n=316; EYLEA HD Q16W, n=312; EYLEA Q8W, n=309.
^†	Following 3 initial monthly doses. FAS at baseline. FAS, observed values (censoring data post ICE) at week 48: EYLEA HD Q12W (n=299), EYLEA HD Q16W (n=289), EYLEA 2 mg Q8W (n=285).

**Proportion of Wet AMD Patients Without Retinal Fluid in the Central Subfield* in the Combined EYLEA HD Group (Q12W and Q16W) vs EYLEA 2 mg Q8W at Week 16**¹

	Without retinal fluid defined as absence of IRF and SRF in center subfield.
*	As determined by a central reading center on Optical Coherence Tomography (OCT).
^†	Following 3 initial monthly doses.
^‡	FAS; last observation carried forward (censoring data post ICE).

Reductions in Central Retinal Thickness From Baseline in EYLEA HD Q12W and Q16W Treatment Arms vs EYLEA 2 mg Q8W at Week 48¹*

Mean change in CRT from baseline through week 48 (additional secondary endpoint)¹

*	Reductions in CRT were determined by a central reading center on OCT. FAS at baseline. FAS; observed values (censoring data post ICE) at week 48: EYLEA HD Q12W (n=289), EYLEA HD Q16W (n=282), EYLEA 2 mg Q8W (n=273).
^†	Patients who completed week 48: EYLEA HD Q12W (n=336), EYLEA HD Q16W (n=312), EYLEA 2 mg Q8W (n=309).
^‡	Following 3 initial monthly doses.

EYLEA HD Dosing Frequency Results: 83% of Patients With Wet AMD in the Combined EYLEA HD Group Maintained Dosing Intervals ≥Q12W Through Week 48¹*

Proportion of patients maintaining Q12W and Q16W dosing intervals through week 48

*	Following 3 initial monthly doses.
^†	Patients completing week 48.
^‡	Patients who met DRM criteria for interval shortening.
^§	Patients completing week 48: EYLEA HD Q12W n=316; EYLEA HD Q16W n=312; EYLEA Q8W n=309.
	Values do not total 100% due to rounding.

Safety Profile of EYLEA HD Was Consistent With the Established Profile of EYLEA 2 mg Through Week 48^2,3

*	After 3 initial monthly doses.
^†	Represents grouping of related terms.
	Adverse drug reactions (ADRs) reported in <1% of participants treated with EYLEA HD were ocular hyperemia (includes adverse events of conjunctival hyperemia, conjunctival irritation, ocular hyperemia), lacrimation increased, eyelid edema, hypersensitivity (includes adverse events of rash, urticaria, pruritus), retinal tear, and injection site hemorrhage.²
	No cases of endophthalmitis or occlusive retinal vasculitis were reported through week 48.¹
	SELECT IMPORTANT SAFETY INFORMATION FOR EYLEA HD AND EYLEA (aflibercept) Injection 2 mg
	WARNINGS AND PRECAUTIONS
	Endophthalmitis, Retinal Detachments, and Retinal Vasculitis With or Without Occlusion: Intravitreal injections, including those with aflibercept, have been associated with endophthalmitis and retinal detachments and, more rarely, retinal vasculitis with or without occlusion. Proper aseptic injection technique must always be used when administering EYLEA HD or EYLEA. Patients and/or caregivers should be instructed to report any signs and/or symptoms suggestive of endophthalmitis, retinal detachment, or retinal vasculitis without delay and should be managed appropriately.

IMPORTANT SAFETY INFORMATION FOR EYLEA HD AND EYLEA (aflibercept) Injection 2 mg

CONTRAINDICATIONS

EYLEA HD and EYLEA are contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in EYLEA HD or EYLEA.

WARNINGS AND PRECAUTIONS

Intravitreal injections, including those with aflibercept, have been associated with endophthalmitis and retinal detachments and, more rarely, retinal vasculitis with or without occlusion. Proper aseptic injection technique must always be used when administering EYLEA HD or EYLEA. Patients and/or caregivers should be instructed to report any signs and/or symptoms suggestive of endophthalmitis, retinal detachment, or retinal vasculitis without delay and should be managed appropriately.
Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA HD and EYLEA. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with VEGF inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately.
There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including EYLEA HD and EYLEA. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).
- EYLEA HD: The incidence of reported thromboembolic events in the wet AMD study (PULSAR) from baseline through week 48 was 0.4% (3 out of 673) in the combined group of patients treated with EYLEA HD compared with 1.5% (5 out of 336) in patients treated with EYLEA 2 mg. The incidence in the DME study (PHOTON) from baseline to week 48 was 3.1% (15 out of 491) in the combined group of patients treated with EYLEA HD compared with 3.6% (6 out of 167) in patients treated with EYLEA 2 mg.
- EYLEA: The incidence of reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients treated with EYLEA compared with 1.5% (9 out of 595) in patients treated with ranibizumab; through 96 weeks, the incidence was 3.3% (60 out of 1824) in the EYLEA group compared with 3.2% (19 out of 595) in the ranibizumab group. The incidence in the DME studies from baseline to week 52 was 3.3% (19 out of 578) in the combined group of patients treated with EYLEA compared with 2.8% (8 out of 287) in the control group; from baseline to week 100, the incidence was 6.4% (37 out of 578) in the combined group of patients treated with EYLEA compared with 4.2% (12 out of 287) in the control group. There were no reported thromboembolic events in the patients treated with EYLEA in the first six months of the RVO studies.

ADVERSE REACTIONS

EYLEA HD:
- The most common adverse reactions (≥3%) reported in patients receiving EYLEA HD were cataract, conjunctival hemorrhage, intraocular pressure increased, ocular discomfort/eye pain/eye irritation, vision blurred, vitreous floaters, vitreous detachment, corneal epithelium defect, and retinal hemorrhage.
EYLEA:
- 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.
Patients may experience temporary visual disturbances after an intravitreal injection with EYLEA HD or EYLEA and the associated eye examinations. Advise patients not to drive or use machinery until visual function has recovered sufficiently.

INDICATIONS

EYLEA^® HD (aflibercept) Injection 8 mg is indicated for the treatment of patients with Neovascular (Wet) Age-Related Macular Degeneration (AMD), Diabetic Macular Edema (DME), and Diabetic Retinopathy (DR).

EYLEA^® (aflibercept) Injection 2 mg is indicated for the treatment of patients with Neovascular (Wet) Age-Related Macular Degeneration (AMD), Macular Edema following Retinal Vein Occlusion (RVO), Diabetic Macular Edema (DME), and Diabetic Retinopathy (DR).

Please see full Prescribing Information for EYLEA HD and EYLEA.

BCVA = best corrected visual acuity; CRT = central retinal thickness; ETDRS = Early Treatment Diabetic Retinopathy Study; FAS = full analysis set; ICE = intercurrent events; LS = least squares; NI = noninferiority; Q8W = every 8 weeks; Q12W = every 12 weeks; ≥Q12W = more than or equal to every 12 weeks; Q16W = every 16 weeks.

References: 1. Brown DM; PULSAR Study Investigators. Aflibercept 8 mg in patients with nAMD: 48-week results from the phase 3 PULSAR trial. Presented at: Angiogenesis, Exudation, and Degeneration 2023; February 11, 2023. 2. EYLEA HD full U.S. Prescribing Information. Regeneron Pharmaceuticals, Inc. December 2023. 3. EYLEA full U.S. Prescribing Information. Regeneron Pharmaceuticals, Inc. December 2023.

01/2024
US.EHD.23.12.0053

Wet AMD Data

PULSAR Pivotal Trial: Efficacy and Safety Results in Patients With Wet Age-Related Macular Degeneration (AMD)

EYLEA HD Was Studied in a Phase 3 Pivotal Clinical Trial of 1009 Patients With Wet AMD1

Primary endpoint

Key secondary endpoint

Study Dosing Parameters for EYLEA HD Q12W and Q16W and EYLEA 2 mg Q8W1

EYLEA HD Met Its Primary Endpoint for Mean Change in BCVA from Baseline for Both Treatment Arms at Week 481,2

EYLEA HD Q12W and Q16W treatment arms demonstrated comparable ETDRS letter gains in patients with Wet AMD with fewer injections than EYLEA 2 mg Q8W1,2*

Proportion of Wet AMD Patients Without Retinal Fluid in the Central Subfield* in the Combined EYLEA HD Group (Q12W and Q16W) vs EYLEA 2 mg Q8W at Week 161

Reductions in Central Retinal Thickness From Baseline in EYLEA HD Q12W and Q16W Treatment Arms vs EYLEA 2 mg Q8W at Week 481*

Mean change in CRT from baseline through week 48 (additional secondary endpoint)1

EYLEA HD Dosing Frequency Results: 83% of Patients With Wet AMD in the Combined EYLEA HD Group Maintained Dosing Intervals ≥Q12W Through Week 481*

Proportion of patients maintaining Q12W and Q16W dosing intervals through week 48

Safety Profile of EYLEA HD Was Consistent With the Established Profile of EYLEA 2 mg Through Week 482,3

No cases of endophthalmitis or occlusive retinal vasculitis were reported through week 48.1

SELECT IMPORTANT SAFETY INFORMATION FOR EYLEA HD AND EYLEA (aflibercept) Injection 2 mg

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